Methods of assessing citrullination and activity of pad4 modulators

Abstract

The present application relates to methods for quantifying citrullination and methods that may be used to assess the activity of agents including PAD4 (peptidyl arginine deiminase 4) modulators, such as small molecules or antibodies, for example. In certain embodiments, the methods comprise assessing citrullination of one or more citrullination sites on a protein or a peptide fragment thereof present in a biological sample.

Description

METHODS OF ASSESSING CITRULLINATION AND ACTIVITY OF PAD4 MODULATORSFIELDThe present application relates to methods involving assessing citrullination of a citrullination site on a protein or peptide fragment thereof that is present in a biological sample from a subject. The methods may be used for, inter alia, assessing the citrullination modifying activity of agents including PALM (peptidyl arginine deiminase 4) modulators, such as small molecules or antibodies, for example.BACKGROUNDPALM (peptidyl arginine deiminase 4) is the dominant PAD enzyme found in synovial tissues of subjects with rheumatoid arthritis (RA), and is also associated with other autoimmune diseases, such as lupus, lupus nephritis, vasculitis, thrombosis (e.g., venous thrombosis), inflammatory bowel disease (IBD), and others. PAD4 is an enzyme that catalyzes the conversion of arginine to citrulline. About 15% of RA patients have antibodies that activate PAD4, and presence of such PAD4-activating antibodies correlates with severe joint erosive disease. Compounds capable of modulating the activity of PAD4 may be useful in treating various conditions. For example, PAD4 inhibitors may be useful for treating autoimmune diseases, such as RA and others.Accordingly, methods for assessing the activity of PAD4 modulators are useful, for example, for monitoring treatment with existing PAD4 modulators and for assessing novel PAD4 modulators in development, among other uses.SUMMARYThe present disclosure provides methods of assessing citrullination of proteins or peptides, and methods of assessing the activity of PAD4 modulators or other therapeutic agents that can affect citrullination, by assessing citrullination of one or more citrullination sites on a protein or a peptide fragment thereof present in a biological sample.The present disclosure relates, inter alia, to embodiments including the following, for example:1. A method of determining citrullination of a protein or peptide fragment thereof, comprising assessing citrullination of a citrullination site on a protein or a peptide fragmentthereof in a biological sample from a subject, wherein the biological sample has been exposed to a PAD4 inhibitor, wherein the citrullination site is selected from one or more of the following:R1391 of proteoglycan 4 (corresponding to R1391 of Q92954),R573 of fibrinogen alpha chain (corresponding to R573 of P02671),R591 of fibrinogen alpha chain (corresponding to R591 of P02671),R573 of complement C3 (corresponding to R573 of PO 1024),R748 of complement C3 (corresponding to R748 of PO 1024),R688 of inter-alpha-trypsin inhibitor heavy chain H4 (corresponding to R688 ofQI 4624),R297 of alpha- 1-microglobulin / bikunin precursor (corresponding to R297 of P02760), R715 of alpha-2-macroglobulin (corresponding to R715 of PO 1023),R32 of gel solin (corresponding to R32 of P06396),R59 of haptoglobin (corresponding to R59 of P00738), andR651 of serotransferrin (corresponding to R651 ofP02787).2. A method of assessing the activity of a PAD4 inhibitor, the method comprising assessing citrullination of a citrullination site on a protein or a peptide fragment thereof that is present in a biological sample from a subject, wherein the biological sample has been exposed to the PAD4 inhibitor, wherein the citrullination site is selected from one or more of the following:R1391 of proteoglycan 4 (corresponding to R1391 of Q92954),R573 of fibrinogen alpha chain (corresponding to R573 of P02671),R591 of fibrinogen alpha chain (corresponding to R591 of P02671),R573 of complement C3 (corresponding to R573 of PO 1024),R748 of complement C3 (corresponding to R748 of PO 1024),R688 of inter-alpha-trypsin inhibitor heavy chain H4 (corresponding to R688 ofQI 4624),R297 of alpha- 1-microglobulin / bikunin precursor (corresponding to R297 of P02760), R715 of alpha-2-macroglobulin (corresponding to R715 of P01023),R32 of gel solin (corresponding to R32 of P06396),R59 of haptoglobin (corresponding to R59 of P00738), andR651 of serotransferrin (corresponding to R651 ofP02787).3. The method of embodiment 2, wherein the PAD4 inhibitor reduces citrullination at the citrullination site in a dose-dependent manner.4. The method of embodiment 1, 2, or 3, wherein the method comprises assessing citrullination of a peptide fragment of the protein, wherein the peptide fragment comprises the citrullination site.5. The method of any one of embodiments 1-4, wherein the biological sample has been exposed to a PAD inhibitor in vivo in a subject as a result of the PAD inhibitor being administered to the subject.6. The method of any one of embodiments 1-4, wherein the biological sample has been exposed to the PAD inhibitor by contacting the biological sample with the PAD inhibitor ex vivo.7. The method of any one of embodiments 1-6, wherein the assessing citrullination of the citrullination site comprises mass spectrometry (MS).8. The method of any one of embodiments 1-6, wherein the assessing citrullination of the citrullination site comprises liquid chromatography and mass spectrometry (LC-MS).9. The method of any one of embodiments 1-6, wherein the assessing citrullination comprises selective reaction monitoring and chromatographic separation.10. The method of any one of embodiments 1-9, wherein assessing citrullination of the citrullination site comprises measuring, in the biological sample, a first concentration of the citrullinated protein or peptide fragment thereof and a second concentration of corresponding total protein.11. The method of embodiment 10, wherein assessing citrullination of the citrullination site comprises determining a citrullination ratio, wherein the citrullination ratio is a ratio of the first concentration to the second concentration.12. The method of embodiment 11, wherein the method comprises comparing the citrullination ratio to a reference citrullination ratio.13. The method of embodiment 12, wherein the reference citrullination ratio is a citrullination ratio determined for a control biological sample.14. The method of embodiment 13, wherein the control biological sample is a biological sample that: (a) has not been exposed to a PAD4 modulator or PAD4 inhibitor, (b) is from the same subject, and / or (c) is from the same subject prior to treatment with the PAD4 inhibitor.15. The method of any one of embodiments 12-14, wherein the assessing comprises determining a difference between the citrullination ratio for the biological sample and the reference citrullination ratio.16. The method of any one of embodiments 1-15, wherein the method comprises contacting the biological sample with exogenous PAD4.17. A method comprising:(i) contacting a biological sample from a subject with exogenous PAD4, and(ii) assessing citrullination of a citrullination site on a protein or a peptide fragment thereof that is present in a biological sample; wherein the citrullination site is selected from one or more of the following:R1391 of proteoglycan 4 (corresponding to R1391 of Q92954),R573 of fibrinogen alpha chain (corresponding to R573 of P02671),R591 of fibrinogen alpha chain (corresponding to R591 of P02671),R573 of complement C3 (corresponding to R573 of PO 1024),R748 of complement C3 (corresponding to R748 of PO 1024),R688 of inter-alpha-trypsin inhibitor heavy chain H4 (corresponding to R688 ofQI 4624),R297 of alpha- 1-microglobulin / bikunin precursor (corresponding to R297 of P02760),R715 of alpha-2-macroglobulin (corresponding to R715 of PO 1023),R32 of gel solin (corresponding to R32 of P06396),R59 of haptoglobin (corresponding to R59 of P00738), andR651 of serotransferrin (corresponding to R651 ofP02787).18. The method of embodiment 16 or 17, wherein the method comprises incubating the exogenous PALM with the biological sample.19. The method of embodiment 18, wherein the method comprises incubating the exogenous PALM with the biological sample at a temperature of 36-38 °C.20. The method of embodiment 18 or 19, wherein the incubating is for 1-3 hours.21. The method of any one of embodiments 18-20, wherein the method comprises adding EDTA to the biological sample after the incubation with exogenous PALM.22. The method of any one of embodiments 1-21, wherein the method comprises incubating the biological sample for an incubation period before assessing citrullination.23. The method of embodiment 22, wherein the incubating is performed at 35-40°C.24. The method of embodiment 22 or 23, wherein the incubation period is 48 to 96 hours.25. The method of any one of embodiments 1-24, comprising preparing the biological sample for assessment prior to the assessing.26. The method of embodiment 25, wherein the preparing comprises enzymatically digesting proteins in the biological sample to form peptide fragments thereof.27. The method of embodiment 25 or 26, wherein the preparing comprises depleting proteins or peptide fragments thereof from the biological sample that are not targeted by the assessing.28. The method of any one of embodiments 25-27, wherein the preparing comprises diluting the biological sample.29. The method of any one of embodiments 25-28, wherein the preparing comprises denaturing proteins or peptide fragments thereof in the biological sample.30. The method of any one of embodiments 25-29, wherein the preparing comprises enriching the biological sample for a protein or peptide fragment thereof that comprises the citrullination site to be assessed.31. The method of embodiment 30, wherein the preparing comprises contacting the biological sample with an antibody that specifically binds to citrullinated and noncitrullinated forms of the protein or peptide fragment thereof that comprises the citrullination site to be assessed.32. The method of any one of embodiments 1-31, wherein the method comprises freezing and thawing the biological sample before assessing citrullination of the citrullination site.33. The method of any one of embodiments 1-32, comprising:(a) immunoenriching the sample for the protein or peptide fragment thereof to form an immunoenriched sample, wherein the immunoenriching comprises contacting the sample with an antibody that binds to both citrullinated and noncitrullinated forms of the protein and / or to both citrullinated and noncitrullinated forms of the peptide fragment thereof comprising the citrullination site,(b) enzymatically digesting proteins in the sample either before or after the immunoenriching to form the peptide fragment, and(c) assessing citrullination of the peptide fragment at the citrullination site.34. The method of embodiment 33, wherein the immunoenriching comprises contacting the sample with an immobilized antibody that binds to both citrullinated and noncitrullinated forms of the protein and / or to both citrullinated and noncitrullinated forms of the peptide fragment thereof comprising the citrullination site, and eluting protein and / or peptide bound to the immobilized antibody.35. The method of embodiment 33 or 34, wherein the enzymatically digesting is conducted before the immunoenriching.36. The method of embodiment 33 or 34, wherein the enzymatically digesting is conducted after the immunoenriching.37. The method of any one of embodiments 33-36, wherein the immunoenriching comprises incubating the sample with the immobilized antibody for at least 30 minutes.38. The method of embodiment 37, wherein the incubating is at a temperature of 22-28°C.39. The method of embodiment 37 or 38, wherein the incubating is for a period of 30 to 90 minutes.40. The method of any one of embodiments 33-38, wherein the immunoenriching comprises shaking during the incubating.41. The method of any one of embodiments 34-40, wherein the immunoenriching comprises removing the immobilized antibody from the sample and washing the immobilized antibody prior to the eluting.42. The method of any one of embodiments 34-41, wherein the eluting comprises washing the immobilized antibody with an elution composition under acidic conditions.43. The method of embodiment 42, wherein the elution composition comprises a detergent.44. The method of embodiment 43, wherein the detergent is a zwitterionic detergent.45. The method of any one of embodiments 34-44, the method comprises neutralizing eluted protein in a buffer prior to assessing, and optionally prior to enzymatically digesting.46. The method of any one of embodiments 33-45, wherein the antibody is immobilized by attachment to a solid surface.47. The method of any one of embodiments 33-46, wherein the assessing citrullination comprises measuring a first concentration of citrullinated peptide in the digested peptides and a second concentration of signature peptide in the digested peptides, and optionally determining a citrullination ratio, wherein the citrullination ratio is a ratio of the first concentration to the second concentration.48. The method of any one of embodiments 33-47, comprising denaturing proteins in the immunoenriched sample prior to the assessing.49. The method of any one of embodiments 34-48, comprising denaturing the eluted protein prior to the assessing.50. The method of embodiment 49, comprising denaturing the eluted protein prior to enzymatically digesting the eluted protein.51. The method of any one of embodiments 33-50, comprising diluting the plasma or serum sample prior to the immunoenriching and performing the immunoenriching on the sample that has been diluted.52. The method of embodiment 51, comprising diluting the plasma or serum sample by 2 to 1000 fold.53. The method of embodiment 51 or 52, wherein the sample that has been diluted has a volume of at least 5 pl.54. The method of any one of embodiments 1-53, wherein the sequence of the peptide fragment comprises one of the following sequences, wherein the citrullination site is designated by underlining: AITTRSGQTLSK (SEQ ID NO: 247), ESSSHHPGIAEFPSRGK (SEQ ID NO: 248), QFTSSTSYNRGDSTFESK (SEQ ID NO: 249), SGQSEDRQPVPGQQMTLK (SEQ ID NO: 250), ASHLGLARSNLDEDIIAEENIVSR (SEQ ID NO: 251), QLGLPGPPDVPDHAAYHPFRR (SEQ ID NO: 252), GPCRAFIQLWAFDAVK (SEQ ID NO: 253), VGFYESDVMGRGHAR (SEQ ID NO: 254), ATASRGASQAGAPQGR (SEQ ID NO: 255), LRTEGDGVYTLNDK (SEQ ID NO: 256), and DLLFRDDTVCLAK (SEQ ID NO: 257).55. The method of any one of embodiments 1-54, wherein the biological sample comprises whole blood, plasma, serum, or blood supernatant.56. The method of embodiment 55, wherein the citrullination site is: R1391 of proteoglycan 4 (corresponding to R1391 of Q92954), R573 of fibrinogen alpha chain (corresponding to R573 of P02671), or R591 of fibrinogen alpha chain (corresponding to R591 of P02671), at R591 ofP02671 or R593 ofP02671.57. The method of embodiment 56, wherein the peptide fragment comprises the amino acid sequence of AITTRSGQTLSK (SEQ ID NO: 247), ESSSHHPGIAEFPSRGK (SEQ ID NO: 248), or QFTSSTSYNRGDSTFESK (SEQ ID NO: 249), wherein the underlined R is the citrullination site.58. The method of any one of embodiments 1-54, wherein the biological sample comprises synovial fluid.59. The method of embodiment 58, wherein the citrullination site is: R1391 of proteoglycan 4 (corresponding to R1391 of Q92954), R573 of fibrinogen alpha chain (corresponding to R573 of P02671), R591 of fibrinogen alpha chain (corresponding to R591 of P02671), at R591 ofP02671 or R593 ofP02671, R573 of complement C3 (corresponding to R573 of P01024), R688 of inter-alpha-trypsin inhibitor heavy chain H4 (corresponding to R688 ofQI 4624), or R297 of alpha- 1-microglobulin / bikunin precursor (corresponding to R297 of P02760).60. The method of embodiment 59, wherein the sequence of the peptide fragment comprises one of the following sequences, wherein the citrullination site is designated by underlining: AITTRSGQTLSK (SEQ ID NO: 247), ESSSHHPGIAEFPSRGK (SEQ ID NO: 248), QFTSSTSYNRGDSTFESK (SEQ ID NO: 249), SGQSEDRQPVPGQQMTLK (SEQ ID NO: 250), QLGLPGPPDVPDHAAYHPFRR (SEQ ID NO: 252), and GPCRAFIQLWAFDAVK (SEQ ID NO: 253).61. The method of any one of embodiments 1-60, wherein the method comprises assessing citrullination of two or more proteins or peptide fragments thereof.62. The method of any one of embodiments 1-60, wherein the method further comprises assessing citrullination of at least one additional citrullination site listed in Table A or in any one of Tables 3-18.63. A method comprising:(a) immunoenriching a biological sample for a protein of interest to form an immunoenriched sample, wherein the immunoenriching comprises contacting the sample with an antibody that specifically binds to both citrullinated and noncitrullinated forms of the protein of interest or that specifically binds to both citrullinated and noncitrullinated forms of a peptide fragment of the protein of interest, the protein of interest or peptide fragment comprising a citrullination site, and(b) assessing citrullination in the immunoenriched sample at the citrullination site.64. A method comprising:(a) immunoenriching a biological sample for a protein of interest to form an immunoenriched sample, wherein the immunoenriching comprises contacting the sample with an antibody that binds to both citrullinated and noncitrullinated forms of the protein of interest or that specifically binds to both citrullinated and noncitrullinated forms of a peptide fragment of the protein of interest, the protein of interest or the peptide fragment comprising a citrullination site,(b) enzymatically digesting the immunoenriched sample to form peptide fragments of the protein of interest, wherein parts (a) and (b) may be performed in any order, and(c) assessing citrullination of the peptide fragments at the citrullination site.65. A method comprising(a) immunoenriching a biological sample by contacting the sample with an immobilized antibody that binds to both citrullinated and noncitrullinated forms of a protein of interest, the protein of interest comprising a citrullination site,(b) eluting protein bound to the immobilized antibody,(d) enzymatically digesting the eluted protein to form peptide fragments thereof, and(e) assessing citrullination of the peptide fragments at the citrullination site.66. A method comprising(a) enzymatically digesting proteins in a biological sample to form peptide fragments thereof,(b) immunoenriching the enzymatically digested biological sample by contacting the sample with an immobilized antibody that specifically binds to both citrullinated and noncitrullinated forms of a peptide fragment of a protein of interest, the peptide fragment comprising a citrullination site,(c) eluting peptides bound to the immobilized antibody, and(d) assessing citrullination of the peptides at the citrullination site.67. The method of any one of embodiments 63-66, wherein the sample comprises whole blood, plasma, serum, or blood supernatant.68. A method of assessing the activity of a PAD4 inhibitor, the method comprising(a) obtaining a biological sample from a subject following treatment of the subject with at least one dose of a PAD4 inhibitor, and(b) assessing citrullination of a citrullination site on a protein or a peptide fragment thereof that is present in the biological sample.69. An in vitro method of assessing the activity of a PAD4 inhibitor, the method comprising(a) treating a biological sample from a subject with a PAD4 inhibitor to form a treated biological sample, and after the treating,(b) assessing citrullination of a citrullination site on a protein or a peptide fragment thereof that is present in the biological sample.70. An in vitro method of assessing the activity of a PAD4 inhibitor, the method comprising(i) dividing a biological sample obtained from a subject into a plurality of biological samples,(ii) contacting each of the plurality of biological samples with a different dose of the PAD4 inhibitor, and(iii) assessing, for each of the plurality of biological samples, citrullination of a PAD4-dependent citrullination site on a protein or peptide fragment thereof that is present in the biological sample.71. The method of embodiment 70, further comprising calculating an IC50 for the PAD4 inhibitor based on the outcome of the assessing.72. The method of any one of embodiments 68 or 70-71, further comprising selecting or adjusting a dose of a PALM inhibitor to be administered to the subject based on the outcome of the assessing.73. An in vitro method of assessing citrullination by endogenous PALM, the method comprising(a) incubating a whole blood sample from a subject at 35-40°C for an incubation period,(b) after the incubation period, separating plasma or supernatant from the whole blood sample, and(c) assessing citrullination of a citrullination site on a protein or peptide fragment thereof that is present in the plasma or supernatant.74. An in vitro method of assessing changes in citrullination in a subject, the method comprising(a) incubating a whole blood sample from a subject at 35-40°C for an incubation period, wherein the sample is obtained from the subject following administration of a PALM inhibitor to the subj ect,(b) after the incubation period, separating plasma or supernatant from the whole blood sample, and(c) assessing citrullination of a citrullination site on a protein or peptide fragment thereof that is present in the plasma or supernatant.75. The method of embodiment 74, further comprising(d) incubating a second whole blood sample from the subject at 35-40°C for an incubation period, wherein the second whole blood sample is obtained from the subject before administration of the PALM inhibitor to the subject,(e) after the incubation period, separating plasma or supernatant from the second whole blood sample, and(f) assessing citrullination of a citrullination site on a protein or peptide fragment thereof that is present in the plasma or supernatant from the second whole blood sample.76. The method of embodiment 74, further comprising comparing an outcome of the assessing in step (f) with an outcome of the assessing in step (c).77. A method of assessing effects of a PAD4 inhibitor, the method comprising(a) exposing a whole blood sample from a subject to a PAD4 inhibitor in vitro,(b) incubating the whole blood sample at 35-40°C for an incubation period,(c) after the incubation period, separating plasma or supernatant from the whole blood sample, and(d) assessing citrullination of a citrullination site on a protein or peptide fragment thereof that is present in the plasma or supernatant.78. The method of embodiment 75, further comprising(e) incubating a control whole blood sample at 35-40°C for an incubation period,(f) after the incubation period, separating control plasma or supernatant from the control whole blood sample, and(g) assessing citrullination of a citrullination site on a protein or peptide fragment thereof that is present in the control plasma or supernatant.79. The method of embodiment 78, further comprising comparing an outcome of the assessing in step (g) with an outcome of the assessing in step (d).80. An in vitro method of assessing PAD4-dependent citrullination, the method comprising assessing citrullination of a citrullination site on a protein or peptide fragment thereof that is present in plasma or supernatant that has been separated from a whole blood sample that has been incubated at 35-40°C for an incubation period.81. The method of embodiment 88, wherein the plasma or supernatant has been frozen and the method comprises thawing the plasma or supernatant prior to the assessing.82. A method of assessing citrullination at a citrullination site, the method comprising(i) measuring a first concentration of a citrullinated protein or a citrullinated peptide in a biological sample by mass spectrometry (MS), wherein the citrullinated protein or citrullinated peptide is citrullinated at a citrullination site, and(ii) measuring a second concentration of corresponding total protein in the biological sample by MS.83. The method of embodiment 82, wherein the method comprises (i) measuring a first concentration of a citrullinated peptide from a target protein in a biological sample by MS, wherein the citrullinated peptide is citrullinated at a citrullination site, and (ii) measuring the second concentration by measuring the concentration of a signature peptide from the target protein in the biological sample by MS.84. The method of embodiment 82 or 83, further comprising calculating a ratio of the first concentration to the second concentration85. The method of any one of embodiments 82-84, wherein the method comprises measuring the first concentration and the second concentration for each of a plurality of different proteins or peptides.86. The method of embodiment 85, wherein the method comprises measuring the first concentration for each of two different peptides, each of which are nonoverlapping fragments of the same protein and contain different citrullination sites.87. The method of embodiment 85 or 86, wherein the method comprises calculating a ratio of the first concentration to the second concentration for each of the plurality of different proteins or peptides.88. The method of any one of embodiments 63-87, wherein the citrullination site a site listed in Table A or in any one of Tables 3-18.89. The method of any one of embodiments 63-88, wherein the citrullination site is selected from one or more of the following:R1391 of proteoglycan 4 (corresponding to R1391 of Q92954),R573 of fibrinogen alpha chain (corresponding to R573 of P02671), R591 of fibrinogen alpha chain (corresponding to R591 of P02671), R573 of complement C3 (corresponding to R573 of PO 1024), R748 of complement C3 (corresponding to R748 of PO 1024),R688 of inter-alpha-trypsin inhibitor heavy chain H4 (corresponding to R688 of QI 4624),R297 of alpha- 1-microglobulin / bikunin precursor (corresponding to R297 of P02760), R715 of alpha-2-macroglobulin (corresponding to R715 of PO 1023), R32 of gel solin (corresponding to R32 of P06396),R59 of haptoglobin (corresponding to R59 of P00738), andR651 of serotransferrin (corresponding to R651 ofP02787).90. The method of embodiment 89, wherein the method comprises assessing citrullination at one of the following peptide sequences, wherein the citrullination site is designated by underlining: AITTRSGQTLSK (SEQ ID NO: 247), ESSSHHPGIAEFPSRGK (SEQ ID NO: 248), QFTSSTSYNRGDSTFESK (SEQ ID NO: 249), SGQSEDRQPVPGQQMTLK (SEQ ID NO: 250), ASHLGLARSNLDEDIIAEENIVSR (SEQ ID NO: 251), QLGLPGPPDVPDHAAYHPFRR (SEQ ID NO: 252), GPCRAFIQLWAFDAVK (SEQ IDNO: 253), VGFYESDVMGRGHAR (SEQ ID NO: 254), ATASRGASQAGAPQGR (SEQ ID NO: 255), LRTEGDGVYTLNDK (SEQ ID NO: 256), and DLLFRDDTVCLAK (SEQ ID NO: 257).91. The method of any one of embodiments 1-90, wherein the biological sample is obtained from a subject that is ACPA positive.92 The method of any one of embodiments 1-91, wherein the biological sample is obtained from a subject that is positive for endogenous PAD4 antibodies.93. The method of embodiment 92, wherein the subject is positive for endogenous PAD4 activating antibodies.94. The method of any one of embodiments 1-93, wherein the biological sample is obtained from a subject that has been diagnosed with a citrullinati on-related disease or is at risk for developing a citrullination-related disease.95. The method of any one of embodiments 1-94, wherein the method further comprises selecting the subject from which the biological sample was derived for treatment of a citrullination-related disease based on the outcome of the assessing.96. The method of embodiment 95, wherein the citrullination-related disease is an autoimmune disorder.97. The method of embodiment 96, wherein the citrullination-related disease is rheumatoid arthritis, lupus (e.g., systemic lupus erythematosus (SLE)), lupus nephritis, vasculitis (e.g., ANCA-associated vasculitis), thrombosis (e.g, venous thrombosis), or inflammatory bowel disease (IBD) (e.g., ulcerative colitis, Crohn’s disease).98. The method of any one of embodiments 1-97, wherein the biological sample is obtained from a subject following treatment of the subject with at least one dose of a PAD4 inhibitor.99. The method of any one of embodiments 1-98, wherein the biological sample is obtained from a subject that is a normal, healthy subject.100. The method of any one of claims 1-99, wherein the method further comprises administering a PAD4 inhibitor to the subject, and optionally assessing citrullinati on of a citrullinati on site on a protein or peptide fragment thereof in a sample from the subject collected following administering of the PAD4 inhibitorAdditional exemplary embodiments of the disclosure include the following:1. A method of assessing the activity of a PAD4 modulator, the method comprising assessing citrullination of a citrullination site on a protein or a peptide fragment thereof that is present in a biological sample from a subject, wherein the biological sample has been exposed to aPAD4 modulator, wherein the protein is selected from one or more of: alpha-2-HS- glycoprotein, alpha-2-macroglobulin, albumin, antithrombin-III, apolipoprotein A-I, apolipoprotein A-IV, apolipoprotein B-100, apolipoprotein E, apolipoprotein LI, C4b- binding protein alpha chain, ceruloplasmin, clusterin, complement C2, complement C3, complement C4-A, complement C4-B, complement factor B, complement factor H, complement factor I, complement component C9, fibrinogen alpha chain, fibrinogen beta chain, fibrinogen gamma chain, fibronectin, galectin-3 -binding protein, gelsolin, haptoglobin, haptoglobin-related protein, hemopexin, immunoglobulin heavy variable 1-3, immunoglobulin heavy variable 1-8, immunoglobulin heavy variable 1-46, immunoglobulin heavy variable 1-69, immunoglobulin heavy variable 1-69D, inter-alpha-trypsin inhibitor heavy chain H4, immunoglobulin lambda-like polypeptide 1, immunoglobulin heavy constant mu, inter-alpha-trypsin inhibitor heavy chain H2, isoform 2 of complement C4-A, plasminogen, plasminogen-like protein A, alpha- 1-microglobulin / bikunin precursor (protein AMBP), prothrombin, proteoglycan 4, serotransferrin, serum amyloid A-l protein, serum amyloid A-2 protein, serum amyloid A-4 protein, stromelysin- 1, vitamin D-binding protein, and vitronectin.2. The method of embodiment 1, wherein the PAD4 modulator is a PAD4 inhibitor.3. The method of embodiment 1 or 2, wherein the citrullination site is selected from one or more citrullination sites shown in Table A or Tables 3-18.4. The method of embodiment 3, the method comprising assessing citrullination of a peptide fragment, wherein the sequence of the peptide fragment comprises a peptide sequence shown in Tables 3-18.5. The method of embodiment 1 or 2, wherein the citrullination site is selected from one or more of the following:R1391 of proteoglycan 4 (corresponding to R1391 of Q92954), R573 of fibrinogen alpha chain (corresponding to R573 of P02671), R591 of fibrinogen alpha chain (corresponding to R591 of P02671), R573 of complement C3 (corresponding to R573 of PO 1024), R748 of complement C3 (corresponding to R573 of PO 1024), R688 of inter-alpha-trypsin inhibitor heavy chain H4 (corresponding to R688 of QI 4624),R297 of alpha- 1-microglobulin / bikunin precursor (corresponding to R297 of P02760), R715 of alpha-2-macroglobulin (corresponding to R715 of PO 1023),R32 of gel solin (corresponding to R32 of P06396),R59 of haptoglobin (corresponding to R59 of P00738), and R651 of serotransferrin (corresponding to R651 ofP02787).6. The method of any one of embodiments 1 to 4, the method comprising assessing citrullination of a peptide fragment, wherein the sequence of the peptide fragment comprises one of the following sequences, wherein the citrullination site is designated by underlining: AITTRSGQTLSK (SEQ ID NO: 247), ESSSHHPGIAEFPSRGK (SEQ ID NO: 248), QFTSSTSYNRGDSTFESK (SEQ ID NO: 249), SGQSEDRQPVPGQQMTLK (SEQ ID NO: 250), ASHLGLARSNLDEDIIAEENIVSR (SEQ ID NO: 251), QLGLPGPPDVPDHAAYHPFRR (SEQ ID NO: 252), GPCRAFIQLWAFDAVK (SEQ ID NO: 253), VGFYESDVMGRGHAR (SEQ ID NO: 254), ATASRGASQAGAPQGR (SEQ ID NO: 255), LRTEGDGVYTLNDK (SEQ ID NO: 256), and DLLFRDDTVCLAK (SEQ ID NO: 257).7. The method of any one of embodiments 1 to 6, wherein the biological sample has been exposed to a PAD4 modulator in vivo in a subject as a result of the PAD4 modulator being administered to the subject.8. The method of any one of embodiments 1 to 7, wherein the biological sample comprises synovial fluid.9. The method of embodiment 8, wherein the citrullination site is selected from one or more citrullination sites shown in Table 11 and / or wherein the sequence of the peptide fragment comprises a peptide sequence listed in Table 11.10. The method of embodiment 8, wherein the citrullination site selected from one or more citrullination sites shown in Table 11 or 12, or wherein the sequence of the peptide fragment comprises one of the following sequences, wherein the citrullination site is designated by underlining: AITTRSGQTLSK (SEQ ID NO: 247), ESSSHHPGIAEFPSRGK (SEQ ID NO: 248), QFTSSTSYNRGDSTFESK (SEQ ID NO: 249), SGQSEDRQPVPGQQMTLK (SEQ ID NO: 250), QLGLPGPPDVPDHAAYHPFRR (SEQ ID NO: 252), and GPCRAFIQLWAFDAVK (SEQ ID NO: 253).11. The method of any one of embodiments 1 to 7, wherein the biological sample comprises blood or is derived from blood.12. The method of any one of embodiments 1 to 7, wherein the biological sample comprises serum.13. the method of any one of embodiments 1 to 7, wherein the biological sample comprises plasma.14. The method of any one of embodiments 1 to 11, wherein the biological sample comprises blood supernatant.15. The method of any one of embodiments 1 to 6 or 8 to 14, wherein the biological sample has been exposed to the PALM modulator by contacting the biological sample with the PALM modulator ex vivo.16. The method of any one of embodiments 1 to 15, wherein the method comprises freezing and thawing the biological sample before assessing citrullination of the citrullination site.17. The method of any one of embodiments 1 to 16, wherein assessing citrullination of the citrullination site comprises mass spectrometry (MS).18. The method of any one of embodiments 1 to 16, wherein assessing citrullination of the citrullination site comprises liquid chromatography and mass spectrometry (LC-MS).19. The method of any one of embodiments 1-18, comprising preparing the biological sample for assessment prior to the assessing.20. The method of embodiment 19, wherein the preparing comprises enzymatically digesting proteins in the biological sample.21. The method of embodiment 19 or 20, wherein the preparing comprises depleting proteins from the biological sample that are not targeted by the assessing.22. The method of any one of embodiments 19 to 21, wherein the preparing comprises diluting the biological sample.23. The method of any one of embodiments 19 to 22, wherein the preparing comprises denaturing proteins in the biological sample.24. The method of any one of embodiments 19 to 23, wherein the preparing comprises enriching the biological sample for a protein or peptide fragment thereof that comprises the citrullination site to be assessed.25. The method of embodiment 24, wherein the preparing comprises contacting the biological sample with an antibody that specifically binds to citrullinated and noncitrullinated forms of the protein or peptide that comprises the citrullination site to be assessed.26. The method of any one of embodiments 1 to 25, wherein the method comprises contacting the biological sample with exogenous PALM.27. The method of embodiment 26, wherein the method comprises incubating the exogenous PALM with the biological sample.28. The method of embodiment 27, wherein the method comprises incubating the exogenous PAD4 with the biological sample at a temperature of 36-38 °C.29. The method of embodiment 27 or 28, wherein the incubating is for 1-3 hours.30. The method of any one of embodiments 27 to 29, wherein the method comprises adding EDTA to the biological sample after the incubation with exogenous PALM.31. The method of any one of embodiments 1 to 30, wherein the method comprises incubating the biological sample for an incubation period before assessing citrullination.32. The method of embodiment 31, wherein the incubating is performed at 35-40°C.33. The method of embodiment 31 or 32, wherein the incubation period is 48 to 96 hours.34. The method of any one of embodiments 1 to 33, wherein assessing citrullination of the citrullination site comprises measuring, in the biological sample, a first concentration of citrullinated protein or peptide and a second concentration of corresponding total protein.35. The method of embodiment 34, wherein assessing citrullination of the citrullination site comprises determining a citrullination ratio, wherein the citrullination ratio is a ratio of the first concentration to the second concentration.36. The method of embodiment 35, wherein the method comprises comparing the citrullination ratio to a reference citrullination ratio.37. The method of embodiment 36, wherein the reference citrullination ratio is a citrullination ratio determined for a control biological sample.38. The method of embodiment 37, wherein the control biological sample is a biological sample that has not been exposed to the PALM modulator.39. The method of any one of embodiments 36-38, wherein the assessing comprises determining a difference between the citrullination ratio for the biological sample and the reference citrullination ratio.40. A method of assessing the activity of a PALM modulator, the method comprising(a) obtaining a biological sample from a subject following treatment of the subject with at least one dose of a PALM modulator, and(b) assessing citrullination of a citrullination site on a protein or a peptide fragment thereof that is present in the biological sample.41. An in vitro method of assessing the activity of a PALM modulator, the method comprising(a) treating a biological sample from a subject with a PALM modulator to form a treated biological sample, and after the treating,(b) assessing citrullination of a citrullination site on a protein or a peptide fragment thereof that is present in the biological sample.42. The method of embodiment 40 or 41, further comprising assessing citrullination of the citrullination site on the protein or peptide fragment in a control biological sample.43. The method of embodiment 42, further comprising comparing an outcome of the assessment of citrullination in the biological sample with a corresponding outcome of the assessment of citrullination in the control biological sample.44. The method of any one of embodiments 40-43, wherein the assessing comprises (i) measuring a first concentration of citrullinated protein or peptide in the sample and (ii) measuring a second concentration of corresponding total protein in the sample, wherein the citrullinated protein or peptide is citrullinated at the citrullination site and the corresponding total protein encompasses modified and unmodified forms of the protein, and optionally (iii) determining a citrullination ratio, which is a ratio of the first concentration to the second concentration.45. The method of embodiment 44, wherein the method comprises comparing the citrullination ratio of the biological sample to the citrullination ratio of a control biological sample.46. The method of any one of embodiments 42-43 or 45, wherein the control biological sample is from the same subject as the biological sample.47. The method of embodiment 46, wherein the control biological sample is a biological sample obtained from the subject prior to treatment with a PALM modulator.48. The method of any one of embodiments 42-43 or 45-46, wherein the control biological sample has not been exposed to the PALM modulator.49. The method of any one of embodiments 42-43 or 45-46, wherein the control biological sample has been exposed to a different treatment than the biological sample.50. The method of any one of embodiments 40-49, wherein the PALM modulator is a PALM inhibitor.51. The method of any one of embodiments 40 or 42-50, further comprising selecting or adjusting a dose of the PALM modulator based on the outcome of the assessing.52. An in vitro method of assessing the activity of a PALM modulator, the method comprising(i) dividing a biological sample obtained from a subject into a plurality of biological samples,(ii) contacting each of the plurality of biological samples with a different dose of the PALMmodulator, and(iii) assessing, for each of the plurality of biological samples, citrullination of a PAD4- dependent citrullination site on a protein or peptide fragment thereof that is present in the biological sample.53. The method of embodiment 52, wherein the PAD4 modulator is a PAD4 inhibitor.54. The method of embodiment 52 or 53, further comprising calculating an IC50 for the PALM modulator based on the outcome of the assessing.55. The method of any one of embodiments 52-54, further comprising selecting or adjusting a dose of a PALM modulator to be administered to the subject based on the outcome of the assessing.56. An in vitro method of assessing citrullination by endogenous PALM, the method comprising(a) incubating a whole blood sample from a subject at 35-40°C for an incubation period,(b) after the incubation period, separating plasma or supernatant from the whole blood sample, and(c) assessing citrullination of a citrullination site on a protein or peptide fragment thereof that is present in the plasma or supernatant.57. The method of embodiment 56, wherein the incubation period is 48 to 96 hours.58. The method of any one of embodiments 56 or 57, wherein the incubating is at a temperature of 36 to 39°C, at a temperature of 36 to 38°C, or at a temperature of 37°C.59. The method of any one of embodiments 56-58, comprising enzymatically digesting polypeptides in the plasma or supernatant before the assessing.60. The method of any one of embodiments 56-59, further comprising (i) incubating the plasma or supernatant with a protein depletion resin, and (ii) recovering depleted plasma or supernatant that has flowed through the resin to obtain depleted flowthrough, optionally wherein the recovering comprises centrifugation.61. The method of embodiment 60, comprising enzymatically digesting polypeptides in the depleted flowthrough before the assessing.62. The method of embodiment 60 or 61, further comprising cleaning up enzymatically digested plasma or supernatant before the assessing.63. The method of any one of embodiments 56-62, wherein the whole blood sample and the plasma or supernatant separated therefrom have not been frozen and thawed.64. The method of any one of embodiments 56-62, wherein the whole blood sample and / or the plasma or supernatant separated therefrom has been frozen and thawed.65. The method of embodiment 64, wherein the method comprises freezing the plasma or supernatant after the separating and subsequently thawing the plasma or supernatant before the assessing.66. The method of any one of embodiments 56-65, wherein the whole blood sample has been exposed to a PALM modulator.67. The method of embodiment 66, wherein the whole blood sample has been exposed to a PALM modulator in vitro.68. The method of embodiment 66, wherein the whole blood sample has been exposed to a PALM modulator in vivo in the subject as a result of the PALM modulator being administered to the subj ect.69. An in vitro method of assessing changes in citrullination in a subject, the method comprising(a) incubating a whole blood sample from a subject at 35-40°C for an incubation period, wherein the sample is obtained from the subject following administration of a PALM modulator to the subject,(b) after the incubation period, separating plasma or supernatant from the whole blood sample, and(c) assessing citrullination of a citrullination site on a protein or peptide fragment thereof that is present in the plasma or supernatant.70. The method of embodiment 69, further comprising(d) incubating a second whole blood sample from the subject at 35-40°C for an incubation period, wherein the second whole blood sample is obtained from the subject before administration of the PALM modulator to the subject,(e) after the incubation period, separating plasma or supernatant from the second whole blood sample, and(f) assessing citrullination of a citrullination site on a protein or peptide fragment thereof that is present in the plasma or supernatant from the second whole blood sample.71. The method of embodiment 70, further comprising comparing an outcome of the assessing in step (f) with an outcome of the assessing in step (c).72. A method of assessing effects of a PALM modulator, the method comprising(a) exposing a whole blood sample from a subject to a PALM modulator in vitro,(b) incubating the whole blood sample at 35-40°C for an incubation period,(c) after the incubation period, separating plasma or supernatant from the whole blood sample, and(d) assessing citrullination of a citrullination site on a protein or peptide fragment thereof that is present in the plasma or supernatant.73. The method of embodiment 72, further comprising(e) incubating a control whole blood sample at 35-40°C for an incubation period,(f) after the incubation period, separating control plasma or supernatant from the control whole blood sample, and(g) assessing citrullination of a citrullination site on a protein or peptide fragment thereof that is present in the control plasma or supernatant.74. The method of embodiment 73, further comprising comparing an outcome of the assessing in step (g) with an outcome of the assessing in step (d).75. An in vitro method of assessing PAD4-dependent citrullination, the method comprising assessing citrullination of a citrullination site on a protein or peptide fragment thereof that is present in plasma or supernatant that has been separated from a whole blood sample that has been incubated at 35-40°C for an incubation period.76. The method of embodiment 75, wherein the plasma or supernatant has been frozen and the method comprises thawing the plasma or supernatant prior to the assessing.77. A method comprising:(a) immunoenriching a sample for a protein of interest to form an immunoenriched sample, wherein the immunoenriching comprises contacting the sample with an antibody that specifically binds to both citrullinated and noncitrullinated forms of the protein of interest, the protein of interest comprising a citrullination site, and(b) assessing citrullination in the immunoenriched sample at the citrullination site, optionally wherein the sample is a serum or plasma sample.78. A method comprising:(a) immunoenriching a sample for a protein or a peptide of interest to form an immunoenriched sample, wherein the immunoenriching comprises contacting the sample with an antibody that binds to both citrullinated and noncitrullinated forms of the protein or peptide of interest, the protein or peptide of interest comprising a citrullination site,(b) enzymatically digesting the immunoenriched sample to form digested peptides from the protein of interest either before or after the immunoenriching, and(c) assessing citrullination of the digested peptides at the citrullination site, optionally wherein the sample is a serum or plasma sample.79. A method comprising(a) immunoenriching a sample by contacting the sample with an immobilized antibody that binds to both citrullinated and noncitrullinated forms of a protein of interest, the protein of interest comprising a citrullination site,(b) eluting protein bound to the immobilized antibody,(d) enzymatically digesting the eluted protein to form digested peptides, and(e) assessing citrullination of the digested peptides at the citrullination site, optionally wherein the sample is a serum or plasma sample.80. The method of embodiment 77, 78, or 79, wherein the immunoenriching comprises incubating the sample with the immobilized antibody for at least 30 minutes.81. The method of embodiment 80, wherein the incubating is at a temperature of 22-28°C.82. The method of embodiment 80-81, wherein the incubating is for a period of 30 to 90 minutes.83. The method of any one of embodiments 77-82, wherein the immunoenriching comprises shaking during the incubating.84. The method of any one of embodiments 77-83, wherein the immunoenriching comprises removing the immobilized antibody from the sample and washing the immobilized antibody prior to the eluting.85. The method of any one of embodiments 79-84, wherein the eluting comprises washing the immobilized antibody with an elution composition under acidic conditions.86. The method of embodiment 85, wherein the elution composition comprises a detergent.87. The method of embodiment 86, wherein the detergent is a zwitterionic detergent.88. The method of any one of embodiments 85-87, the method comprises neutralizing eluted protein in a buffer prior to assessing, and optionally prior to enzymatically digesting.89. The method of any one of embodiments 77-88, wherein the antibody is immobilized by attachment to a solid surface.90. The method of any one of embodiments 77-89, wherein the assessing citrullination comprises measuring a first concentration of citrullinated peptide in the digested peptides and a second concentration of signature peptide in the digested peptides, and optionallydetermining a citrullination ratio, wherein the citrullination ratio is a ratio of the first concentration to the second concentration.91. The method of any one of embodiments 77-90, comprising denaturing proteins in the immunoenriched sample prior to the assessing.92. The method of any one of embodiments 79-90, comprising denaturing the eluted protein prior to the assessing.93. The method of embodiment 92, comprising denaturing the eluted protein prior to enzymatically digesting the eluted protein.94. The method of any one of embodiments 77-93, comprising diluting the sample prior to the immunoenriching and performing the immunoenriching on the sample that has been diluted.95. The method of embodiment 94, comprising diluting the sample by 2 to 1000 fold.96. The method of embodiment 94 or 95, wherein the sample that has been diluted has a volume of at least 5 pl.97. The method of any one of embodiments 40 to 96, wherein the assessing comprises mass spectrometry (MS).98. The method of embodiment 97, wherein the assessing comprises liquid chromatography and mass spectrometry (LC-MS).99. The method of embodiment 98, wherein the assessing comprises selective reaction monitoring and chromatographic separation.100. The method of any one of embodiments 77-99, wherein the method comprises assessing citrullination of two or more proteins of interest and the antibody comprises antibodies that specifically bind citrullinated and noncitrullinated forms of each of the two or more proteins of interest.101. A method comprising(i) contacting a biological sample from a subject with exogenous PALM and(ii) assessing citrullination of a citrullination site on a protein or a peptide fragment thereof that is present in a biological sample.102. The method of embodiment 101, wherein the biological sample comprises plasma or serum.103. The method of embodiment 101 or 102, wherein the method comprises preparing the biological sample for assessment prior to the assessing.104. The method of embodiment 103, wherein the preparing comprises enzymatically digesting proteins in the biological sample to produce digested peptides and optionally cleaning up the digested peptides.105. The method of embodiment 103 or 104, wherein the preparing comprises depleting proteins from the biological sample that are not targeted by the assessing.106. The method of any one of embodiment 105, wherein depleting comprises depletion of human serum albumin.107. The method of any one of embodiments 101-106, wherein the preparing comprises immunoenriching the biological sample for the protein or peptide fragment thereof using an antibody that binds to citrullinated and non-citrullinated forms of the protein or peptide.108. The method of any one of embodiments 40 to 107, wherein the protein or peptide fragment thereof or the protein of interest is selected from one or more of: alpha-2-HS- glycoprotein, alpha-2-macroglobulin, albumin, antithrombin-III, apolipoprotein A-I, apolipoprotein A-IV, apolipoprotein B-100, apolipoprotein E, apolipoprotein LI, C4b- binding protein alpha chain, ceruloplasmin, clusterin, complement C2, complement C3, complement C4-A, complement C4-B, complement factor B, complement factor H, complement factor I, complement component C9, fibrinogen alpha chain, fibrinogen beta chain, fibrinogen gamma chain, fibronectin, galectin-3 -binding protein, gelsolin, haptoglobin, haptoglobin-related protein, hemopexin, immunoglobulin heavy variable 1-3, immunoglobulin heavy variable 1-8, immunoglobulin heavy variable 1-46, immunoglobulin heavy variable 1-69, immunoglobulin heavy variable 1-69D, inter-alpha-trypsin inhibitor heavy chain H4, immunoglobulin lambda-like polypeptide 1, immunoglobulin heavy constant mu, inter-alpha-trypsin inhibitor heavy chain H2, isoform 2 of complement C4-A, plasminogen, plasminogen-like protein A, alpha- 1-microglobulin / bikunin precursor (protein AMBP), prothrombin, proteoglycan 4, serotransferrin, serum amyloid A-l protein, serum amyloid A-2 protein, serum amyloid A-4 protein, stromelysin- 1, vitamin D-binding protein, and vitronectin.109. The method of any one of embodiments 40-107, wherein the citrullination site is selected from one or more citrullination sites shown in Table A or in one or more of Tables 3- 18.111. The method of any one of embodiments 40-107, wherein the citrullination site is selected from one or more of the following:R1391 of proteoglycan 4 (corresponding to R1391 of Q92954), R573 of fibrinogen alpha chain (corresponding to R573 of P02671), R591 of fibrinogen alpha chain (corresponding to R591 of P02671), R573 of complement C3 (corresponding to R573 of PO 1024), R748 of complement C3 (corresponding to R573 of PO 1024),R688 of inter-alpha-trypsin inhibitor heavy chain H4 (corresponding to R688 of QI 4624),R297 of protein AMBP (corresponding to R297 of P02760), R715 of alpha-2-macroglobulin (corresponding to R715 of PO 1023), R32 of gel solin (corresponding to R32 of P06396), R59 of haptoglobin (corresponding to R59 of P00738), and R651 of serotransferrin (corresponding to R651 ofP02787).112. The method of any one of embodiments 40-107, the method comprising assessing citrullination of a peptide fragment, wherein the sequence of the peptide fragment comprises one of the following sequences, wherein the citrullination site is designated by underlining: AITTRSGQTLSK (SEQ ID NO: 247), ESSSHHPGIAEFPSRGK (SEQ ID NO: 248), QFTSSTSYNRGDSTFESK (SEQ ID NO: 249), SGQSEDRQPVPGQQMTLK (SEQ ID NO: 250), ASHLGLARSNLDEDIIAEENIVSR (SEQ ID NO: 251), QLGLPGPPDVPDHAAYHPFRR (SEQ ID NO: 252), GPCRAFIQLWAFDAVK (SEQ ID NO: 253), VGFYESDVMGRGHAR (SEQ ID NO: 254), ATASRGASQAGAPQGR (SEQ ID NO: 255), LRTEGDGVYTLNDK (SEQ ID NO: 256), and DLLFRDDTVCLAK (SEQ ID NO: 257).113. The method of any one of embodiments 40-107, wherein the protein or peptide fragment thereof or the protein of interest comprises fibrinogen alpha chain or a peptide fragment thereof and / or gelsolin or a peptide fragment thereof.114. The method of embodiment 113, wherein the protein or peptide fragment thereof or the protein of interest is fibrinogen alpha chain or a peptide fragment thereof.115. The method of embodiment 114, wherein the citrullination site is at R591 of P02671 or R593 ofP02671.116. The method of embodiment 114 or 115, wherein the method comprises (a) assessing citrullination of a peptide comprising the amino acid sequence of QFTSSTSYNRGDSTFESK (SEQ ID NO: 249), wherein the underlined R is thecitrullination site or (b) assessing citrullination of a peptide comprising the amino acid sequence of ESSSHHPGIAEFPSRGK (SEQ ID NO: 248), wherein the underlined R is the citrullination site.117. The method of any one of embodiments 40-107, wherein the protein or peptide fragment thereof or the protein of interest comprises gelsolin or a peptide fragment thereof.118. The method of embodiment 117, wherein the citrullination site is at R32 of P06396.119. The method of embodiment 117 or 118, wherein the method comprises assessing citrullination of a peptide comprising the amino acid sequence of ATASRGASQAGAPQGR (SEQ ID NO: 255), wherein the underlined R is the citrullination site.120. A method of assessing citrullination at a citrullination site, the method comprising(i) measuring a first concentration of a citrullinated protein or a citrullinated peptide in a biological sample by mass spectrometry (MS), wherein the citrullinated protein or citrullinated peptide is citrullinated at a citrullination site, and(ii) measuring a second concentration of corresponding total protein in the biological sample by MS.121. The method of embodiment 120, wherein the method comprises (i) measuring a first concentration of a citrullinated peptide from a target protein in a biological sample by MS, wherein the citrullinated peptide is citrullinated at a citrullination site, and (ii) measuring the second concentration by measuring the concentration of a signature peptide from the target protein in the biological sample by MS.122. The method of embodiment 120 or 121, further comprising calculating a ratio of the first concentration to the second concentration123. The method of any one of embodiments 120 to 122, wherein the method comprises measuring the first concentration and the second concentration for each of a plurality of different proteins or peptides.124. The method of embodiment 123, wherein the method comprises measuring the first concentration for each of two different peptides, each of which are nonoverlapping fragments of the same protein and contain different citrullination sites.125. The method of embodiment 123 or 124, wherein the method comprises calculating a ratio of the first concentration to the second concentration for each of the plurality of different proteins or peptides.126. The method of any one of embodiments 120 to 125, wherein the citrullination site is a site listed in Table A or in one or more of Tables 3-18.127. The method of any one of embodiments 120 to 126, wherein (i) the citrullinated protein is selected from alpha-2-HS-glycoprotein, alpha-2-macroglobulin, albumin, antithrombin-III, apolipoprotein A-I, apolipoprotein A-IV, apolipoprotein B-100, apolipoprotein E, apolipoprotein LI, C4b-binding protein alpha chain, ceruloplasmin, clusterin, complement C2, complement C3, complement C4-A, complement C4-B, complement factor B, complement factor H, complement factor I, complement component C9, fibrinogen alpha chain, fibrinogen beta chain, fibrinogen gamma chain, fibronectin, galectin-3 -binding protein, gelsolin, haptoglobin, haptoglobin-related protein, hemopexin, immunoglobulin heavy variable 1-3, immunoglobulin heavy variable 1-8, immunoglobulin heavy variable 1-46, immunoglobulin heavy variable 1-69, immunoglobulin heavy variable 1-69D, inter-alphatrypsin inhibitor heavy chain H4, immunoglobulin lambda-like polypeptide 1, immunoglobulin heavy constant mu, inter-alpha-trypsin inhibitor heavy chain H2, isoform 2 of complement C4-A, plasminogen, plasminogen-like protein A, alpha- 1- microglobulin / bikunin precursor, prothrombin, proteoglycan 4, serotransferrin, serum amyloid A-l protein, serum amyloid A-2 protein, serum amyloid A-4 protein, stromelysin- 1, vitamin D-binding protein, and vitronectin; or (ii) the citrullinated peptide is a peptide fragment of a protein listed in (i).128. The method of any one of embodiments 120 to 127, wherein the citrullinated peptide comprises a sequence selected from the peptide sequences listed in Tables 3-18.129. The method of any one of embodiments 120 to 128, wherein (i) the citrullinated protein is selected from proteoglycan 4, fibrinogen alpha chain, complement C3, inter-alpha-trypsin inhibitor heavy chain H4, protein AMBP, alpha-2 macroglobulin, gelsolin, haptoglobin, and serotransferrin, or (ii) the citrullinated peptide is a peptide fragment of a protein listed in (i).130. The method of any one of embodiments 120 to 129, wherein the citrullination site is selected fromR1391 of proteoglycan 4 (corresponding to R1391 of Q92954), R573 of fibrinogen alpha chain (corresponding to R573 of P02671), R591 of fibrinogen alpha chain (corresponding to R591 of P02671), R573 of complement C3 (corresponding to R573 of P01024), R748 of complement C3 (corresponding to R573 of P01024), R688 of inter-alpha-trypsin inhibitor heavy chain H4 (corresponding to R688 of QI 4624),R297 of protein AMBP (corresponding to R297 of P02760),R715 of alpha-2-macroglobulin (corresponding to R715 of PO 1023),R32 of gel solin (corresponding to R32 of P06396),R59 of haptoglobin (corresponding to R59 of P00738), and R651 of serotransferrin (corresponding to R651 ofP02787).131. The method of any one of embodiments 120 to 130, wherein the method comprises measuring the amount of a citrullinated peptide comprising a peptide sequence selected from: AITTRSGQTLSK (SEQ ID NO: 247), ESSSHHPGIAEFPSRGK (SEQ ID NO: 248), QFTSSTSYNRGDSTFESK (SEQ ID NO: 249), SGQSEDRQPVPGQQMTLK (SEQ ID NO: 250), ASHLGLARSNLDEDIIAEENIVSR (SEQ ID NO: 251), QLGLPGPPDVPDHAAYHPFRR (SEQ ID NO: 252), GPCRAFIQLWAFDAVK (SEQ ID NO: 253), VGFYESDVMGRGHAR (SEQ ID NO: 254), ATASRGASQAGAPQGR (SEQ ID NO: 255), LRTEGDGVYTLNDK (SEQ ID NO: 256), and DLLFRDDTVCLAK (SEQ ID NO: 257), in each case wherein the underlined R is the citrullination site.132. The method of any one of embodiments 120-131, wherein the citrullinated protein or citrullinated peptide comprises fibrinogen alpha chain and / or gelsolin or a peptide fragment thereof.133. The method of embodiment 132, wherein the citrullinated protein or citrullinated peptide is fibrinogen alpha chain or a peptide fragment thereof.134. The method of embodiment 133, wherein the citrullination site is at R591 of P02671 or R593 ofP02671.135. The method of embodiment 133 or 134, wherein the citrullinated peptide comprises the amino acid sequence of QFTSSTSYNRGDSTFESK (SEQ ID NO: 249), wherein the underlined R is the citrullination site, or wherein the citrullinated peptide comprises the amino acid sequence of ESSSHHPGIAEFPSRGK (SEQ ID NO: 248), wherein the underlined R is the citrullination site.136. The method of embodiment 132, wherein the citrullinated protein or citrullinated peptide comprises gelsolin or a peptide fragment thereof.137. The method of embodiment 136, wherein the citrullination site is at R32 of P06396.138. The method of embodiment 136 or 137, wherein the citrullinated peptide comprises the amino acid sequence of ATASRGASQAGAPQGR (SEQ ID NO: 255), wherein the underlined R is the citrullination site.139. The method of any one of embodiments 120-138, wherein the biological sample is obtained from a subject.140. The method of embodiment 139, wherein the biological sample is a whole blood, plasma, serum, blood supernatant, or synovial fluid sample.141. The method of embodiment 139 or 140, wherein the method further comprises comparing the first and second concentrations to first and second concentrations obtained from a control biological sample.142. The method of embodiment 139, 140 or 141, wherein the method further comprises determining one or more of the following based on the first and second concentrations or a ratio of the first and second concentrations: probability of a clinical outcome, risk for developing a citrullination-related disease, and diagnosis of a citrullination-related disease.143. The method of embodiment 142, wherein the method further comprises selecting the subject from which the biological sample was derived for treatment of a citrullination-related disease.144. The method of embodiment 143, wherein the PALM modulator is a PALM inhibitor.145. The method of any one of embodiments 1-144, wherein the biological sample is obtained from a subject that is ACPA positive.146. The method of any one of embodiments 1-145, wherein the biological sample is obtained from a subject that is positive for endogenous PALM antibodies.147. The method of embodiment 146, wherein the subject is positive for endogenous PALM activating antibodies.148. The method of any one of embodiments 1-147, wherein the biological sample is obtained from a subject that has been diagnosed with a citrullination-related disease or is at risk for developing a citrullination-related disease.149. The method of embodiment 148, wherein the citrullination-related disease is an autoimmune disorder.150. The method of embodiment 148, wherein the citrullination-related disease is rheumatoid arthritis, lupus (e.g., systemic lupus erythematosus (SLE)), lupus nephritis, vasculitis (e.g., ANCA-associated vasculitis), thrombosis (e.g, venous thrombosis), or inflammatory bowel disease (IBD) (e.g., ulcerative colitis, Crohn’s disease).151. The method of any one of embodiments 1-144, wherein the biological sample is obtained from a subject that is a normal, healthy subject.Any of the method embodiments listed above that include a PAD4 modulator may, in further embodiments, also be performed with other therapeutic agents. Nonlimiting examples of such other therapeutic agents include agents that may be used for treatment of citrullination-related diseases, and agents that target molecules involved in biological pathways, such as, for example, NETosis or METosis, which may also involve PAD4. Thus, in the above such methods, a PAD4 modulator may be substituted with such another therapeutic agent. In any of the above embodiments, where a PAD4 modulator is included in the method, the PAD4 modulator may, in some cases, be a PAD4 inhibitor, examples of which are provided throughout the disclosure.In any of the above embodiments, in some cases the assessing of citrullination may be performed by MS, including by LC-MS, for example. In any of the above embodiments, unless particular citrullination sites or proteins or peptides are recited, citrullination sites for assessment may be as recited, for instance, in embodiments above. In any of the methods herein, unless stated otherwise above, biological samples may be any such samples recited herein, including without limitation, biological fluid samples such as blood, plasma, serum, blood supernatant, synovial fluid, lymph, pleural fluid, interstitial fluid, sweat, tears, sputum, or urine, as well as tissue samples. As also indicated above, in any of the methods herein, a citrullination ratio, as described below, and / or a concentration of citrullinated protein or peptide and a concentration of corresponding total protein may be determined as part of the method. In addition, in any of the methods, as indicated above, a biological sample may be prepared prior to assessing, in a variety of ways, such as dilution, freezing and thawing, denaturing of proteins, enzymatic digestion of proteins, separation of a supernatant from the sample for analysis, and the like. The above embodiments may also be applied to control samples as well as to biological samples of interest, for instance, to allow for comparisons of citrullination assessments between samples of interest and controls.It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the claims. References cited herein are incorporated by reference in their entirety, and the amino acid sequences of proteins obtainable at www.uniprot.org through their UniProt accession numbers provided herein are also incorporated herein by reference.BRIEF DESCRIPTION OF THE DRAWINGSFIG. 1 shows dose-dependent inhibition of human PAD4 with antibody hzl3-5 D31E at four concentrations of recombinant human PAD4 (rhPAD4) ranging from 13.5 nM (1 pg / mL) to 108 nM (8 pg / mL).FIGs. 2A-2F show reduced extracellular citrullinated histone 3 in lipopolysaccharide (LPS)-stimulated human CD14+ monocytes treated with the specified concentrations of an indicated antibody or with isotype control antibody. FIG. 2A shows citrullinated histone 3 levels in monocytes incubated with hzl3-5. FIG. 2B shows citrullinated histone 3 levels in monocytes incubated with hzl3-5 D31E. FIG. 2C citrullinated histone 3 levels in monocytes incubated with hz20-2. FIG. 2D shows citrullinated histone 3 levels in monocytes incubated with hz20-7. FIG. 2E shows citrullinated histone 3 levels in monocytes incubated with hzl3- 3. FIG. 2F shows citrullinated histone 3 levels in monocytes incubated with hzl3-12.FIGs. 3 A-3E show efficacy of anti-human PAD4 mAbs and humanized derivatives in an LPS ALI PD model. FIG. 3 A, FIG. 3B, and FIG. 3C respectively show the effects of clone 20, humanized clone 20-based hz20-2 antibody and humanized clone 20-based hz20-7 antibody at the indicated doses on extracellular citrullinated H3 relative to total extracellular H3; the percent reductions indicate reductions relative to the isotype control condition. FIG. 3D and FIG. 3E respectively show the effects of clone 20-based hz20-2 antibody and clone 20-based hz20-7 antibody at the indicated doses on extracellular citrullinated ITIH4 relative to total extracellular ITIH4; the percent reductions indicate reductions relative to the isotype control condition. “Mpk” = mg / kg. “IC” = Isotype Control antibody. “Naive”= not nebulized with LPS.FIGs. 4A-4E show efficacy of anti-human PAD4 mAbs clone 13 and humanized derivatives in an LPS ALI PD model. FIG. 4 A, FIG. 4B, and FIG. 4C respectively show the effects of clone 13, humanized clone 13 -based hz 13-12 antibody, and humanized clone 13- based hzl3-5 antibody at the indicated doses on extracellular citrullinated H3 relative to total extracellular H3; the percent reductions indicate reductions relative to the isotype control condition. FIG. 4D and FIG. 4E respectively show the effects of clone 13 -based hzl3-12 antibody and clone 13 -based hzl3-5 antibody at the indicated doses on extracellular citrullinated ITIH4 relative to total extracellular ITIH4; the percent reductions indicate reductions relative to the isotype control condition. “Mpk” = mg / kg. “IC” = Isotype Control antibody. “Naive”= not nebulized with LPS.FIGs. 5A-5E show experimental design and human PAD4 endpoints of an LPS AJI PD study using Hu-PAD4 knock-in mice. FIG. 5A shows a study timetable. FIG. 5B shows an overview of experimental procedures including treatment at the knee joint and extraction of citrullinated proteins from explanted tissue. Extracellular Cit-PRG4 (FIG. 5C), extracellular Cit-ITIH4 (FIG. 5D) and human PAD4 (FIG. 5E) of patella explant supernatant are shown.FIGs. 6A-6C show efficacy of anti-human PAD4 antibodies in an LPS AJI PD study. The effects of clone 13 -based hzl3-12 antibody (FIG. 6 A), clone 13 -based hzl3-5 antibody (FIG. 6B), and clone 20-based hz20-2 antibody (FIG. 6C) at the indicated doses on extracellular citrullinated ITIH4 relative to total extracellular ITIH4 are shown; the percent reductions indicate reductions relative to the isotype control condition. “Mpk” = mg / kg. “IC” = Isotype Control antibody. “Naive”= not injected with pristane. “PBS” = naive, injected with phosphate buffered saline in place of LPS.FIGs. 7A-7C show efficacy of anti-human PAD4 antibodies in an LPS AJI PD study. Extracellular Cit-PRG4 of patella explant supernatant is shown. The effects of clone 13-based hzl3-12 antibody (FIG. 7 A), clone 13 -based hzl3-5 antibody (FIG. 7B), and clone 20-based hz20-2 antibody (FIG. 7C) at the indicated doses on extracellular citrullinated PRG4 relative to total extracellular PRG4 are shown; the percent reductions indicate reductions relative to the isotype control condition. “Mpk” = mg / kg. “IC” = Isotype Control antibody. “PBS”= phosphate buffered saline. “Naive”= not injected with LPS.FIGs. 8A-8B show efficacy of anti-human PAD4 antibodies hzl3-5 and hzl3-5 D31E in an LPS AJI study. The antibodies inhibited citrullination of ITIH4 (FIG. 8 A) and PRG4 (FIG. 8B); results showed dose dependent inhibition by the hzl3-5 D31E antibody. “Mpk” = mg / kg. “IC” = Isotype Control antibody. “Naive”= not injected with LPS.FIG. 9A-9D show induction of citrullination and inhibition of citrullination ex vivo in incubated blood. Whole blood samples were treated with Ab hzl3-5 D3 IE, PBS (control), or isotype control and incubated for 48 h at 37°C for induction of citrullination. PBS-Oh shows citrullination levels before induction. Samples were analyzed using global proteomics. Citrullination of the peptides listed in Table 10 was assessed. The average % citrullination for each peptide, calculated as the average ratio of citrullinated peptide intensity to total protein intensity *100%, wherein the total protein intensity was measured by measuring the intensity of a signature peptide, is shown for 6 donors. Black bar: 1stblood draw; gray bar: repeat blood draw 1 week later. FIG. 9A shows the results for the gelsolin (GSN) peptide. Figurediscloses SEQ ID NO: 405. FIG. 9B shows the results for the complement C3 (C3) peptide. Figure discloses SEQ ID NO: 406. FIG. 9C shows the results for the SerpinCl peptide. Figure discloses SEQ ID NO: 407. FIG. 9D shows the results for the fibrinogen A (FGA) peptide. Figure discloses SEQ ID NO: 408.FIG. 10A-10C show that citrullination of endogenous serum proteins by exogenous PAD4 is inhibited by hzl3-5 D3 IE in a dose dependent manner. Samples were analyzed using targeted proteomic approach on nanoLC-TimsTOF platform. Citrullination of the peptides listed in Table 15 was assessed. The % citrullination is shown and was calculated as described for FIGs. 9A-9D. FIG. 10A shows inhibition of citrullination of the FGA peptide ESSSHHPGIAEFPSRGK (SEQ ID NO: 248). FIG. 10B shows inhibition of citrullination of the FGA peptide QFTSSTSYNRGDSTFESK (SEQ ID NO: 249). FIG. 10C shows inhibition of citrullination of the PRG4 peptide.FIG. 11 A-l IB show that induction and inhibition of citrullination ex vivo in incubated blood (from 1stdraw) was confirmed using a targeted proteomic approach. Whole blood samples were treated with Ab hzl3-5 D31E, PBS (control), or isotype control and incubated for 48 h at 37°C. PBS-Oh shows citrullination levels before induction. Samples were analyzed with targeted proteomics. Citrullination of GSN and FGA peptides, sequences of which are provided in Table 16, was assessed. The average % citrullination was calculated as described for FIGs. 9A-9D (N=6 donors). Error bars are standard errors of the mean. FIG. 11 A shows the results for the GSN peptide. FIG. 1 IB shows results for the FGA peptide.FIG. 12 shows targeted proteomic analysis of ex vivo citrullinated FGA in TruCulture samples after immunocapture enrichment. The FGA peptide QFTSSTSYNRGDSTFESK (SEQ ID NO: 249) was measured on the LC-TripleQuad 7500 system. Representative chromatograms are shown from two different donor samples in which citrullination percentages of 0.5% (left panel) and 2.6% (right panel) were measured. The % citrullination was calculated as described for FIGs. 9A-9D. Figure 12 also discloses “QFTSSTSYNRGDSTFES” as SEQ ID NO: 409.FIGs. 13 A-13B show that the hzl3-5 D3 IE antibody maintained potency in the presence of endogenous PAD4 antibodies from RA patients. FIG. 13 A shows PAD4 autoantibodies measured by OD450 in ELISA from purified IgG of serum samples of 21 RA patients and 10 healthy control subjects (NHV). FIG. 13B shows inhibition of H3 citrullination by hzl3-5 D3 IE in the presence of purified IgG from RA (closed squares) or NHV (open squares) serum. Dotted lines represent H3 citrullination by PAD4 in the presenceof purified IgG from RA donors (lower line) and NHV donors (upper line) without hzl3-5 D31E.FIG. 14 shows the citrullinated proteoglycan 4 (Cit-PRG4) plasma concentrations in pM from rheumatoid (RA) patents and normal healthy volunteers (NHV). Error bars represent mean ±SD. 30 RA and 30 NHV samples were analyzed for this dataset.DETAILED DESCRIPTION OF CERTAIN EMBODIMENTSI. DefinitionsUnless otherwise defined, scientific and technical terms used in connection with the present invention shall have the meanings that are commonly understood by those of ordinary skill in the art. Further, unless otherwise required by context, singular terms shall include pluralities and plural terms shall include the singular.In this application, the use of “or” means “and / or” unless stated otherwise. In the context of a multiple dependent claim, the use of “or” refers back to more than one preceding independent or dependent claim in the alternative only. Also, terms such as “element” or “component” encompass both elements and components comprising one unit and elements and components that comprise more than one subunit unless specifically stated otherwise.Exemplary techniques used in connection with recombinant DNA, oligonucleotide synthesis, tissue culture and transformation (e.g., electroporation, lipofection), enzymatic reactions, and purification techniques are described, e.g., in Sambrook et al. Molecular Cloning: A Laboratory Manual (2nd ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. (1989)), among other places.As used herein, the term “about” refers to a numeric value, including, for example, whole numbers, fractions, and percentages, whether or not explicitly indicated. The term “about” generally refers to a range of numerical values (e.g., + / -5-10% of the recited range) that one of ordinary skill in the art would consider equivalent to the recited value (e.g., having the same function or result). When terms such as at least and about precede a list of numerical values or ranges, the terms modify all of the values or ranges provided in the list. In some instances, the term about may include numerical values that are rounded to the nearest significant figure.The terms “subject” and “patient” are used interchangeably herein to refer to a human unless expressly indicated otherwise (i.e., a murine subject or the like).A “biological sample” herein refers to a sample taken from a biological source, such as from a subject. A “biological sample” may comprise fluid and / or tissue, and thus it may be a “biological fluid sample” or a “tissue sample,” and it may be processed, such as centrifuged or mixed with other agents or the like, in order to facilitate analysis. For example, certain biological fluid samples may comprise supernatant following separation of particulate and fluid matter. In some cases, the biological sample comprises, for example, blood or blood components such as whole blood, serum, plasma, or blood supernatant. In some cases, it may comprise synovial fluid. In other cases, the biological sample may be a tissue sample, for instance, a tumor sample or a neoplasia sample.The term “polypeptide” refers to a polymer of amino acid residues, and is not limited to a minimum length. A “protein” may comprise one or more polypeptides. Such polymers of amino acid residues may contain natural or non-natural amino acid residues, and include, but are not limited to, peptides, oligopeptides, dimers, trimers, and multimers of amino acid residues. Both full-length proteins and fragments thereof are encompassed by the definition. The terms also include post-expression modifications of the polypeptide, for example, glycosylation, sialylation, acetylation, phosphorylation, and the like. Furthermore, for purposes of the present invention, a “polypeptide” or “protein” refers to a polypeptide or protein, respectively, which includes modifications, such as deletions, additions, and substitutions (generally conservative in nature), to the native sequence, as long as the protein maintains the desired activity. These modifications may be deliberate, as through site- directed mutagenesis, or may be accidental, such as through mutations of hosts that produce the proteins or errors due to PCR amplification. A protein may comprise two or more polypeptides.The term “peptide fragment” or “peptide” of a longer polypeptide or protein (for example, a “protein or peptide fragment thereof’) refers to a portion of the polypeptide or protein. In some cases, analysis of a chemical modification of an amino acid residue in a polypeptide, for example, may be performed by analyzing a peptide fragment thereof that includes the amino acid residue in question.Some amino acids within a protein or its peptide fragment may be “citrullinated.” As used herein, this term means that the protein or its peptide fragment contains at least one amino acid that is converted from one of the 20 naturally occurring amino acids to a citrulline amino acid. For example, certain arginine (Arg, R) residues may be chemically modified to convert their side chains to the side chain of the amino acid citrulline (Cit). Thus, sucharginine residues, and the corresponding peptides or proteins on which they are found are referred to as being citrullinated.The amino acid residue that is converted to citrulline may also be referred to herein as a “citrullination site.” For example, a residue at a particular amino acid position within a protein may be citrullinated. In such a case, that particular amino acid position may be referred to as a “citrullination site.” A citrullination site herein may in some cases be identified with reference to an exemplary, reference amino acid sequence for the protein. In the case where a particular protein has more than one naturally occurring amino acid sequence, one such sequence may be provided herein as a reference sequence for identifying the residue corresponding to a citrullination site, and that site may be identified in other naturally occurring variants of the protein through sequence alignment with the reference sequence provided herein. A given protein may also have one or more such citrullination sites when more than one residue in the protein is found to be citrullinated.A “PAD” or “protein arginine deiminase” refers to an enzyme that catalyzes the conversion of arginine to citrulline in a protein or peptide under certain conditions. Examples of PADs include PAD4 and PAD2, for example.“PAD4” or “protein arginine deiminase 4” or “peptidyl arginine deiminase 4,” as used herein, refers to human PAD4 (huPAD4; UniProt ID: Q9UM07), unless expressly noted otherwise (i.e., murine PAD4, cynomolgus PAD4, or the like). Exemplary human PAD4 amino acid sequences are shown in SEQ ID NO: 1 and SEQ ID NO: 2 and SEQ ID NO: 3.As used herein, a “PAD4 modulator” refers to a compound (e.g, a small or large molecule or biologic) that alters (i.e., modulates) at least one activity or function of PAD4. In some cases, a “PAD4 modulator” is a “PAD4 inhibitor,” which is a compound that reduces at least one activity of PAD4, i.e., a PAD4 antagonist. In other cases, a “PAD4 modulator” is a compound that increases the activity of PAD4, i.e., a PAD4 agonist. The modulation of the activity of PAD4 may be by any mechanism and may be observed in vitro and / or in vivo. In some cases, a PAD4 modulator may modulate the activity of additional proteins in addition to PAD4, such as, for example, additional PAD enzymes, such as PAD2; while in other cases, the activity modulation may be specific to PAD4 and the PAD4 modulator does not modulate the activity of other proteins such as, for example, other PAD enzymes such as PAD2.The term “agonist” as used herein refers to a compound that causes an increase in at least one activity or function of a molecule to which it binds, or otherwise activates or helps to activate the molecule. The term “antagonist” or “inhibitor” as used herein refers to acompound that causes a decrease in at least one activity or function of a molecule to which it binds, or that otherwise blocks or inhibits at least one activity or function of the molecule.The terms “inhibition” or “inhibit” more generally refer to a decrease or cessation of any event (such as protein ligand binding) or to a decrease or cessation of any phenotypic characteristic or to the decrease or cessation in the incidence, degree, or likelihood of that characteristic. To “reduce” or “inhibit” is to decrease, reduce or arrest an activity, function, and / or amount as compared to a reference. It is not necessary that the inhibition or reduction be complete. For example, in certain embodiments, by “reduce” or “inhibit” is meant the ability to cause an overall decrease of 20% or greater. In another embodiment, by “reduce” or “inhibit” is meant the ability to cause an overall decrease of 50% or greater. In yet another embodiment, by “reduce” or “inhibit” is meant the ability to cause an overall decrease of 75%, 85%, 90%, 95%, or greater.In some cases, a PALM modulator may be a small molecule compound, or it may be a large molecule such as an antibody, or it may be another type of biologic. An “anti -PALM antibody” or a “PALM-antibody” or an “antibody that specifically binds to PALM” or an “antibody that binds to PALM” and similar phrases refer to an antibody that specifically binds to PALM as defined herein. The term “antibody” herein refers to a molecule comprising at least complementarity-determining region (CDR) 1, CDR2, and CDR3 of a heavy chain and at least CDR1, CDR2, and CDR3 of a light chain, wherein the molecule is capable of binding to antigen. The term is used in the broadest sense and encompasses various antibody structures, including but not limited to monoclonal antibodies, polyclonal antibodies, multispecific antibodies (e.g., bispecific antibodies, diabodies, etc.), full length antibodies, single-chain antibodies, antibody conjugates, and antibody fragments, so long as they exhibit the desired PALM-specific binding activity.An “isolated” antibody is one that has been separated from a component of its natural environment. In some aspects, an antibody is purified to greater than 95% or 99% purity as determined by, for example, electrophoretic (e.g., SDS-PAGE, isoelectric focusing (IEF), capillary electrophoresis) or chromatographic (e.g., ion exchange or reverse phase HPLC) methods. For a review of methods for assessment of antibody purity, see, e.g., Flatman et al., J. Chromatogr. B 848:79-87 (2007).An “antigen” refers to the target of an antibody, i.e., the molecule to which the antibody specifically binds. The term “epitope” denotes the site on an antigen, either proteinaceous or non-proteinaceous, to which an antibody binds. Epitopes on a protein can beformed both from contiguous amino acid stretches (linear epitope) or comprise noncontiguous amino acids (conformational epitope), e.g., coming in spatial proximity due to the folding of the antigen, i.e., by the tertiary folding of a proteinaceous antigen. Linear epitopes are typically still bound by an antibody after exposure of the proteinaceous antigen to denaturing agents, whereas conformational epitopes are typically destroyed upon treatment with denaturing agents.The term “heavy chain” refers to a polypeptide comprising at least a heavy chain variable region, with or without a leader sequence. In some embodiments, a heavy chain comprises at least a portion of a heavy chain constant region. The term “full-length heavy chain” refers to a polypeptide comprising a heavy chain variable region and a heavy chain constant region, with or without a leader sequence.The term “light chain” refers to a polypeptide comprising at least a light chain variable region, with or without a leader sequence. In some embodiments, a light chain comprises at least a portion of a light chain constant region. The term “full-length light chain” refers to a polypeptide comprising a light chain variable region and a light chain constant region, with or without a leader sequence.The term “complementarity determining regions” (“CDRs”) as used herein refers to each of the regions of an antibody variable region which are hypervariable in sequence and which determine antigen binding specificity. Generally, antibodies comprise six CDRs: three in the VH (CDR-H1 or heavy chain CDR1, CDR-H2, CDR-H3), and three in the VL (CDR- Ll, CDR-L2, CDR-L3). Unless otherwise indicated, the CDRs are determined according to the sequence table herein.“Framework” or “FR” refers to the residues of the variable region residues that are not part of the complementary determining regions (CDRs). The FR of a variable region generally consists of four FRs: FR1, FR2, FR3, and FR4. Accordingly, the CDR and FR sequences generally appear in the following sequence in VH (or VL): FR1-CDR-H1(CDR- L1)-FR2- CDR-H2(CDR-L2)-FR3- CDR-H3(CDR-L3)-FR4.The term “variable region” or “variable domain” refers to the domain of an antibody heavy or light chain that is involved in binding the antibody to antigen. The variable domains of the heavy chain and light chain (VH and VL, respectively) of a native antibody generally have similar structures, with each domain comprising four conserved framework regions (FRs) and three complementary determining regions (CDRs). See, e.g., Kindt et al. Kuby Immunology, 6thed., W.H. Freeman and Co., page 91 (2007). A variable domain maycomprise heavy chain (HC) CDR1-FR2-CDR2-FR3-CDR3 with or without all or a portion of FR1 and / or FR4; and light chain (LC) CDR1-FR2-CDR2-FR3-CDR3 with or without all or a portion of FR1 and / or FR4. That is, a variable domain may lack a portion of FR1 and / or FR4 so long as it retains antigen-binding activity. A single VH or VL domain may be sufficient to confer antigen-binding specificity. Furthermore, antibodies that bind a particular antigen may be isolated using a VH or VL domain from an antibody that binds the antigen to screen a library of complementary VL or VH domains, respectively. See, e.g., Portolano et al., J. Immunol. 150 :880-887 (1993) ; Clarkson et al., Nature 352 :624-628 (1991).The light chain and heavy chain “constant regions” of an antibody refer to additional sequence portions outside of the FRs and CDRs and variable regions. Certain antibody fragments may lack all or some of the constant regions. From N- to C-terminus, each heavy chain has a variable domain (VH), also called a variable heavy domain or a heavy chain variable region, followed by three constant heavy domains (CHI, CH2, and CH3). Similarly, from N- to C-terminus, each light chain has a variable domain (VL), also called a variable light domain or a light chain variable region, followed by a constant light (CL) domain.The term “Fc region” herein is used to define a C-terminal region of an immunoglobulin heavy chain that contains at least a portion of the constant region. The term includes native sequence Fc regions and variant Fc regions. In one aspect, a human IgG heavy chain Fc region extends from Cys226, or from Pro230, to the carboxyl-terminus of the heavy chain at Gly446 and Lys447 (EU numbering). Antibodies produced by host cells may undergo post-translational cleavage of one or more, particularly one or two, amino acids from the C-terminus of the heavy chain. Therefore, an antibody produced by a host cell by expression of a specific nucleic acid molecule encoding a full-length heavy chain may include the full-length heavy chain, or it may include a cleaved variant of the full-length heavy chain. This may be the case where the final two C-terminal amino acids of the heavy chain are glycine and lysine, respectively. Therefore, the C-terminal lysine, or the C-terminal glycine and lysine, of the Fc region may or may not be present. Thus, a “full-length heavy chain constant region” or a “full length antibody” for example, which is a human IgGl antibody, includes an IgGl with both a C-terminal glycine and lysine, without the C-terminal lysine, or without both the C-terminal glycine and lysine. Unless otherwise specified herein, numbering of amino acid residues in the Fc region or constant region is according to the EU numbering system, also called the EU index, as described in Kabat et al., Sequences ofProteins of Immunological Interest, 5thEd. Public Health Service, National Institutes of Health, Bethesda, MD, 1991.“Effector functions” refer to those biological activities attributable to the Fc region of an antibody, which vary with the antibody isotype. Examples of antibody effector functions include: Clq binding and complement dependent cytotoxicity (CDC); Fc receptor binding; antibody-dependent cell-mediated cytotoxicity (ADCC); phagocytosis; down regulation of cell surface receptors (e.g., B cell receptor); and B cell activation.The “class” of an antibody refers to the type of constant domain or constant region possessed by its heavy chain. There are five major classes of antibodies: IgA, IgD, IgE, IgG, and IgM, and several of these may be further divided into subclasses (isotypes), e.g., IgGl, IgG2, IgG3, IgG4, IgAl, and IgA2. The heavy chain constant domains that correspond to the different classes of immunoglobulins are called a, 5, 8, y, and p, respectively. The light chain of an antibody may be assigned to one of two types, called kappa (K) and lambda (X), based on the amino acid sequence of its constant domain.An “antibody fragment” refers to a molecule other than an intact antibody that comprises a portion of an intact antibody that binds the antigen (i.e., PAD4) to which the intact antibody binds. Examples of antibody fragments include but are not limited to Fv, Fab, Fab’, Fab’-SH, F(ab’)2; diabodies; linear antibodies; single-chain antibody molecules (e.g., scFv, and scFab); single domain antibodies (dAbs); and multispecific antibodies formed from antibody fragments. For a review of certain antibody fragments, see Holliger and Hudson, Nature Biotechnology 23: 1126-1136 (2005).The terms “full length antibody”, “intact antibody”, and “whole antibody” are used herein interchangeably to refer to an antibody having a structure substantially similar to a native antibody structure or, in the case of an IgG antibody, having heavy chains that contain an Fc region as defined herein above.The term “chimeric” antibody refers to an antibody in which a portion of the heavy and / or light chain is derived from a particular source or species, while the remainder of the heavy and / or light chain is derived from a different source or species.A “humanized” antibody refers to a chimeric antibody comprising amino acid residues from non-human CDRs and amino acid residues from human FRs. In certain aspects, a humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the CDRs correspond to those of a non- human antibody, and all or substantially all of the FRs correspond to those of a humanantibody. A humanized antibody optionally may comprise at least a portion of an antibody constant region derived from a human antibody. A “humanized form” of an antibody, e.g., a non-human antibody, refers to an antibody that has undergone humanization.The term “monoclonal antibody” as used herein refers to an antibody obtained from a population of substantially homogeneous antibodies, i.e., the individual antibodies comprising the population are identical and / or bind the same epitope, except for possible variant antibodies, e.g., containing naturally occurring mutations or arising during production of a monoclonal antibody preparation, such variants generally being present in minor amounts. In contrast to polyclonal antibody preparations, which typically include different antibodies directed against different determinants (epitopes), each monoclonal antibody of a monoclonal antibody preparation is directed against a single determinant on an antigen. Thus, the modifier “monoclonal” indicates the character of the antibody as being obtained from a substantially homogeneous population of antibodies and is not to be construed as requiring production of the antibody by any particular method.A “multispecific” antibody is one that binds specifically to more than one target antigen, while a “bispecific” antibody is one that binds specifically to two antigens. An “antibody conjugate” is an antibody conjugated to one or more heterologous molecule(s), including but not limited to a therapeutic agent or a label.“Percent (%) amino acid sequence identity” and “homology” with respect to a peptide, polypeptide or antibody sequence are defined as the percentage of amino acid residues in a candidate sequence that are identical with the amino acid residues in the specific peptide or polypeptide sequence, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity. Alignment for purposes of determining percent amino acid sequence identity can be achieved in various ways that are within the skill in the art, for instance, using publicly available computer software such as BLAST, BLAST-2, ALIGN or MEGALIGNTM (DNASTAR) software. Those skilled in the art can determine appropriate parameters for measuring alignment, including any algorithms needed to achieve maximal alignment over the full length of the sequences being compared.The term “signal sequence” or “leader sequence” refers to a sequence of amino acid residues located at the N terminus of a polypeptide that facilitates secretion of a polypeptide from a mammalian cell. A leader sequence may be cleaved upon export of the polypeptide from the mammalian cell, forming a mature protein. Leader sequences may be natural or synthetic, and they may be heterologous or homologous to the protein to which they areattached. Nonlimiting exemplary leader sequences also include leader sequences from heterologous proteins. In some embodiments, an antibody lacks a leader sequence. In some embodiments, an antibody comprises at least one leader sequence, which may be selected from native antibody leader sequences and heterologous leader sequences.The term “nucleic acid molecule” or “polynucleotide” includes any compound and / or substance that comprises a polymer of nucleotides. Each nucleotide is composed of a base, specifically a purine- or pyrimidine base (i.e. cytosine I, guanine (G), adenine (A), thymine (T) or uracil (U)), a sugar (i.e. deoxyribose or ribose), and a phosphate group. Often, the nucleic acid molecule is described by the sequence of bases, whereby said bases represent the primary structure (linear structure) of a nucleic acid molecule. The sequence of bases is typically represented from 5’ to 3’. Herein, the term nucleic acid molecule encompasses deoxyribonucleic acid (DNA) including e.g., complementary DNA (cDNA) and genomic DNA, ribonucleic acid (RNA), in particular messenger RNA (mRNA), synthetic forms of DNA or RNA, and mixed polymers comprising two or more of these molecules. The nucleic acid molecule may be linear or circular. In addition, the term nucleic acid molecule includes both sense and antisense strands, as well as single stranded and double stranded forms. Moreover, the herein described nucleic acid molecule can contain naturally occurring or non- naturally occurring nucleotides. Examples of non-naturally occurring nucleotides include modified nucleotide bases with derivatized sugars or phosphate backbone linkages or chemically modified residues. Nucleic acid molecules also encompass DNA and RNA molecules which are suitable as a vector for direct expression of an antibody of the invention in vitro and / or in vivo, e.g., in a host or patient. Such DNA (e.g., cDNA) or RNA (e.g., mRNA) vectors, can be unmodified or modified.An “isolated” nucleic acid refers to a nucleic acid molecule that has been separated from a component of its natural environment. An isolated nucleic acid includes a nucleic acid molecule contained in cells that ordinarily contain the nucleic acid molecule, but the nucleic acid molecule is present extrachromosomally or at a chromosomal location that is different from its natural chromosomal location.“Isolated nucleic acid encoding an anti-PAD4 antibody” refers to one or more nucleic acid molecules encoding anti-PAD4 antibody heavy and light chains (or fragments thereof), including such nucleic acid molecule(s) in a single vector or separate vectors, and such nucleic acid molecule(s) present at one or more locations in a host cell.The term “vector”, as used herein, refers to a nucleic acid molecule capable of propagating another nucleic acid to which it is linked. The term includes the vector as a selfreplicating nucleic acid structure as well as the vector incorporated into the genome of a host cell into which it has been introduced. Certain vectors are capable of directing the expression of nucleic acids to which they are operatively linked. Such vectors are referred to herein as “expression vectors”.The terms “host cell”, “host cell line”, and “host cell culture” are used interchangeably and refer to cells into which exogenous nucleic acid has been introduced, including the progeny of such cells.In this disclosure, “binds” or “binding” or “specific binding” and similar terms, when referring to a protein and its ligand or an antibody and its antigen target for example, or some other binding pair, means that the binding affinity between the members of the binding pair is sufficiently strong that the interaction cannot be due to random molecular associations (i.e. “nonspecific binding”). Such binding typically requires a dissociation constant (KD) of IpM or less, and may often involve a KD of 100 nM or less.“Affinity” refers to the strength of the sum total of noncovalent interactions between a single binding site of a molecule (e.g., an antibody) and its binding partner (e.g., an antigen). Unless indicated otherwise, as used herein, “binding affinity” refers to intrinsic binding affinity which reflects a 1 : 1 interaction between members of a binding pair (e.g., antibody and antigen). Affinity can generally be represented by the dissociation constant (KD). Affinity of an antibody for an antigen can be measured by common methods known in the art, such as surface plasmon resonance (SPR), for instance.“Treatment” as used herein, covers any administration or application of a therapeutic for disease in a human, and includes inhibiting the disease or progression of the disease or one or more disease symptoms, inhibiting or slowing the disease or its progression or one or more of its symptoms, arresting its development, partially or fully relieving the disease or one or more of its symptoms, or preventing a recurrence of one or more symptoms of the disease.An “autoimmune disease” or “autoimmune disorder,” as used herein, encompasses a disease characterized by the subject’s immune system attacking its own normal cells and tissues, and also encompasses immune-mediated diseases which may or may not be characterized by presence of auto-antibodies. The disclosure provides many nonlimiting examples of autoimmune diseases throughout. Some nonlimiting examples of autoimmune diseases include rheumatoid arthritis (RA), lupus (e.g., systemic lupus erythematosus (SEE)),lupus nephritis, vasculitis (e.g., ANCA-associated vasculitis), thrombosis (e.g, venous thrombosis), and inflammatory bowel disease (IBD) (e.g., ulcerative colitis, Crohn’s disease). The terms “disease” and “disorder” are used interchangeably herein. In some embodiments, the autoimmune disease is characterized by the presence of auto-antibodies. The term “effective amount” or “therapeutically effective amount” refers to an amount of a drug effective for treatment of a disease or disorder in a subject, such as to partially or fully relieve one or more symptoms. In some embodiments, an effective amount refers to an amount effective, at dosages and for periods of time necessary, to achieve the desired therapeutic or prophylactic result.Additional definitions of terms or phrases used herein are included in the sections that follow.II. Methods of Assessing CitrullinationThe present disclosure encompasses several methods of assessing the citrullination modifying activity of a PALM modulator or another therapeutic agent, and also of assessing citrullination of a biological sample from a subject, inter alia. The citrullination site or sites can be on proteins or peptides. In some cases, the peptides are peptide fragments of proteins, for instance, digested peptides that arise from enzymatic digestion of proteins. Thus, the expression “assessing citrullination of a citrullination site” encompasses assessing one citrullination site on one protein or peptide, as well as assessing more than one citrullination site on one protein or peptide, as well as assessing multiple citrullination sites. And accordingly, while the disclosure herein may recite a citrullination site on a protein or peptide, the “a” in this expression indicates “one or more” citrullination sites, and citrullination of more than one protein or peptide may also be assessed. Assessing multiple citrullination sites can encompass assessing citrullination sites on a plurality of proteins or on a plurality of peptides. For instance, the plurality of citrullination sites may be a plurality of citrullination sites on one protein or on peptide fragments of such protein, and / or the plurality of citrullination sites may be a plurality of citrullination sites on a plurality of different proteins or peptides. Although the methods of assessing citrullination disclosed herein may be used to assess citrullination at any citrullination site, in some embodiments, the citrullination site (e.g., the plurality of citrullination sites) is a citrullination site disclosed herein. Any and all such combinations are contemplated herein.Among the methods herein include, inter alia, a method of assessing citrullination at a citrullination site by mass spectrometry (MS). In some cases, the methods comprise assessment by liquid chromatography followed by MS (LC-MS). For example, liquid chromatography (e.g., HPLC, RPLC, nLC, pLC, or the like) may be used to separate peptides or proteins for analysis by MS. In some cases, the method comprises measuring, in a biological sample: (i) a first concentration of a citrullinated protein or a citrullinated peptide (which may be from a protein, e.g., a protein that has been enzymatically digested), wherein the citrullinated protein or citrullinated peptide is citrullinated at a citrullination site, and (ii) a second concentration of the corresponding total protein (which includes modified and unmodified forms of the protein) in the sample. In some embodiments, the concentration of corresponding total protein is measured by measuring a concentration of a signature peptide from the protein. The signature peptide is a peptide that is present both in modified and unmodified forms of the protein, and the signature peptide is a peptide that is not itself modified. Accordingly, when the concentration of signature peptide present in a sample within a well is measured by mass spectrometry, for example, the concentration of the signature peptide represents the well total concentration of the protein. In some embodiments, the method of measuring concentrations (i) and (ii) is by MS, such as LC-MS. In some embodiments, the method further comprises calculating a citrullination ratio. A “citrullination ratio,” as used herein, refers to a ratio of the first concentration (i) to the second concentration (ii). A citrullination ratio may be expressed in a variety of ways, for instance, as a percentage, or as any other fraction that is proportional to the aforementioned ratio of the first concentration to the second concentration.In some cases, the method comprises assessing citrullination of more than one citrullination site. Accordingly, the method can comprise measuring the first concentration and the second concentration for each of a plurality of (meaning two or more) different proteins or peptides that each contain a citrullination site. In some such cases, the method comprises measuring the first concentration and the second concentration for each of the plurality of proteins or peptides. In some such cases, at least two different peptides of the plurality are nonoverlapping fragments of the same protein and contain different citrullination sites; in those cases, the second concentration is the same for the peptides that are fragments of the same protein. In some cases, the method comprises calculating a ratio of the first concentration to the second concentration for each of the plurality of different proteins or peptides. Exemplary citrullination sites, proteins, and peptide fragments thereof arediscussed below and provided in Table A and Tables 3-18 herein. In some cases, the biological sample is obtained from a subject. In some cases, the biological sample is a whole blood, plasma, serum, blood supernatant, or synovial fluid sample. In other cases, the biological sample is a tissue sample. In some cases, the method further comprises comparing the first and second concentrations, or a ratio of the first and second concentrations to first and second concentrations or a ratio of first and second concentrations obtained from a control.In some cases where citrullination of a biological sample from a subject is assessed herein, the method further comprises determining one or more of the following based on the first and second concentrations or a ratio of the first and second concentrations: probability of a clinical outcome, risk for developing a citrullination-related disease, diagnosis of a citrullinati on-related disease, and selecting the subject from which the biological sample was derived for a treatment of a citrullination-related disease. For instance, in some cases, the subject either has a citrullination-related disease or may be at risk of developing a citrullination-related disease, and an assessment of citrullination in a biological sample, according to methods herein, may be used to confirm a diagnosis of such a disease, or to determine whether or not the subject is at risk of developing such a disease. In some cases, the method may allow for monitoring of citrullination in a subject’s biological samples, in order to determine a probability of clinical outcome, for example, based on comparison to reference subjects whose clinical outcomes are known, or to determine whether a PALM modulator or another therapeutic agent would be useful for treating the subject, or to determine if a PALM modulator or other therapeutic agent being currently administered to the subject is operating on the subject to reduce citrullination. Thus, for instance, in one example, the method further comprises determining, based on the first and second concentrations or a ratio of the first and second concentrations, whether the subject should receive treatment, for instance, in some cases, for a citrullination-related disease. In some cases, the method further comprises determining, based on the first and second concentrations or a ratio of the first and second concentrations, whether the subject should receive treatment with a therapeutic agent. Nonlimiting examples of such an agent include those that may be used for treatment of citrullination-related diseases, and those that target a biological pathway, such as, for example, NETosis or METosis, which may also involve PALM, such as, for example, an anti-histone antibody (e.g., CIT-013, for example), as well as PALM modulators, such as PALM inhibitors. In other cases, the method comprises determiningwhether a subject already receiving treatment with a therapeutic agent or other therapy should have the treatment adjusted, such as to increase or decrease a dose of a therapeutic agent being administered, or to start treatment with an agent such as a PAD4 modulator or an agent that targets a molecule involved in a biological pathway that involves PAD4. In some cases, the method further comprises determining whether a subject should receive treatment with a PAD4 modulator, or whether a subject already receiving treatment with a PAD4 modulator should have treatment adjusted, such as to increase or reduce the dose of the PAD4 modulator or to discontinue its use. In some cases, the PAD4 modulator is a PAD4 inhibitor. Exemplary PAD4 modulators are provided in this disclosure, and include, for example, therapeutic agents that can impact the expression or activity of PAD4, including the citrullination activity of PAD4. Such molecules include antibodies such as anti-PAD4 antibodies, as well as small molecules, such as small molecule PAD4 inhibitors, among others described in this disclosure.The present disclosure also encompasses a method of assessing the activity of a therapeutic agent, including, without limitation, an agent that may be used for treatment of a citrullination-related disease, an agent that targets a biological pathway involving PAD4, an agent that targets NETosis and / or METosis, an anti-histone antibody, and a PAD4 modulator such as a PAD4 inhibitor. Such therapeutic agents may, in some cases, comprise large molecules such as antibodies or fusion proteins, or may comprise small molecules. In some embodiments, a method of assessing the activity of a therapeutic agent, such as a PAD4 modulator, comprises assessing citrullination of a citrullination site on a protein or a peptide fragment thereof that is present in a biological sample from a subject. In such methods, the biological sample has been exposed to a PAD4 modulator or other therapeutic agent, either directly by adding it to the sample prior to assessment, or indirectly, by the subject having received at least one dose of the PAD4 modulator or other therapeutic agent prior to the sample being obtained. In some cases, the therapeutic agent being assessed is a PAD4 modulator. In some cases, the PAD4 modulator is a PAD4 inhibitor.In any of the methods described herein, in some embodiments, at least two different citrullination sites are assessed. In some cases, at least three different sites are assessed. In some cases, at least four different sites are assessed. In some cases, citrullination of at least two different proteins is assessed. In some cases, citrullination of at least three different proteins is assessed. In some cases, citrullination of at least four different proteins isassessed. In some cases, citrullination of 2-4 citrullination sites and / or 2-4 different proteins is assessed.In any of the methods herein, in some cases the protein comprising the citrullination site for assessment is selected from one or more of: alpha-2-HS-glycoprotein, alpha-2- macroglobulin, albumin, antithrombin-III, apolipoprotein A-I, apolipoprotein A-IV, apolipoprotein B-100, apolipoprotein E, apolipoprotein LI, C4b-binding protein alpha chain, ceruloplasmin, clusterin, complement C2, complement C3, complement C4-A, complement C4-B, complement factor B, complement factor H, complement factor I, complement component C9, fibrinogen alpha chain, fibrinogen beta chain, fibrinogen gamma chain, fibronectin, galectin-3 -binding protein, gelsolin, haptoglobin, haptoglobin-related protein, hemopexin, immunoglobulin heavy variable 1-3, immunoglobulin heavy variable 1-8, immunoglobulin heavy variable 1-46, immunoglobulin heavy variable 1-69, immunoglobulin heavy variable 1-69D, inter-alpha-trypsin inhibitor heavy chain H4, immunoglobulin lambdalike polypeptide 1, immunoglobulin heavy constant mu, inter-alpha-trypsin inhibitor heavy chain H2, isoform 2 of complement C4-A, plasminogen, plasminogen-like protein A, alpha- 1-microglobulin / bikunin precursor, prothrombin, proteoglycan 4, serotransferrin, serum amyloid A-l protein, serum amyloid A-2 protein, serum amyloid A-4 protein, stromelysin- 1, vitamin D-binding protein, and vitronectin. Thus, in some embodiments, a citrullination site from a protein above, or a peptide fragment thereof, is assessed. For example, in some embodiments, the method herein comprises a method of assessing the activity of a PAD4 modulator or other therapeutic agent, the method comprising assessing citrullination of a citrullination site on a protein or a peptide fragment thereof that is present in a biological sample from a subject, wherein the biological sample has been exposed to a PALM modulator or other therapeutic agent, and optionally wherein the protein is selected from one or more of those listed above, or wherein the protein is selected from one or more of those listed in Table A below.In some cases, the citrullination site to be assessed is selected from one or more citrullination sites shown in Table A below. In the table below, the amino acid residue corresponding to a citrullination site is noted in the left column, with a reference accession number that may be used to locate the citrullination site in the publicly available UniProt database is listed in the right column. The UniProt accession number for each protein listed is provided in the table. The public database provides an amino acid and gene sequence corresponding to the accession number (e.g., P01023 for alpha-2-macroglobulin). It isunderstood that each of the proteins listed in the table below may have more than one naturally occurring amino acid sequence. Different isoforms of a protein can arise, for instance, due to the natural occurrence of different alleles reflecting substitutions, insertions, and / or deletions in the amino acid sequence, as well as due to alternative promoters, splicing and / or translation initiation sites. Accordingly, the accession number and its associated sequence listed for a given protein in Table A, and also in further tables herein that also provide citrullination sites and reference protein accession numbers or sequences, is merely a reference, which may be used to identify the citrullination site in a protein having the same sequence as the reference sequence as well as to identify the citrullination site in a naturally occurring variant protein, for example, by alignment of the variant sequence against the reference sequence. In some embodiments only one of the citrullination sites of Table A is assessed, while in other cases, at least two, at least three, at least five, at least ten, at least twenty, or at least fifty of the sites are assessed, such as 2-5, 2-10, 2-20, 2-50, 10-50, 5-50, 10-50, or 5-20 of the sites are assessed. In some cases, citrullination sites of only one protein are assessed, while in other cases, citrullination sites of two or more proteins, such as at least 2, 3, 5, 6, 7, or 8 proteins are assessed. In some cases, citrullination sites of 2-5, 2-10, 5-10, 2-20, 5-10, or 10-20 different proteins are assessed.Table A, provided below, for example, lists exemplary citrullination sites, i.e., a residue of a particular human protein that may be citrullinated in a biological sample, and in the right column, lists the site as located within the protein sequence that is published in the UniProt database (accessible at www.uniprot.org).Table A - Exemplary Citrullination SitesIn some cases, the citrullination site is a site designated by underlining on one or more peptides shown in Tables 3-18. In some cases, the method comprises assessing citrullination of a peptide fragment of a protein, wherein the sequence of the peptide fragment comprises a peptide sequence shown in any one of Tables 3-18. In some cases, the method comprises assessing citrullination of a peptide fragment of a protein, wherein the sequence of the peptide fragment comprises a peptide sequence shown in Table 3. In some cases at least twopeptide sequences as shown in Table 3 are assessed, such as 2, 3, 4, or all shown in Table 3. In some cases, the method comprises assessing citrullination of a peptide fragment, wherein the sequence of the peptide fragment comprises a peptide sequence shown in Table 4. In some cases at least two peptide fragment sequences as shown in Table 4 are assessed, such as 2, 3, 4, or all shown in Table 4. In some cases, the method comprises assessing citrullination of a peptide fragment, wherein the sequence of the peptide fragment comprises a peptide sequence shown in Table 5. In some cases at least two peptide fragment sequences as shown in Table 5 are assessed, such as 2, 3, 4, or all shown in Table 5. In some cases, the method comprises assessing citrullination of a peptide fragment, wherein the sequence of the peptide fragment comprises a peptide sequence shown in Table 6. In some cases at least two peptide fragment sequences as shown in Table 6 are assessed, such as 2, 3, 4, or all shown in Table 6. In some cases, the method comprises assessing citrullination of a peptide fragment, wherein the sequence of the peptide fragment comprises a peptide sequence shown in Table 7. In some cases at least two peptide fragment sequences as shown in Table 7 are assessed, such as 2, 3, 4, or all shown in Table 7. In some cases, the method comprises assessing citrullination of a peptide fragment, wherein the sequence of the peptide fragment comprises a peptide sequence shown in Table 8. In some cases at least two peptide fragment sequences as shown in Table 8 are assessed, such as 2, 3, 4, or all shown in Table 8. In some cases, the method comprises assessing citrullination of a peptide fragment, wherein the sequence of the peptide fragment comprises a peptide sequence shown in Table 9. In some cases at least two peptide fragment sequences as shown in Table 9 are assessed, such as 2, 3, 4, or all shown in Table 9. In some cases, the method comprises assessing citrullination of a peptide fragment, wherein the sequence of the peptide fragment comprises a peptide sequence shown in Table 11. In some cases at least two peptide fragment sequences as shown in Table 11 are assessed, such as 2, 3, 4, or all shown in Table 11. In some cases, the method comprises assessing citrullination of a peptide fragment, wherein the sequence of the peptide fragment comprises a peptide sequence shown in Table 11. In some cases at least two peptide fragment sequences as shown in Table 11 are assessed, such as 2, 3, 4, or all shown in Table 11. In some cases, the method comprises assessing citrullination of a peptide fragment, wherein the sequence of the peptide fragment comprises a peptide sequence shown in Table 12. In some cases at least two peptide fragment sequences as shown in Table 12 are assessed, such as 2, 3, 4, or all shown in Table 12. In some cases, the method comprises assessing citrullination of a peptide fragment, wherein the sequence of the peptide fragment comprises a peptidesequence shown in Table 13. In some cases at least two peptide fragment sequences as shown in Table 13 are assessed, such as 2, 3, 4, or all shown in Table 13. In some cases, the method comprises assessing citrullination of a peptide fragment, wherein the sequence of the peptide fragment comprises a peptide sequence shown in Table 14. In some cases at least two peptide fragment sequences as shown in Table 14 are assessed, such as 2, 3, 4, or all shown in Table 14. In some cases, the method comprises assessing citrullination of a peptide fragment, wherein the sequence of the peptide fragment comprises a peptide sequence shown in Table 15. In some cases at least two peptide fragment sequences as shown in Table 15 are assessed, such as 2, 3, 4, or all shown in Table 15. In some cases, the method comprises assessing citrullination of a peptide fragment, wherein the sequence of the peptide fragment comprises a peptide sequence shown in Table 16. In some cases at least two peptide fragment sequences as shown in Table 16 are assessed, such as 2, 3, 4, or all shown in Table 16. In some cases, the method comprises assessing citrullination of a peptide fragment of a protein, wherein the sequence of the peptide fragment comprises a peptide sequence shown in Table 17. In some cases at least two peptide sequences as shown in Table 17 are assessed, such as 2, 3, 4, or all shown in Table 17. In some cases, the method comprises assessing citrullination of a peptide fragment, wherein the sequence of the peptide fragment comprises a peptide sequence shown in Table 18. In some cases at least two peptide fragment sequences as shown in Table 18 are assessed, such as 2, 3, 4, or all shown in Table 18.Proteins or peptides that are assessed for citrullination may, in some cases, contain chemical modifications other than citrullination, such as carbamidomethylation of cysteines, oxidation of methionines, and modifications of the N-terminus, among others. Such chemical modifications can be detected, for instance, by mass spectrometry.In some cases, the citrullination site is selected from one or more of the following: R1391 of proteoglycan 4 (corresponding to arginine residue R1391 of the protein sequence found in the UniProt database under accession number Q92954), R573 of fibrinogen alpha chain (corresponding to R573 of P02671), R591 of fibrinogen alpha chain (corresponding to R591 of P02671), R573 of complement C3 (corresponding to R573 of P01024), R688 of inter-alpha-trypsin inhibitor heavy chain H4 (corresponding to R688 of Q14624), R297 of protein AMBP (corresponding to R297 of P02760), R715 of alpha-2-macroglobulin (corresponding to R715 of PO 1023), R32 of gel solin (corresponding to R32 of P06396), R59 of haptoglobin (corresponding to R59 of P00738), and R651 of serotransferrin (corresponding to R651 of P02787), wherein all of the code names beginning with Q or Pfollowed by a number are UniProt accession numbers for the proteins. In some cases, these citrullination sites may be assessed from one or more peptide fragments of a protein, wherein the sequences of the peptide fragments comprise (where the citrullination site is bold and underlined): AITTRSGQTLSK (SEQ ID NO: 247), ESSSHHPGIAEFPSRGK (SEQ ID NO:248), QFTSSTSYNRGDSTFESK (SEQ ID NO: 249), SGQSEDRQPVPGQQMTLK (SEQ ID NO: 250), ASHLGLARSNLDEDIIAEENIVSR (SEQ ID NO: 251), QLGLPGPPDVPDHAAYHPFRR (SEQ ID NO: 252), GPCRAFIQLWAFDAVK (SEQ ID NO: 253), VGFYESDVMGRGHAR (SEQ ID NO: 254), ATASRGASQAGAPQGR (SEQ ID NO: 255), LRTEGDGVYTLNDK (SEQ ID NO: 256), or DLLFRDDTVCLAK (SEQ ID NO: 257). In some cases, the citrullination site is assessed on one or more peptide fragments of a protein, wherein the sequences of the peptide fragments comprise (where the citrullination site is bold and underlined): AITTRSGQTLSK (SEQ ID NO: 247), ESSSHHPGIAEFPSRGK (SEQ ID NO: 248), QFTSSTSYNRGDSTFESK (SEQ ID NO:249), SGQSEDRQPVPGQQMTLK (SEQ ID NO: 250), QLGLPGPPDVPDHAAYHPFRR (SEQ ID NO: 252), or GPCRAFIQLWAFDAVK (SEQ ID NO: 253). In some cases, the citrullination site is one or more of the following: R715 of alpha-2-macroglobulin (corresponding to R715 of P01023), R297 of protein AMBP (corresponding to R297 of P02760), R250 of clusterin (corresponding to R250 of Pl 0909-2), R23 of clusterin (corresponding to R23 of P10909-3), R165 of clusterin (corresponding to R165 of P10909-4), R209 of clusterin (corresponding to R209 of Pl 0909-5), R178 of clusterin (corresponding to R178 of Pl 0909-6), R198 of clusterin (corresponding to R198 of Pl 0909), R32 of gelsolin (corresponding to R32 of P06396), R59 of haptoglobin (corresponding to R59 of P00738-2 or P00738), R60 of haptoglobin-related protein (corresponding to R60 of P00739), R97 of haptoglobin-related protein (corresponding to R97 of P00739-2), or R651 of serotransferrin (corresponding to R651 of P02787). In any of the above cases, in some embodiments only one member within of the above groups of citrullination sites is assessed, while in other cases, at least two, at least three, at least five, and in the larger groups above, at least ten, or at least twenty of the sites are assessed, such as from 2-5, or from 2-10, or from 2 to all of the sites are assessed. In some cases, citrullination sites on only one protein are assessed, while in other cases, citrullination sites on two or more proteins, such as 2-5, 2-10, 5-10, 2-20, 5-10, or 10-20 different proteins. In some such cases, the biological sample is a whole blood, serum, plasma, blood supernatant, or synovial fluid sample. In some such cases, the biological sample is a whole blood, serum, plasma, or blood supernatant sample.In some cases in which the biological sample comprises synovial fluid, the citrullination site to be assessed is selected from one or more citrullination sites shown in Table 11. In some cases at least two peptide fragment sequences as shown in Table 11 are assessed, such as 2, 3, 4, or all shown in Table 11. In some such cases, the citrullination site selected from one or more citrullination sites shown in Table 11, or is a citrullination site located on a peptide fragment comprising one of the following sequences, wherein the citrullination site is designated by underlining: AITTRSGQTLSK (SEQ ID NO: 247), ESSSHHPGIAEFPSRGK (SEQ ID NO: 248), QFTSSTSYNRGDSTFESK (SEQ ID NO: 249), SGQSEDRQPVPGQQMTLK (SEQ ID NO: 250), QLGLPGPPDVPDHAAYHPFRR (SEQ ID NO: 252), or GPCRAFIQLWAFDAVK (SEQ ID NO: 253). In some cases at least two peptide fragment sequences as shown in Table 11 are assessed, such as 2, 3, 4, or all shown in Table 11.In some cases, the protein of interest comprises fibrinogen alpha chain and / or gelsolin. In such cases, the citrullination site for assessment may comprise the fibrinogen citrullination site located at R591 of P02671, which in some cases may be assessed via a peptide of sequence QFTSSTSYNRGDSTFESK (SEQ ID NO: 249), wherein the R is the citrullination site. In some cases, the citrullination site for assessment may comprise the gelsolin citrullination site located at R32 of P06396, which in some cases may be assessed via a peptide of sequence ATASRGASQAGAPQGR (SEQ ID NO: 255), wherein the underlined R is the citrullination site. In some cases in which the citrullination site is from fibrinogen and / or gelsolin, the sample is a whole blood, serum, plasma, blood supernatant, or synovial fluid sample. In some such cases, the sample is a whole blood, serum, plasma, or blood supernatant sample.The “assessing” in methods herein encompasses a variety of ways of examining citrullination, such as, without limitation, qualitatively determining whether citrullination has occurred at a particular citrullination site on a protein or peptide, and quantitatively determining citrullination of a protein or a peptide. In some embodiments, the assessing comprises quantitatively determining citrullination at a particular citrullination site (e.g., a citrullination site disclosed herein). In some embodiments, quantitatively determining citrullination at a particular citrullination site comprises determining a “citrullination ratio” as defined above.In some cases, mass spectrometry (MS) is used to assess citrullination at a citrullination site. MS can detect differences between the molecular weights of a protein orpeptide that is citrullinated and the corresponding protein or peptide that is not citrullinated. As described herein in the examples, intensity measurements obtained with MS can be used to measure the concentration of a citrullinated peptide. MS can also be used to measure the total concentration of corresponding protein from which a citrullinated peptide is derived. For instance, such total concentration of protein can be measured by measuring the concentration of a signature peptide. As used herein, such a “signature peptide” is a peptide that is not modified and is present in both modified and unmodified forms of the protein; accordingly, the concentration of the signature peptide represents the concentration of the corresponding total protein, including modified and unmodified forms of the protein. For example, in the case of FGA, an exemplary signature peptide is GSESGIFTNTK (SEQ ID NO: 258; amino acids 548-558). This peptide is not post-translationally modified in human matrices tested, is in the near vicinity of citrullinated peptides ESSSHHPGIAEFPSRGK (SEQ ID NO: 248; amino acids 559-575) and QFTSSTSYNRGDSTFESK (SEQ ID NO: 249; amino acids 582-600), and accordingly, it accurately represents total FGA protein concentration. Selection of signature peptides is known in the art and is described, for instance, in Qiu, X.I. et al. Signature peptide selection workflow for biomarker quantification using LC-MS based targeted proteomics. Bioanalysis (11 April 2023) 10.4155 / bio-2022- 0241 C In some cases, assessing citrullination of the citrullination site comprises performing liquid chromatography to assist in separating protein or peptide species, followed by mass spectrometry (LC-MS). For example, liquid chromatography (e.g., HPLC, RPLC, nLC, pLC, or the like) may be used to separate peptides or proteins for analysis by MS.In methods herein, a sample may be assessed directly after being obtained, or alternatively, a sample may be first prepared in some fashion prior to assessment of citrullination, for example, in order to improve the detection of the proteins or peptides of interest in the sample. For instance, a sample may be diluted with a buffer, a sample comprising cells may be treated to lyse the cells or to separate the cells from the sample fluid such as by centrifugation or filtration. For example, a protein of interest or peptide fragments thereof may first be enriched by separating them from other components of the starting sample prior to assessment of citrullination. For instance, one method of enriching a protein or peptide of interest is to isolate it from the sample. Thus, such a protein or peptide could be exposed to an affinity reagent such as an antibody and thus targeted for purification or removal from the sample. In some cases, such an affinity reagent may be immobilized on a solid surface such as a bead, chip, plate, or well of a plate, in order to facilitate suchenrichment. In some cases, the proteins of the sample may also be enzymatically digested to form peptide fragments, may be denatured to remove tertiary structure, and / or a sample may be diluted or treated to remove or separate certain components prior to assessment. In some cases, other components could be degraded or removed from the sample, such as nucleic acids for instance, by enzymatic degradation or by alcohol precipitation.In some cases, a sample may also be treated so as to promote release of endogenous PAD4 in the sample prior to assessment, or may be contacted with exogenous PAD4 to boost the signal from the sample, among other optional treatments. In some cases, for instance in order to boost the overall PAD4 activity in the biological sample, the sample may be incubated with exogenous PAD4 prior to assessing citrullination. For example, in some cases, a concentration of from 5 nM to 15 nM PAD4 may be added, such as from 7nM to 14 nM, from 7 nM to 10 nM, from 10 nM to 15 nM, In some cases, a concentration of 10 nM exogenous PAD4 or about 10 nM exogenous PAD4 is added. In some cases, exogenous calcium ion (Ca2+) is also added to the sample. In some cases, where citrullination from additional PAD proteins is also assessed, those may also be added exogenously, such as PAD2, which could be added, for example, at concentrations of 2-4 nM, such as at 3 nM or about 3 nM. In other cases, the sample is not exposed to exogenous PAD4 or is not exposed to any exogenous PAD proteins. Thus, in some cases, all PAD4 activity in a biological sample is from endogenous PAD4 present in the sample. In some instances, the biological sample may be incubated for a period, which in some cases may induce the release of endogenous PAD4 within the sample. Such incubation may be for at least 12 hours, at least 18 hours, 12-96 hours, 24-96 hours, 24-72 hours, 24-36 hours, 36-96 hours, 36-72 hours, 48- 96 hours, 48-72 hours, 60-96 hours, 48-60 hours or 60-72 hours. In some cases, the incubation is for 48-96 hours. In some cases, such incubation is conducted at 34-40 °C, such as at 36-39 °C, 36-38 °C, or 37 °C. In some cases, the incubation is conducted in a TruCulture® null tube (Rules Based Medicine, Austin, TX), or a similar container comprising culture media for preservation or analysis of biological samples. In some cases where the method involves assessing an exogenous PAD4 modulator, the PAD4 modulator may be added before the incubation of the sample. In other cases, a PAD4 modulator is added after the incubation. Where exogenous PAD4 is added to a sample, the sample may also be incubated with the exogenous PAD4, such as for 1-3 hours, or 1-2 hours, or 1, 2, or 3 hours, prior to assessing citrullination. In some cases, such incubation is conducted at 34-40 °C, such as at 36-39 °C, 36-38 °C, or 37 °C. In some cases, both exogenous PAD4 and anexogenous PAD4 modulator may be added together. In other cases, a PAD4 modulator may be added after the incubation with exogenous PAD4. In some cases an incubation is conducted in a CO2 incubator. In some cases, the activity of exogenous PAD4 added to a sample is quenched by adding EDTA to the sample. Thus, for example, in some cases the method comprises adding EDTA to the biological sample after incubation with the exogenous PAD4 in order to quench the activity of the PAD4.In some cases, prior to analysis, a sample could be treated to expose one or more proteins or peptide fragments thereof comprising citrullination sites for later assessment. For example, proteins in a sample may be denatured or digested with enzymes. For instance, proteins may be denatured to remove tertiary structure, for example, by incubation at above physiological temperatures, such as at 60-90°C, such as 60-80°C, 70-85°C, or 80°C, for a period of 5-30 minutes, such as 10-30, 10-20, 15-25, or 20 minutes. In other cases, a chemical denaturant such as urea could be applied. A proteolytic enzyme such as trypsin, LysC, rLysC, LysN, GluC, AspN, rAspN, or a combination of proteolytic enzymes, such as more than one of trypsin, LysC, rLysC, LysN, GluC, AspN, and rAspN, could be used for enzymatic digestion, for example, to form peptide fragments of proteins of interest for later assessment.Accordingly, overall, there are a variety of ways in which a sample may be prepared for assessment of citrullination herein.In embodiments herein in which assessment of citrullination of a biological sample is used to assess a PAD4 modulator or other therapeutic agent, there are also several ways in which the biological sample may be exposed to the PAD4 modulator or other therapeutic agent herein. In some cases, a sample is directly incubated with a PAD4 modulator or other therapeutic agent (i.e., an exogenous PAD4 modulator), such as by contacting the biological fluid with the PAD4 modulator or other therapeutic agent ex vivo. In other cases, the biological sample has been exposed to a PAD4 modulator or other therapeutic agent in vivo in a subject as a result of the PAD4 modulator or other therapeutic agent being administered to the subject. For example, a PAD4 modulator or a metabolite thereof may travel through blood, serum, plasma, or synovial fluid or other bodily fluids or tissues after administration to a subject, or may contact cells in the body which in turn travel to such fluids or to certain bodily tissues.A biological sample herein may comprise biological fluid (i.e., a biological fluid sample), such as, without limitation, blood, plasma, serum, blood supernatant, synovial fluid,lymph, pleural fluid, interstitial fluid, sweat, tears, sputum, or urine. In other cases, a biological sample may comprise tissue, such as from a joint, a neoplasm, or a tumor. In some methods herein, the biological sample comprises synovial fluid. In some methods, the biological sample comprises blood or is derived from blood; in some cases the biological sample comprises serum, plasma, or blood supernatant (e.g. a supernatant that forms after centrifugation or filtration of blood). In some cases, the biological sample is fresh, meaning that it has not been frozen and thawed prior to use. In other cases, the sample has been frozen and thawed before use in the method. Thus, in some cases the method comprises freezing and thawing the biological sample before assessing citrullination of the citrullination site. For example, the sample may be frozen at a temperature of -70 °C or below, or -80 °C or below. In some embodiments, the biological sample is prepared for assessment prior to the assessing, such as according to methods provided above. For instance, in some cases the sample is treated by enzymatically digesting proteins, such as with one or more protease enzymes. In some cases, proteins comprising citrullination sites are enriched, in some cases by being removed from the sample, such as with an antibody or affinity reagent, and / or in some cases other proteins or contaminants are removed from the sample. For example, in some cases an antibody that specifically binds to the protein to be assessed may be used to enrich that protein for later assessment of citrullination. In some cases, the antibody or affinity reagent may be immobilized, such as placed on a matrix such as a bead or chip or well of a plate, other solid surface. In some cases, the biological sample may be diluted before assessment of citrullination. In some cases, proteins in the biological sample may be denatured to remove tertiary structure prior to assessment of citrullination. In some cases, any combination of the above treatments may be conducted on the sample.In some cases, assessing citrullination of a citrullination site comprises measuring a citrullination ratio, as described above. In some cases, the method comprises comparing the citrullination assessment, such as a citrullination ratio or the concentration of a citrullinated protein or peptide fragment thereof, to that of a reference or control. For example, in some cases, the comparison is to a reference citrullination ratio, which may be obtained, for example, from a reference sample, or which may be a value or range of values that represents those obtained from reference samples. Accordingly, in some cases, the method comprises assessing comprises determining a difference between the citrullination ratio for the biological sample and a reference citrullination ratio.The terms “reference” and “control,” when referring to a biological sample, are used interchangeably to refer to a biological sample against which a measurement from a sample at interest is compared. In some cases, such a control is a sample that has not been exposed to PAD4 but is otherwise comparable to the sample of interest. In some cases, the control is a “baseline” sample, which is a sample taken from a subject prior to some event of interest, such as prior to treatment with a therapeutic agent, e.g., PAD4 modulator, and which, for instance, may be compared to a sample from the same subject taken after the event, such as after treatment with the therapeutic agent. In some cases, the control is a sample from the subject taken prior to treatment with a PAD4 modulator. In some cases, the control is a sample from the subject taken prior to a change in PAD4 modulator treatment. Accordingly, in some cases, one may determine how treatment with a PAD4 modulator impacts a subject by comparing to such a baseline control sample. In other cases, the control biological sample has been exposed to a different treatment than the biological sample, such as to a different PAD4 modulator or different therapeutic agent than the biological sample. In some cases, the control biological sample has been exposed to a different dose of the PAD4 modulator or other therapeutic agent than the biological sample. In some cases, the control is a sample from a healthy subject, which, for instance, could be compared to a sample from a subject with a disorder, or a subject following treatment with PAD4. In other cases, a control biological sample is a sample that has been exposed to a different therapeutic agent or PAD4 modulator, or to a different dose of the same therapeutic agent or PAD4 modulator as the sample of interest. Thus, in some embodiments, citrullination assessments are compared to those of one or more control samples (e.g., baseline samples or samples from other points of time from the same subject, or samples from other subjects), or to values associated with one or more control samples (e.g., from a pool of healthy subjects). For example, in some cases, a citrullination assessment from a biological sample herein may be controlled to a group of control samples representing typical values found in a particular type of subject, or representing values found across a range of subjects.In some embodiments, the present disclosure includes methods of assessing citrullination in a biological sample of a subject comprising assessing citrullination of a citrullination site on a protein or a peptide fragment thereof that is present in the biological sample. In some cases, the subject has not received treatment with any PALM modulator. In other cases, the subject has received treatment with a PALM modulator. In some cases, the subject has not received treatment with any therapeutic agent. In other cases, the subject hasreceived treatment with a therapeutic agent. The present disclosure also encompasses methods of assessing the activity of a PAD4 modulator or other therapeutic agent comprising obtaining a biological sample from a subject following treatment of the subject with at least one dose of a PAD4 modulator or other therapeutic agent, and assessing citrullination of a citrullination site on a protein or a peptide fragment thereof that is present in the biological sample. In some cases, these methods further comprises comparing the assessment of the citrullination to that of a control biological sample, such as described above. In some cases, where the subject has been treated with a PAD4 modulator or other therapeutic agent, the control biological sample is a baseline sample obtained from the subject prior to treatment with the PAD4 modulator or other therapeutic agent. In some cases, the method comprises obtaining a baseline biological sample from the subject prior to treatment with the PAD4 modulator or other therapeutic agent, and assessing citrullination of a citrullination site on a protein or a peptide fragment thereof that is present in the baseline biological sample, and optionally comparing the assessed citrullination (e.g. a citrullination ratio) of the biological sample and the baseline biological sample. In some cases, a citrullination assessment is performed in order to determine if a subject should receive treatment with a PAD4 modulator, or to serve as a baseline for later monitoring of citrullination following treatment with a PAD4 modulator or other therapeutic agent.In some cases, the method comprises (a) contacting a biological sample from a subject with exogenous PAD4, and (b) assessing citrullination of a citrullination site on a protein or a peptide fragment thereof that is present in the sample. In some cases, the sample is a biological fluid sample, such as plasma or serum, blood supernatant, whole blood, or synovial fluid. In some cases, it is plasma or serum. In some cases, the biological sample is prepared as described above prior to the assessing. In some cases, the concentration of exogenous PAD4 may be as provided above (e.g., from 5 nM to 15 nM PAD4, such as from 7nM to 14 nM, from 7 nM to 10 nM, from 10 nM to 15 nM). In some cases, another PAD protein (e.g., PAD2) is also added. In some cases, calcium ion (Ca2+) is also added to the sample. For instance, in some cases, the sample is treated to enrich a protein of interest, and / or to denature and / or enzymatically digest proteins of interest for later assessment, and / or to deplete proteins such as serum albumin. In some cases, the protein of interest is enriched by immunoenrichment techniques such as described below, for example, which may comprise using affinity reagents to isolate or remove the protein of interest.In some embodiments, the methods comprise in vitro methods of assessing the activity of a PAD4 modulator or other therapeutic agent, comprising (a) treating a biological sample from a subject with a PAD4 modulator or other therapeutic agent to form a treated biological sample, and after the treating, (b) assessing citrullination of a citrullination site on a protein or a peptide fragment thereof that is present in the biological sample. In some cases, such methods further comprise assessing citrullination of the citrullination site on the protein or a peptide fragment in a control biological sample, such as described above. Methods herein also comprise, for example, an in vitro method of assessing the activity of a PAD4 modulator or other therapeutic agent, comprising (i) dividing a biological sample obtained from a subject into a plurality of biological samples, (ii) contacting each of the plurality of biological samples with a different dose of the PAD4 modulator or other therapeutic agent, and (iii) assessing, for each of the plurality of biological samples, citrullination of a PAD4- dependent citrullination site on a protein or peptide fragment thereof that is present in the biological sample. In some cases, such a method comprises calculating an IC50 for the PAD4 modulator or other therapeutic agent based on the outcome of the assessing. Methods herein can also include, for example, an in vitro method of assessing citrullination by endogenous PAD4, comprising incubating the biological sample (or the plurality of biological samples) from the subject for an incubation period (for example, to trigger release of endogenous PAD4) and assessing citrullination of a citrullination site on a protein or peptide fragment thereof that is present in the sample. Methods herein also include, for example, an in vitro method of assessing citrullination by endogenous PAD4, comprising (a) incubating a whole blood sample from a subject at 34-40°C for an incubation period (for example, to trigger release of endogenous PAD4), (b) after the incubation period, separating plasma or supernatant from the whole blood sample, and (c) assessing citrullination of a citrullination site on a protein or peptide fragment thereof that is present in the plasma or supernatant. In some cases, the incubating is in a TruCulture® null tube. Such incubation may be for at least 12 hours, at least 18 hours, 12-96 hours, 24-96 hours, 24-72 hours, 24-36 hours, 36-96 hours, 36-72 hours, 48-96 hours, 48-72 hours, 60-96 hours, 48-60 hours or 60- 72 hours. In some cases, the incubation period is 48 to 96 hours. In some cases, the incubating is at a temperature of 35 to 40°C, at a temperature of 36 to 39°C, at a temperature of 36 to 38°C, or at a temperature of 37°C. In some cases, the sample is prepared for assessment of citrullination, such as to enrich the protein or peptide to be assessed. In some cases, the method comprises, for example, separating the plasma or supernatant from thewhole blood sample, such as by centrifuging or filtering the whole blood sample. These methods may also comprise (i) incubating the plasma or supernatant with a protein depletion resin, and (ii) recovering depleted plasma or supernatant that has flowed through the resin to obtain depleted flowthrough, optionally wherein the recovering comprises centrifugation. They may also comprise enzymatically digesting polypeptides in the depleted flowthrough before the assessing, and optionally cleaning up enzymatically digested peptides, such as with an iST-BCT kit (PreOmics, Planegg / Martinsried, Germany) or a similar kit, for instance. Such kits may be used in some embodiments to purify a sample prior to MS analysis and / or to minimize artificial protein modifications induced by reagents added to a sample, such as deamidation and oxidation modifications. In some cases, the whole blood sample has not been frozen and thawed. In other cases, the whole blood sample has been frozen and thawed. In some cases, the method comprises freezing the plasma or supernatant after it has been separated from the whole blood and subsequently thawing the plasma or supernatant before the assessing.The disclosure herein also encompasses an in vitro method of assessing changes in citrullination in a subject, comprising (a) incubating a whole blood sample from a subject at 34-40°C for an incubation period (such as at a temperature of 36 to 39°C, at a temperature of 36 to 38°C, or at a temperature of 37°C for at least 12 hours, at least 18 hours, 12-96 hours, 24-96 hours, 24-72 hours, 24-36 hours, 36-96 hours, 36-72 hours, 48-96 hours, 48-72 hours, 60-96 hours, 48-60 hours or 60-72 hours), wherein the sample is obtained from the subject following administration of a PALM modulator to the subject, (b) after the incubation period, separating plasma or supernatant from the whole blood sample, and (c) assessing citrullination of a citrullination site on a protein or peptide fragment thereof that is present in the plasma or supernatant. In some cases, the method further comprises (d) incubating a second whole blood sample from the subject at 34-40°C for an incubation period (such as at a temperature of 36 to 39°C, at a temperature of 36 to 38°C, or at a temperature of 37°C for at least 12 hours, at least 18 hours, 12-96 hours, 24-96 hours, 24-72 hours, 24-36 hours, 36-96 hours, 36-72 hours, 48-96 hours, 48-72 hours, 60-96 hours, 48-60 hours or 60-72 hours), wherein the second whole blood sample is obtained from the subject before administration of the PAD4 modulator to the subject, € after the incubation period, separating plasma or supernatant from the second whole blood sample, and (f) assessing citrullination of a citrullination site on a protein or peptide fragment thereof that is present in the plasma or supernatant from the second whole blood sample. In some cases, an outcome of the assessingin step (f) is compared with an outcome of the assessing in step (c). Methods herein also include, for example, a method of assessing effects of a PAD4 modulator, the method comprising (a) exposing a whole blood sample from a subject to a PAD4 modulator in vitro, (b) incubating the whole blood sample at 34-40°C for an incubation period (such as at a temperature of 36 to 39°C, at a temperature of 36 to 38°C, or at a temperature of 37°C for at least 12 hours, at least 18 hours, 12-96 hours, 24-96 hours, 24-72 hours, 24-36 hours, 36-96 hours, 36-72 hours, 48-96 hours, 48-72 hours, 60-96 hours, 48-60 hours or 60-72 hours), (c) after the incubation period, separating plasma or supernatant from the whole blood sample, and (d) assessing citrullination of a citrullination site on a protein or peptide fragment thereof that is present in the plasma or supernatant. In some embodiments, the method further comprises performing a parallel set of steps on at least one control whole blood sample. In some embodiments, the method further comprises (e) incubating a control whole blood sample at 34-40°C for an incubation period (such as at a temperature of 36 to 39°C, at a temperature of 36 to 38°C, or at a temperature of 37°C for at least 12 hours, at least 18 hours, 12-96 hours, 24-96 hours, 24-72 hours, 24-36 hours, 36-96 hours, 36-72 hours, 48-96 hours, 48-72 hours, 60-96 hours, 48-60 hours or 60-72 hours), (f) after the incubation period, separating control plasma or supernatant from the control whole blood sample, and (g) assessing citrullination of a citrullination site on a protein or peptide fragment thereof that is present in the control plasma or supernatant. In some cases, an outcome of the assessing in step (g) is compared with an outcome of the assessing in step (d). The disclosure herein also encompasses, for example, an in vitro method of assessing PAD4-dependent citrullination, the method comprising assessing citrullination of a citrullination site on a protein or peptide fragment thereof that is present in plasma or supernatant that has been separated from a whole blood sample that has been incubated at 34-40°C for an incubation period (such as at a temperature of 36 to 39°C, at a temperature of 36 to 38°C, or at a temperature of 37°C for at least 12 hours, at least 18 hours, 12-96 hours, 24-96 hours, 24-72 hours, 24-36 hours, 36-96 hours, 36-72 hours, 48-96 hours, 48-72 hours, 60-96 hours, 48-60 hours or 60-72 hours). In any of these methods herein, the sample can be a plasma or supernatant from a whole blood sample. In some cases the plasma or supernatant sample has not been frozen before assessment, while in other cases the sample has been frozen and thawed, and in some instances the method further comprises freezing and thawing the plasma or supernatant after separation from whole blood but prior to the assessing.In some cases, a sample may be contacted with a reagent, such as an affinity reagent, to enrich or purify a protein or a peptide fragment thereof harboring a citrullination site to be analyzed. For example, in some cases the method comprises “immunoenriching” a sample for a protein or a peptide fragment thereof that is of interest, the protein or peptide harboring a citrullination site for assessment. Such “immunoenriching” may comprise contacting the sample with an antibody reagent that specifically binds to the protein and / or to a peptide fragment thereof (e.g., comprising an epitope of the protein of interest) that contains a citrullination site. In some cases, the antibody reagent binds to the protein or peptide in both the non-citrullinated and citrullinated forms. Accordingly, the protein or peptide fragment thereof may be enriched prior to assessment of citrullination. In some cases, an antibody or other affinity reagent may be immobilized, such as by attachment to a solid surface, such as a bead, chip, plate or well of a plate. Such immobilization, for instance, may assist in separating a protein of interest for assessment of citrullination from other proteins in the sample. In some cases, the reagent used for immunoenriching is an antibody attached to a solid surface, such as a bead, such as a magnetic bead, or a chip, plate, or well of a plate. In some such cases, the sample may be a sample that comprises or is whole blood, serum, plasma, synovial fluid, pleural fluid, interstitial fluid, sputum, urine, or another biological sample.Accordingly, methods of the disclosure herein also include, for example, a method comprising: (a) immunoenriching a sample for a protein of interest or a peptide fragment thereof to form an immunoenriched sample, wherein the immunoenriching comprises contacting the serum or plasma sample with an antibody that specifically binds to both citrullinated and noncitrullinated forms of the protein of interest or protein fragment thereof, the protein of interest or peptide comprising a citrullination site, and (b) assessing citrullination in the immunoenriched sample at the citrullination site. In some cases, a method disclosed herein comprises: (a) immunoenriching a sample for a protein of interest to form an immunoenriched sample, wherein the immunoenriching comprises contacting the serum or plasma sample with an antibody that binds to both citrullinated and noncitrullinated forms of the protein of interest or peptide fragment thereof, the protein of interest or peptide fragment thereof comprising a citrullination site, (b) enzymatically digesting the immunoenriched sample to form digested peptides from the protein of interest, wherein steps (a) and (b) can be in any order, and (c) assessing citrullination of the digested peptides at the citrullination site. In other cases, the method comprises (a) immunoenriching a sample bycontacting the sample with an immobilized antibody that binds to both citrullinated and noncitrullinated forms of a protein of interest, the protein of interest comprising a citrullination site, (b) eluting protein bound to the immobilized antibody, (d) enzymatically digesting the eluted protein to form digested peptides, and (e) assessing citrullination of the digested peptides at the citrullination site. In any of the above methods, the sample may be diluted prior to the immunoenriching step, such as by 2-1000 fold. In any of the above methods, the sample may be a whole blood, plasma, serum, or synovial fluid sample. In some embodiments, it is a plasma or serum sample. In some cases, the immunoenrichment is conducted prior to enzymatic digestion of the protein of interest. In other cases, the protein of interest is first enzymatically digested, and then one or more peptide fragments thereof are immunoenriched. In some cases, the sample may be diluted to a volume of at least 5 pl, e.g., to a volume of 5 pl- 1 OOpl, 5 pl-50pl, 5 pl-25 pl, 5 pl- 15 pl, e.g., to a volume of lOpl. In any of the above methods, the immunoenriching may comprise incubating the sample with the immobilized antibody for at least 30 minutes, such as for a period of 30-90 minutes. In some cases, the incubation is for 30-60 minutes, 40-80 minutes, 50 to 70 minutes, 55 to 65 minutes, or for 60 minutes. The incubating may be at a temperature of 22-28°C, or may be at room temperature. In some cases, the immunoenriching comprises shaking during the incubating (e.g., at 800-1200 rpm or at 1000 rpm). In some cases, the immunoenriching comprises removing the immobilized antibody from the sample and washing the immobilized antibody prior to the eluting, for example with a wash buffer, e.g., a wash buffer comprising PBS (phosphate buffered saline). In some cases, the eluting comprises washing the immobilized antibody with an elution composition. A variety of elution compositions may be used, including, for example elution compositions that elute a protein of interest based on a change of pH, such as elution compositions that are acidic, and / or that comprise a detergent such as a zwitterionic detergent. In some cases, the elution buffer may comprise an acidic solution, optionally further comprising a buffer or ion, such as a zwitterion. In some cases, the buffer is exchanged prior to assessing citrullination, and optionally prior to intermediate steps such as enzymatic digestion, if such steps are performed. For example, if an acidic elution composition is used, then the buffer may be altered to a neutral pH range for subsequent steps, for example. In some cases, proteins that have been immunoenriched according to methods herein are denatured and / or enzymatically digested prior to assessment of citrullination. For example, proteins may be denatured to remove tertiary structure, for example, by incubation at above physiological temperatures, such as at 60-90°C, such as 60-80°C, 70-85°C, or 80°C, for a period of 5-30 minutes, such as 10-30, 10-20, 15-25, or 20 minutes. In other cases, a chemical denaturant such as urea could be applied. A proteolytic enzyme such as trypsin, LysC, rLysC, LysN, GluC, AspN, rAspN, or a combination of proteolytic enzymes, such as more than one of trypsin, LysC, rLysC, LysN, GluC, AspN, and rAspN, could be used for enzymatic digestion.In these above methods, the protein of interest may comprise any of the proteins listed herein, such as those listed in Table A above, and the citrullination site to be assessed may comprise any one or more of those listed in Table A or in Tables 3-18, herein, for example. In some cases, the protein of interest comprises fibrinogen alpha chain and / or gelsolin. In such cases, the citrullination site for assessment may comprise the fibrinogen citrullination site located at R591 of P02671, which in some cases may be assessed via a peptide of sequence QFTSSTSYNRGDSTFESK (SEQ ID NO: 249), wherein the R is the citrullination site. In such cases, the citrullination site for assessment may comprise the gelsolin citrullination site located at R32 of P06396, which in some cases may be assessed via a peptide of sequence ATASRGASQAGAPQGR (SEQ ID NO: 255), wherein the underlined R is the citrullination site. An exemplary antibody that could be used to immunoenrich fibrinogen, for example, may be a recombinant anti-fibrinogen antibody, such as Abeam antibody 244646. An exemplary antibody that could be used to immunoenrich gelsolin, for example, may be a recombinant anti-gelsolin antibody such as antibody 247406. In some such embodiments, immunoenrichment of the sample is conducted prior to enzymatic digestion.In any of the methods above comprising immunoenrichment and enzymatic digestion, assessment of citrullination may be conducted by mass spectroscopy (MS), for example, by liquid chromatography followed by mass spectroscopy such as tandem mass spectroscopy (LC-MS or LC-MS / MS).The above methods may be used in a wide variety of contexts, and with a wide range of PAD4 modulators, such as PAD4 inhibitors and PAD4 agonists, and with other therapeutic agents such as those used for treatment of citrullination-related diseases, as well as those that target biological pathways that involve PAD4, such as NETosis and / or METosis, and those that otherwise can impact citrullination activity by PAD4 or PAD4 expression. For example, they may be used for testing new PAD4 modulators or other agents to determine their effect on citrullination of certain sites. Or they may be used to check the activity of known PAD4 modulators or other agents. Or they may be used to monitor the effect of PAD4 modulatorsor other therapeutic agents, for example, on citrullination levels, after administration to a patient. Thus, in some cases, a biological sample may be used for testing the effect of a PAD4 modulator or other therapeutic agent that has not been administered to a subject, and the PAD4 modulator or other therapeutic agent may be exposed to the biological sample by incubating the sample with the modulator. In other cases, the biological sample may be taken from a subject who has been previously administered the PAD4 modulator or other therapeutic agent, and thus the sample may have been exposed to the PAD4 modulator through administration of the PAD4 modulator or other therapeutic agent to the subject from whom the sample is obtained. In some cases, the PAD4 modulator or other therapeutic agent is an anti -histone antibody, such as CIT-013. In some such cases, the PAD4 modulator or other therapeutic agent is a PAD4 modulator. In some cases, it is a PAD4 inhibitor, such as an anti-PAD4 antibody or small molecule PAD4 inhibitor. In some cases, a PAD4 modulator does not significantly affect the activity of any protein species other than PAD4. In some such cases, the PAD4 modulator does not significantly affect the activity of PAD2, for example. In other cases, the PAD4 modulator modulates the activity of PAD4 as well as at least one other protein, such as PAD2. Certain exemplary PAD4 modulators compatible with methods herein are described below.PAD4 modulators may be administered, for example, to subjects who have a citrullination-related disease such as an autoimmune disease or infectious disease or cancer, for example, or who are at risk for developing such a disease. Such diseases and related subjects are discussed in more detail in following sections herein. In some cases, the subject has been diagnosed with an autoimmune disorder or is at risk for developing an autoimmune disorder. In some cases, the citrullination-related disease is the citrullination-related disease is rheumatoid arthritis, lupus (e.g., systemic lupus erythematosus (SLE)), lupus nephritis, vasculitis (e.g., ANCA-associated vasculitis), thrombosis (e.g, venous thrombosis), or inflammatory bowel disease (IBD) (e.g., ulcerative colitis, Crohn’s disease). In some cases the subject has been diagnosed with rheumatoid arthritis (RA) or is at risk for developing rheumatoid arthritis. In other cases, however, the subject has not been diagnosed with an autoimmune disease such as RA, or the subject is not at considered to be at risk of developing such a disease. Thus, in some cases, is a normal, healthy subject. In some cases, the subject is positive for anti-citrullinated protein antibodies (ACPA positive). In some cases, the subject is positive for anti-PAD4 activating antibodies. In cases where a subject is ACPApositive or positive for anti-PAD4 activating antibodies, the subject may also be considered at risk for developing an autoimmune disorder such as RA.Methods may also be used, for example, to assess citrullination levels in subjects not currently on therapeutic treatment, or who are not receiving a PAD4 modulator. Thus, in some cases, is a normal, healthy subject. In some cases, the subject is positive for anti- citrullinated protein antibodies (ACPA positive). In some cases, the subject is considered at risk for developing an autoimmune disorder or citrullination-related disease.Methods as described herein may also be performed, for example, to assess citrullination of sites in laboratory animals such as mice, citrullinated by murine PAD4, for instance, by assessing citrullination of murine citrullination sites and related peptides such as to test murine PAD4 modulators and inhibitors. See for example international Patent Publication No. W02024 / 020579, describing exemplary murine PAD4 antibodies.III. Exemplary PAD4 ModulatorsExemplary Small Molecule PAD4 ModulatorsExamples of PAD4 modulators include various small molecule compounds that may increase or reduce PAD4 activity, such as citrullination of amino acid residues. Examples of small molecule PAD4 modulators include benzimidazole-derived compounds and heteroaryl compounds, as well as peptides, such as peptide macrocycles. Exemplary small molecule PAD4 modulators, for example, include compounds disclosed in International Patent Publication No. W02014 / 015905, which describes benzimidazole-derived PAD4 modulators such as PAD4 inhibitors, for instance 2-(azaindole-2-yl)benzimidazoles. Additional small molecule PAD4 modulators such as PAD4 inhibitors, are also described in International Patent Publication Nos. WO2016 / 185279, WO2017 / 007405, WO2017 / 100601, WO20 17 / 100594, W02017 / 147102, WO2018 / 022897, WO2018 / 049296, WO2019 / 058393, W02020 / 033490, W02020 / 033514, W02020 / 033520, W02020 / 033488, WO2021 / 158840, WO2021 / 163254, WO2022 / 173722, WO2022 / 140428, WO2022 / 221642, and WO2023 / 083365, for example. Others include compounds disclosed in United States Patent application or publication numbers US11198681, US20220402950, US11524959, US20230203039, US20220348562, US11878965, US20220227787, US11976083. Others include, for example, GSK121, GSK199, AFM-30a, and GSK 484, described in Lewis et al. (2015) Nat Chem Biol 11(3): 189-191 and Chen et al., doi 10.1136 / annrheumdis-2023- eular.2894 (2023; BMS-P5, described in Li et al. (2020) Mol Cancer Ther 19(7): 1530-1538;JBI-589, described in Deng et al. (2022) Cancer Res 82(19): 3561-3572; JBI-1044, described in US20200237771, and US2020276206; YW3-56, described in Wang et al. (2012) J Biol Chem 287(31): 25941-25953; ZD-E-1M, described in Zhu et al. (2022) Acta Pharm Sin B 12(5): 2592-2608; modified and unmodified Streptonigrin described in Dreyton et al. (2012) Probe Reports from the NIH Molecular Libraries Program and Dreyton et al. (2014) Bioorg and Med Chem 22(4): 1362-9; Cl-amidine, described in Luo et al. (2006) Biochemistry 45(39): 11727-11736, and its modifications including BB-Cl-amidine (Knight et al (2015) Ann Rhuem Dis , 74(12): 2199-2206), and o-Cl-amidine (Causey et al. (2011) J. Med Chem 54(19): 6919-6935); F-amidine, Luo et al. (2006) J Am Chem Soc 128(4): 1092-1093, and its modifications including BB-F-amidine (Muth et al. (2017) J Med Chem 60(7): 3198-3211), and o-F-amidine (Causey et al. (2011) J. Med Chem 54(19): 6919-6935); TDFA, described in Jones et al. (2012) ACS Chem Biol 7(1): 160-165; SC97362 and others, described in Aliko et al. (2019) Int J Mol Sci 20(9): 2174; NSC95397, ruthenium red, and sanguinarine, described in Lewallen et al. (2014) ACS Chem Biol 9(4): 913-921; chlorotetracycline, minocycline, and streptomycin, described in Knuckley et al. (2007) Bioorg Med Chem 16(2): 739-745; and Lucid-21-302, described in WO-2017 / 027967. Other examples include the inhibitors described in WO2017 / 027967; WO2014 / 019092; Zhu et al. (2023) Eur J Med Chem 258: 115619; Zhu et al. (2024) J Med Chem 67(10):7973-7994; Jia et al. (2023) Biomed Pharmacother 168:115826; Muth et al. (2017) J Med Chem 60(7): 3198-3211; Sarswat et al. (2017) Bioorg Med Chem 25(9):2643-2656; Wei et al. (2014) J Med Chem 56(4) 1715-1722; Teo et al. (2017) Chem Biol Drug Des 90(6): 1134-1146; Nadzirin (2021) Comput Biol Chem 92: 107487; and Mondal et al. (2019) Acc Chem Res 52(3): 818-832.In other cases, antibodies may be used as PAD4 modulators. Examples of such antibodies include those described in WO2016 / 143753, US2018 / 0044434, WO2019 / 131769, WO2022 / 176970, Zhou et al. (2024) Nat Chem Biol 20:742-750, and Wang et al. (2022) Biomedicine and Pharmacotherapy 153: 113289. Additionally, Sims et al, doi 10.1136 / annrheumdis-2024-eular.3510 (2024) and Chen et al., doi 10.1136 / annrheumdis- 2023-eular.2894 (2023) describe PAD2 / PAD4 bispecific antibodies, and WO2016 / 155745 describes a cross-reactive antibody capable of binding both PAD2 and PAD4. Further examples of anti-PAD4 antibodies are described in this section and the sections that follow, and further in W02024 / 020579, and the amino acid sequences of the antibodies described below are also provided herein.Each of the above-referenced publications is incorporated herein by reference in its entirety.Clone 13 and Related Anti-PAD4 AntibodiesOne group of exemplary anti-PAD4 antibodies is based on a murine anti-human antibody called “clone 13,” which was prepared in its original murine anti-human form, and was then humanized to create a series of antibodies called hzl3-l to hzl3-12, of which hzl3- 5 and hzl3-12 were further modified at position D31 to D3 IE (antibodies hzl3-5 D3 IE and hzl3-12 D3 IE) . A cryo EM study of a clone 13 Fab binding to PAD4 and paratope mapping to identify the portions of the clone 13 variable regions and its humanized variants that directly contact PAD4 provided further structural information as to the parts of clone 13 variable regions and those of its related humanized antibodies that dictate PAD4 binding. Antibody hzl3-5 was also further modified to identify antibodies with pH dependent binding to PAD4. The clone 13 antibody and its humanized derivatives are described in International Patent Publication W02024 / 020579, as well as in the instant priority application, US Provisional Appl. No. 63 / 528,323, filed July 21, 2023, the contents of both being incorporated herein by reference.For example, in some embodiments, a PAD4 modulator or PAD4 inhibitor comprises an anti-PAD4 antibody that specifically binds to protein arginine deiminase 4 (PAD4) and comprises a heavy chain variable region (VH) comprising a heavy chain complementarity determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO: 4, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 5, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 6; and a light chain variable region (VL) comprising a light chain complementarity determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO: 7, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 8, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 9.In some embodiments, the antibody specifically binds to protein arginine deiminase 4 (PAD4) and comprises a heavy chain variable region (VH) comprising a heavy chain complementarity determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO: 62, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 5, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 6; and a light chain variable region (VL) comprising a light chain complementarity determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO: 7, an LCDR2 comprising the amino acidsequence of SEQ ID NO: 8, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 9.In some embodiments, the antibody comprises a heavy chain variable region (VH) comprising a heavy chain complementarity determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO: 4 or 62 and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 6; and a light chain variable region (VL) comprising a light chain complementarity determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO: 7. In particular, paratope mapping and structural analysis of antibodies comprising the above sets of heavy and light chain CDRs revealed that it is the HCDR1, HCDR3, and LCDR1 that make contact with PAD4. (See Figs. 8A-8B.) Hence, in some embodiments, antibodies herein comprise the above set of these three CDRs. In some embodiments, the antibodies comprise a VH comprising a HCDR1 comprising the amino acid sequence of SEQ ID NO: 4 and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 6; and a VL comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO: 7. In other embodiments, the antibodies comprise a VH comprising a HCDR1 comprising the amino acid sequence of SEQ ID NO: 62 and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 6; and a VL comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO: 7.In some embodiments, the antibody comprises a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 221 or 225 and the amino acid sequence of SEQ ID NO: 222; and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 223. Each of these paratope regions was identified as contacting PAD4, as described in priority application No. 63 / 528,323 and international Patent Publication No. W02024 / 020579. In some embodiments, the antibody further comprises a light chain constant region comprising the amino acid sequence of SEQ ID NO: 224.In some embodiments, the antibody comprises a VH comprising a glycine at Kabat position 94 (Gly94). Thus, for example, the originally identified mouse anti-human clone 13 antibody comprises a glycine at Kabat position 94, but several human framework regions do not. Thus, in certain humanized antibodies, a back mutation is necessary to obtain a glycine at Kabat position 94. Gly94 is an amino acid residue in the loop adjacent to the VH CDR3 (i.e., the VH CDR3 loop). In some embodiments, Gly94 is implicated in the flexibility and / or the geometry of the VH CDR3 loop. In some embodiments, Gly94 may interact with VH CDR3. In some embodiments, Gly94 is implicated in the activity of the anti-PAD4 antibody. In someembodiments, mutation of Gly94 to a different amino acid, such as a threonine, results in a decrease in flexibility in the VH CDR3 loop, a change in geometry in the VH CDR3 loop, a decrease in interaction between the amino acid at position 94 and the VH CDR3 loop, a decrease in binding of the anti-PAD4 antibody to PAD4, a decrease in activity of the anti- PAD4 antibody, an increase in binding of the anti-PAD4 antibody to extracellular matrix (ECM) proteins, a change in anti-PAD4 antibody secondary structure, a decrease in the stability of the anti-PAD4 antibody, or any combination thereof. Accordingly, in some embodiments, the VH of the antibody comprises a glycine at Kabat position 94 (position 98 of SEQ ID NO: 10). (See Fig. IE of priority application No. 63 / 528,323 and International Patent Publication No. W02024 / 020579).In some embodiments, the antibody comprises a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of any one of SEQ ID NOs: 10, 14, 18, 22, 26, 30, 34, 38, 42, 46, 50, 54, 58, or 68. In some embodiments, the antibody comprises a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of any one of SEQ ID NOs: 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, or 70. In some embodiments, the antibody comprises both a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of any one of SEQ ID NOs: 10, 14, 18, 22, 26, 30, 34, 38, 42, 46, 50, 54, 58, or 68; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of any one of SEQ ID NOs: 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, or 70. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of any one of SEQ ID Nos: 10, 14, 18, 22, 26, 30, 34, 38, 42, 46, 50, 54, 58, or 68 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of any one of SEQ ID Nos: 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, or 70 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises a both a VH comprising the amino acid sequence of any one of SEQ ID Nos: 10, 14, 18, 22, 26, 30, 34, 38, 42, 46, 50, 54, 58, or 68 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions and a VL comprising the amino acid sequence of any one of SEQ ID Nos: 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, or 70 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some such cases, the antibody VH and VL further comprise (a) an HCDR1 comprising the amino acid sequence ofSEQ ID NO: 4 or 62 and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 6 and an LCDR1 comprising the amino acid sequence of SEQ ID NO: 7, (b) an HCDR1 comprising the amino acid sequence of SEQ ID NO: 4 or 62, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 5, an HCDR3 comprising the amino acid sequence of SEQ ID NO: 6, an LCDR1 comprising the amino acid sequence of SEQ ID NO: 7, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 8 an LCDR3 comprising the amino acid sequence of SEQ ID NO: 9, or (c) the amino acid sequence of SEQ ID NO: 221 or 225 in the VH and the amino acid sequence of SEQ ID NO: 222 in the VL, further optionally with a light chain constant region comprising the amino acid sequence of SEQ ID NO: 224. Thus, in such cases, the variation in the VH and VL compared to the above listed sequence identification numbers is located in regions outside of these specific CDR or paratope sequences. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of any one of SEQ ID Nos: 10, 14, 18, 22, 26, 30, 34, 38, 42, 46, 50, 54, 58, or 68. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of any one of SEQ ID Nos: 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, or 70.In yet further embodiments, the antibody comprises both a VH comprising the amino acid sequence of any one of SEQ ID Nos: 10, 14, 18, 22, 26, 30, 34, 38, 42, 46, 50, 54, 58, or 68; and a VL comprising the amino acid sequence of any one of SEQ ID Nos: 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, or 70. Thus, for example, the following exemplary antibodies are within the scope of this disclosure:An isolated antibody that specifically binds to protein arginine deiminase 4 (PAD4), wherein the antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 10 and a VL comprising the amino acid sequence of SEQ ID NO: 12;An isolated antibody that specifically binds to protein arginine deiminase 4 (PAD4), wherein the antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 14 and a VL comprising the amino acid sequence of SEQ ID NO: 16;An isolated antibody that specifically binds to protein arginine deiminase 4 (PAD4), wherein the antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 18 and a VL comprising the amino acid sequence of SEQ ID NO: 20;An isolated antibody that specifically binds to protein arginine deiminase 4 (PAD4), wherein the antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 22 and a VL comprising the amino acid sequence of SEQ ID NO: 24;An isolated antibody that specifically binds to protein arginine deiminase 4 (PAD4), wherein the antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 26 and a VL comprising the amino acid sequence of SEQ ID NO: 28;An isolated antibody that specifically binds to protein arginine deiminase 4 (PAD4), wherein the antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 30 and a VL comprising the amino acid sequence of SEQ ID NO: 32;An isolated antibody that specifically binds to protein arginine deiminase 4 (PAD4), wherein the antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 34 and a VL comprising the amino acid sequence of SEQ ID NO: 36;An isolated antibody that specifically binds to protein arginine deiminase 4 (PAD4), wherein the antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 38 and a VL comprising the amino acid sequence of SEQ ID NO: 40;An isolated antibody that specifically binds to protein arginine deiminase 4 (PAD4), wherein the antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 42 and a VL comprising the amino acid sequence of SEQ ID NO: 44;An isolated antibody that specifically binds to protein arginine deiminase 4 (PAD4), wherein the antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 46 and a VL comprising the amino acid sequence of SEQ ID NO: 48;An isolated antibody that specifically binds to protein arginine deiminase 4 (PAD4), wherein the antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 50 and a VL comprising the amino acid sequence of SEQ ID NO: 52;An isolated antibody that specifically binds to protein arginine deiminase 4 (PAD4), wherein the antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 54 and a VL comprising the amino acid sequence of SEQ ID NO: 56;An isolated antibody that specifically binds to protein arginine deiminase 4 (PAD4), wherein the antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 58 and a VL comprising the amino acid sequence of SEQ ID NO: 60;An isolated antibody that specifically binds to protein arginine deiminase 4 (PAD4), wherein the antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 68 and a VL comprising the amino acid sequence of SEQ ID NO: 70.In any of the above antibodies, in some cases the antibody binds to an epitope on PAD4 comprising SEQ ID NO: 217 and SEQ ID NO: 218.In some embodiments herein, the anti-PAD4 antibody is an IgA, IgG, or IgM antibody. In some cases, the antibody is an IgG antibody, such as a human IgGl, IgG2, IgG3, or IgG4 antibody or a murine IgGl or IgG2 antibody. In some cases, the antibody comprises a wild-type, human IgGl, IgG2, or IgG4 heavy chain constant region. In some embodiments, the antibody comprises a full length heavy chain and / or a full length light chain. In other cases, the antibody lacks a C-terminal lysine at the end of the heavy chain constant region. In yet other cases, the antibody lacks a C-terminal glycine-lysine at the end of the heavy chain constant region. In some cases, the antibody is an antibody fragment, such as an Fv, singlechain Fv (scFv), Fab, Fab’, or (Fab’)2.In some embodiments, the anti-PAD4 antibody is a bispecific or multispecific antibody, or which is conjugated covalently or noncovalently to at least one other molecule. In some embodiments, the antibody is conjugated covalently or noncovalently to at least one other molecule, wherein the at least one other molecule comprises a detection label and / or a drug.In some embodiments, the antibody comprises a human IgGl heavy chain constant region comprising an amino acid sequence at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of any one of SEQ ID Nos: 174, 176, 178, 180, 182, 184, 186, 188, 190, or 192. In some embodiments, the antibody comprises a light chain constant region comprising an amino acid sequence at least 90%, at least 95%, at least 97%,or at least 99% identical to the amino acid sequence of SEQ ID NO: 194. In some embodiments, the antibody comprises both a human IgGl heavy chain constant region comprising an amino acid sequence at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of any one of SEQ ID Nos: 174, 176, 178, 180, 182, 184, 186, 188, 190, or 192; and a light chain constant region comprising an amino acid sequence at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 194. In some cases, the antibody comprises a heavy chain constant region comprising an amino acid sequence modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions compared to the amino acid sequence of any one of SEQ ID Nos: 174, 176, 178, 180, 182, 184, 186, 188, 190, or 192. In some cases, the antibody comprises a light chain constant region comprising an amino acid sequence modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions compared to the amino acid sequence of SEQ ID NO: 194. In some cases, the antibody comprises both a heavy chain constant region comprising an amino acid sequence modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions compared to the amino acid sequence of any one of SEQ ID Nos: 174, 176, 178, 180, 182, 184, 186, 188, 190, or 192; and a light chain constant region comprising an amino acid sequence modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions compared to the amino acid sequence of SEQ ID NO: 194. In some embodiments, the antibody comprises a human IgGl heavy chain constant region comprising amino acid sequence of any one of SEQ ID Nos: 174, 176, 178, 180, 182, 184, 186, 188, 190, or 192. In some embodiments, the antibody comprises a light chain constant region comprising the amino acid sequence of SEQ ID NO: 194. In some embodiments, the antibody comprises both a human IgGl heavy chain constant region comprising the amino acid sequence of any one of SEQ ID Nos: 174, 176, 178, 180, 182, 184, 186, 188, 190, or 192; and a light chain constant region comprising the amino acid sequence of SEQ ID NO: 194.Clone 20 and Related AntibodiesThe methods herein may also be conducted with anti-PAD4 antibodies derived from a second mouse anti -human antibody, clone 20, and its humanized variants hz20-l to hz20-14, as also described in International Patent Publication W02024 / 020579, as well as in the instant priority application, US Provisional Appl. No. 63 / 528,323, filed July 21, 2023, the contents of both being incorporated herein by reference. Accordingly, in some embodiments,an anti-PAD4 antibody comprises an isolated antibody that specifically binds to protein arginine deiminase 4 (PAD4), wherein the antibody comprises a heavy chain variable region (VH) comprising a heavy chain complementarity determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO: 72, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 73, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 74; and a light chain variable region (VL) comprising a light chain complementarity determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO: 75, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 76, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 77.In some embodiments, the antibody comprises a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of any one of SEQ ID NOs: 78, 82, 86, 90, 94, 98, 102, 106, 110, 114, 118, 122, 126, 130, or 134. In some embodiments, the antibody comprises a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of any one of SEQ ID NOs: 80, 84, 88, 92, 96, 100, 104, 108, 112, 116, 120, 124, 128, 132, or 136. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of any one of SEQ ID Nos: 78, 82, 86, 90, 94, 98, 102, 106, 110, 114, 118, 122, 126, 130, or 134 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions; and wherein the antibody comprises a VL comprising the amino acid sequence of any one of SEQ ID Nos: 80, 84, 88, 92, 96, 100, 104, 108, 112, 116, 120, 124, 128, 132, or 136 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some such cases, the antibody VH further comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO: 72, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 73, or an HCDR3 comprising the amino acid sequence of SEQ ID NO: 74. In some cases, the antibody VL further comprises an LCDR1 comprising the amino acid sequence of SEQ ID NO: 75, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 76, or an LCDR3 comprising the amino acid sequence of SEQ ID NO: 77. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of any one of SEQ ID Nos: 78, 82, 86, 90, 94, 98, 102, 106, 110, 114, 118, 122, 126, 130, or 134. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of any one of SEQ ID Nos: 80, 84, 88, 92, 96, 100, 104, 108, 112, 116, 120, 124, 128, 132, or 136.In yet further embodiments, the antibody comprises a VH comprising the amino acid sequence of any one of SEQ ID Nos: 78, 82, 86, 90, 94, 98, 102, 106, 110, 114, 118, 122,126, 130, or 134; and comprises a VL comprising the amino acid sequence of any one of SEQ ID Nos: 80, 84, 88, 92, 96, 100, 104, 108, 112, 116, 120, 124, 128, 132, or 136. Thus, for example, the following exemplary antibodies are within the scope of this disclosure:An isolated antibody that specifically binds to protein arginine deiminase 4 (PAD4), wherein the antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 78 and a VL comprising the amino acid sequence of SEQ ID NO: 80;An isolated antibody that specifically binds to protein arginine deiminase 4 (PAD4), wherein the antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 82 and a VL comprising the amino acid sequence of SEQ ID NO: 84;An isolated antibody that specifically binds to protein arginine deiminase 4 (PAD4), wherein the antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 86 and a VL comprising the amino acid sequence of SEQ ID NO: 88;An isolated antibody that specifically binds to protein arginine deiminase 4 (PAD4), wherein the antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 90 and a VL comprising the amino acid sequence of SEQ ID NO: 92;An isolated antibody that specifically binds to protein arginine deiminase 4 (PAD4), wherein the antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 94 and a VL comprising the amino acid sequence of SEQ ID NO: 96;An isolated antibody that specifically binds to protein arginine deiminase 4 (PAD4), wherein the antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 98 and a VL comprising the amino acid sequence of SEQ ID NO: 100;An isolated antibody that specifically binds to protein arginine deiminase 4 (PAD4), wherein the antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 102 and a VL comprising the amino acid sequence of SEQ ID NO: 104;An isolated antibody that specifically binds to protein arginine deiminase 4 (PAD4), wherein the antibody comprises a VH comprising the amino acidsequence of SEQ ID NO: 106 and a VL comprising the amino acid sequence of SEQ ID NO: 108;An isolated antibody that specifically binds to protein arginine deiminase 4 (PAD4), wherein the antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 110 and a VL comprising the amino acid sequence of SEQ ID NO: 112;An isolated antibody that specifically binds to protein arginine deiminase 4 (PAD4), wherein the antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 114 and a VL comprising the amino acid sequence of SEQ ID NO: 116;An isolated antibody that specifically binds to protein arginine deiminase 4 (PAD4), wherein the antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 118 and a VL comprising the amino acid sequence of SEQ ID NO: 120;An isolated antibody that specifically binds to protein arginine deiminase 4 (PAD4), wherein the antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 122 and a VL comprising the amino acid sequence of SEQ ID NO: 124;An isolated antibody that specifically binds to protein arginine deiminase 4 (PAD4), wherein the antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 126 and a VL comprising the amino acid sequence of SEQ ID NO: 128;An isolated antibody that specifically binds to protein arginine deiminase 4 (PAD4), wherein the antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 130 and a VL comprising the amino acid sequence of SEQ ID NO: 132;An isolated antibody that specifically binds to protein arginine deiminase 4 (PAD4), wherein the antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 134 and a VL comprising the amino acid sequence of SEQ ID NO: 136.In any of the above antibodies, in some cases, the antibody binds to an epitope on PAD4 comprising SEQ ID NO: 219 and SEQ ID NO: 220.In some embodiments herein, the antibody is an IgA, IgG, or IgM antibody. In some cases, the antibody is an IgG antibody, such as a human IgGl, IgG2, IgG3, or IgG4 antibody or a murine IgGl or IgG2 antibody. In some cases, the antibody comprises a wild-type, human IgGl, IgG2, or IgG4 heavy chain constant region. In certain aspects, the antibody is of the human IgGl isotype. In certain aspects, the antibody is of the human IgGl isotype with a P329G, L234A and L235A (LALAPG; EU numbering) mutation to reduce Fc-region effector function. In other aspects, the antibody is of the human IgG2 isotype. In certain aspects, the antibody is of the IgG4 isotype with an S228P mutation (EU numbering) in the hinge region to improve stability of IgG4 antibody. In some aspects, the antibody (e.g., a non-humanized antibody) may have a non-human IgG constant region, and may be, for example, a murine IgG2a antibody such as a murine IgG2a LALAPG antibody. In some embodiments, the antibody comprises a full length heavy chain and / or a full length light chain. In other cases, the antibody lacks a C-terminal lysine at the end of the heavy chain constant region. In yet other cases, the antibody lacks a C-terminal glycine-lysine at the end of the heavy chain constant region. In some cases, the antibody is an antibody fragment, such as an Fv, singlechain Fv (scFv), Fab, Fab’, or (Fab’)2.In some embodiments, the antibody is a bispecific or multispecific antibody, or which is conjugated covalently or noncovalently to at least one other molecule. In some embodiments, the antibody is conjugated covalently or noncovalently to at least one other molecule, wherein the at least one other molecule comprises a detection label and / or a drug.In some embodiments, the antibody comprises a human IgGl heavy chain constant region comprising an amino acid sequence at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of any one of SEQ ID Nos: 174, 176, 178, 180, 182, 184, 186, 188, 190, or 192. In some embodiments, the antibody comprises a light chain constant region comprising an amino acid sequence at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 194. In some embodiments, the antibody comprises both a human IgGl heavy chain constant region comprising an amino acid sequence at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of any one of SEQ ID Nos: 174, 176, 178, 180, 182, 184, 186, 188, 190, or 192; and a light chain constant region comprising an amino acid sequence at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 194. In some cases, the antibody comprises a heavy chain constant region comprising an amino acid sequence modified by 1-10 amino acid substitutions, 1-5amino acid substitutions, or 1-3 amino acid substitutions compared to the amino acid sequence of any one of SEQ ID Nos: 174, 176, 178, 180, 182, 184, 186, 188, 190, or 192. In some cases, the antibody comprises a light chain constant region comprising an amino acid sequence modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions compared to the amino acid sequence of SEQ ID NO: 194. In some cases, the antibody comprises both a heavy chain constant region comprising an amino acid sequence modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions compared to the amino acid sequence of any one of SEQ ID Nos: 174, 176, 178, 180, 182, 184, 186, 188, 190, or 192; and a light chain constant region comprising an amino acid sequence modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions compared to the amino acid sequence of SEQ ID NO: 194. In some embodiments, the antibody comprises a human IgGl heavy chain constant region comprising amino acid sequence of any one of SEQ ID Nos: 174, 176, 178, 180, 182, 184, 186, 188, 190, or 192. In some embodiments, the antibody comprises a light chain constant region comprising the amino acid sequence of SEQ ID NO: 194. In some embodiments, the antibody comprises both a human IgGl heavy chain constant region comprising the amino acid sequence of any one of SEQ ID Nos: 174, 176, 178, 180, 182, 184, 186, 188, 190, or 192; and a light chain constant region comprising the amino acid sequence of SEQ ID NO: 194. pH Dependent Clone 13 -Related AntibodiesFurther examples of anti-PAD4 antibodies to which methods herein apply include variants of parental antibody clone 13 or hzl3-5, such as to impact the pH dependence of PAD4 binding. These are also described in International Patent Publication W02024 / 020579, as well as in the instant priority application, US Provisional Appl. No. 63 / 528,323, filed July 21, 2023, the contents of both being incorporated herein by referenceIn some such embodiments, the antibody comprises a VH comprising an HCDR1 comprising the amino acid sequence of positions 26-35, an HCDR2 comprising the amino acid sequence of positions 50-66, and an HCDR3 comprising the amino acid sequence of positions 99-108 of SEQ ID NO: 138, SEQ ID NO: 140, SEQ ID NO: 142, SEQ ID NO: 144, SEQ ID NO: 146, SEQ ID NO: 148, SEQ ID NO: 150, SEQ ID NO: 152, SEQ ID NO: 154, SEQ ID NO: 156, SEQ ID NO: 158, SEQ ID NO: 160, SEQ ID NO: 162, SEQ ID NO: 164, SEQ ID NO: 166, or SEQ ID NO: 168. In some embodiments above, the antibody further comprises a VL comprising an LCDR1 comprising the amino acid sequence of residues 24-38 of SEQ ID NO: 170, an LCDR2 comprising the amino acid sequence of residues 54-60 of SEQ ID NO: 170, and an LCDR3 comprising the amino acid sequence of residues 93-101 of SEQ ID NO: 170. In other embodiments above, the antibody further comprises a VL comprising an LCDR1 comprising the amino acid sequence of residues 24-38 of SEQ ID NO: 172, an LCDR2 comprising the amino acid sequence of residues 54-60 of SEQ ID NO: 172, and an LCDR3 comprising the amino acid sequence of residues 93-101 of SEQ ID NO: 172.In some embodiments, the antibody comprises:- a VH comprising an HCDR1 comprising the amino acid sequence of positions 26-35 of SEQ ID NO: 138, an HCDR2 comprising the amino acid sequence of positions 50-66 of SEQ ID NO: 138, and an HCDR3 comprising the amino acid sequence of positions 99-108 of SEQ ID NO: 138, and a VL comprising an LCDR1 comprising the amino acid sequence of residues 24-38 of SEQ ID NO: 170, an LCDR2 comprising the amino acid sequence of residues 54-60 of SEQ ID NO: 170, and an LCDR3 comprising the amino acid sequence of residues 93-101 of SEQ ID NO: 170;- a VH comprising an HCDR1 comprising the amino acid sequence of positions 26-35 of SEQ ID NO: 140, an HCDR2 comprising the amino acid sequence of positions 50-66 of SEQ ID NO: 140, and an HCDR3 comprising the amino acid sequence of positions 99-108 of SEQ ID NO: 140, and a VL comprising an LCDR1 comprising the amino acid sequence of residues 24-38 of SEQ ID NO: 170, an LCDR2 comprising the amino acid sequence of residues 54-60 of SEQ ID NO: 170, and an LCDR3 comprising the amino acid sequence of residues 93-101 of SEQ ID NO: 170;- a VH comprising an HCDR1 comprising the amino acid sequence of positions 26-35 of SEQ ID NO: 142, an HCDR2 comprising the amino acid sequence of positions 50-66 of SEQ ID NO: 142, and an HCDR3 comprising the amino acid sequence of positions 99-108 of SEQ ID NO: 142, and a VL comprising an LCDR1 comprising the amino acid sequence of residues 24-38 of SEQ ID NO: 170, an LCDR2 comprising the amino acid sequence of residues 54-60 of SEQ ID NO: 170, and an LCDR3 comprising the amino acid sequence of residues 93-101 of SEQ ID NO: 170;- a VH comprising an HCDR1 comprising the amino acid sequence of positions 26-35 of SEQ ID NO: 144, an HCDR2 comprising the amino acid sequence of positions 50-66 of SEQ ID NO: 144, and an HCDR3 comprising the amino acid sequence of positions 99-108 of SEQ ID NO: 144, and a VL comprising an LCDR1 comprising the amino acid sequence of residues 24-38 of SEQ ID NO: 170, an LCDR2 comprising the amino acid sequence ofresidues 54-60 of SEQ ID NO: 170, and an LCDR3 comprising the amino acid sequence of residues 93-101 of SEQ ID NO: 170;- a VH comprising an HCDR1 comprising the amino acid sequence of positions 26-35 of SEQ ID NO: 146, an HCDR2 comprising the amino acid sequence of positions 50-66 of SEQ ID NO: 146, and an HCDR3 comprising the amino acid sequence of positions 99-108 of SEQ ID NO: 146, and a VL comprising an LCDR1 comprising the amino acid sequence of residues 24-38 of SEQ ID NO: 170, an LCDR2 comprising the amino acid sequence of residues 54-60 of SEQ ID NO: 170, and an LCDR3 comprising the amino acid sequence of residues 93-101 of SEQ ID NO: 170;- a VH comprising an HCDR1 comprising the amino acid sequence of positions 26-35 of SEQ ID NO: 148, an HCDR2 comprising the amino acid sequence of positions 50-66 of SEQ ID NO: 148, and an HCDR3 comprising the amino acid sequence of positions 99-108 of SEQ ID NO: 148, and a VL comprising an LCDR1 comprising the amino acid sequence of residues 24-38 of SEQ ID NO: 170, an LCDR2 comprising the amino acid sequence of residues 54-60 of SEQ ID NO: 170, and an LCDR3 comprising the amino acid sequence of residues 93-101 of SEQ ID NO: 170;- a VH comprising an HCDR1 comprising the amino acid sequence of positions 26-35 of SEQ ID NO: 150, an HCDR2 comprising the amino acid sequence of positions 50-66 of SEQ ID NO: 150, and an HCDR3 comprising the amino acid sequence of positions 99-108 of SEQ ID NO: 150, and a VL comprising an LCDR1 comprising the amino acid sequence of residues 24-38 of SEQ ID NO: 170, an LCDR2 comprising the amino acid sequence of residues 54-60 of SEQ ID NO: 170, and an LCDR3 comprising the amino acid sequence of residues 93-101 of SEQ ID NO: 170;- a VH comprising an HCDR1 comprising the amino acid sequence of positions 26-35 of SEQ ID NO: 152, an HCDR2 comprising the amino acid sequence of positions 50-66 of SEQ ID NO: 152, and an HCDR3 comprising the amino acid sequence of positions 99-108 of SEQ ID NO: 152, and a VL comprising an LCDR1 comprising the amino acid sequence of residues 24-38 of SEQ ID NO: 170, an LCDR2 comprising the amino acid sequence of residues 54-60 of SEQ ID NO: 170, and an LCDR3 comprising the amino acid sequence of residues 93-101 of SEQ ID NO: 170;- a VH comprising an HCDR1 comprising the amino acid sequence of positions 26-35 of SEQ ID NO: 154, an HCDR2 comprising the amino acid sequence of positions 50-66 of SEQ ID NO: 154, and an HCDR3 comprising the amino acid sequence of positions 99-108 ofSEQ ID NO: 154, and a VL comprising an LCDR1 comprising the amino acid sequence of residues 24-38 of SEQ ID NO: 170, an LCDR2 comprising the amino acid sequence of residues 54-60 of SEQ ID NO: 170, and an LCDR3 comprising the amino acid sequence of residues 93-101 of SEQ ID NO: 170;- a VH comprising an HCDR1 comprising the amino acid sequence of positions 26-35 of SEQ ID NO: 156, an HCDR2 comprising the amino acid sequence of positions 50-66 of SEQ ID NO: 156, and an HCDR3 comprising the amino acid sequence of positions 99-108 of SEQ ID NO: 156, and a VL comprising an LCDR1 comprising the amino acid sequence of residues 24-38 of SEQ ID NO: 170, an LCDR2 comprising the amino acid sequence of residues 54-60 of SEQ ID NO: 170, and an LCDR3 comprising the amino acid sequence of residues 93-101 of SEQ ID NO: 170;- a VH comprising an HCDR1 comprising the amino acid sequence of positions 26-35 of SEQ ID NO: 158, an HCDR2 comprising the amino acid sequence of positions 50-66 of SEQ ID NO: 158, and an HCDR3 comprising the amino acid sequence of positions 99-108 of SEQ ID NO: 158, and a VL comprising an LCDR1 comprising the amino acid sequence of residues 24-38 of SEQ ID NO: 170, an LCDR2 comprising the amino acid sequence of residues 54-60 of SEQ ID NO: 170, and an LCDR3 comprising the amino acid sequence of residues 93-101 of SEQ ID NO: 170;- a VH comprising an HCDR1 comprising the amino acid sequence of positions 26-35 of SEQ ID NO: 160, an HCDR2 comprising the amino acid sequence of positions 50-66 of SEQ ID NO: 160, and an HCDR3 comprising the amino acid sequence of positions 99-108 of SEQ ID NO: 160, and a VL comprising an LCDR1 comprising the amino acid sequence of residues 24-38 of SEQ ID NO: 170, an LCDR2 comprising the amino acid sequence of residues 54-60 of SEQ ID NO: 170, and an LCDR3 comprising the amino acid sequence of residues 93-101 of SEQ ID NO: 170;- a VH comprising an HCDR1 comprising the amino acid sequence of positions 26-35 of SEQ ID NO: 162, an HCDR2 comprising the amino acid sequence of positions 50-66 of SEQ ID NO: 162, and an HCDR3 comprising the amino acid sequence of positions 99-108 of SEQ ID NO: 162, and a VL comprising an LCDR1 comprising the amino acid sequence of residues 24-38 of SEQ ID NO: 170, an LCDR2 comprising the amino acid sequence of residues 54-60 of SEQ ID NO: 170, and an LCDR3 comprising the amino acid sequence of residues 93-101 of SEQ ID NO: 170;- a VH comprising an HCDR1 comprising the amino acid sequence of positions 26-35 of SEQ ID NO: 164, an HCDR2 comprising the amino acid sequence of positions 50-66 of SEQ ID NO: 164, and an HCDR3 comprising the amino acid sequence of positions 99-108 of SEQ ID NO: 164, and a VL comprising an LCDR1 comprising the amino acid sequence of residues 24-38 of SEQ ID NO: 170, an LCDR2 comprising the amino acid sequence of residues 54-60 of SEQ ID NO: 170, and an LCDR3 comprising the amino acid sequence of residues 93-101 of SEQ ID NO: 170;- a VH comprising an HCDR1 comprising the amino acid sequence of positions 26-35 of SEQ ID NO: 166, an HCDR2 comprising the amino acid sequence of positions 50-66 of SEQ ID NO: 166, and an HCDR3 comprising the amino acid sequence of positions 99-108 of SEQ ID NO: 166, and a VL comprising an LCDR1 comprising the amino acid sequence of residues 24-38 of SEQ ID NO: 170, an LCDR2 comprising the amino acid sequence of residues 54-60 of SEQ ID NO: 170, and an LCDR3 comprising the amino acid sequence of residues 93-101 of SEQ ID NO: 170; or- a VH comprising an HCDR1 comprising the amino acid sequence of positions 26-35 of SEQ ID NO: 168, an HCDR2 comprising the amino acid sequence of positions 50-66 of SEQ ID NO: 168, and an HCDR3 comprising the amino acid sequence of positions 99-108 of SEQ ID NO: 168, and a VL comprising an LCDR1 comprising the amino acid sequence of residues 24-38 of SEQ ID NO: 170, an LCDR2 comprising the amino acid sequence of residues 54-60 of SEQ ID NO: 170, and an LCDR3 comprising the amino acid sequence of residues 93-101 of SEQ ID NO: 170.In some embodiments, the antibody comprises:- a VH comprising an HCDR1 comprising the amino acid sequence of positions 26-35 of SEQ ID NO: 138, an HCDR2 comprising the amino acid sequence of positions 50-66 of SEQ ID NO: 138, and an HCDR3 comprising the amino acid sequence of positions 99-108 of SEQ ID NO: 138, and a VL comprising an LCDR1 comprising the amino acid sequence of residues 24-38 of SEQ ID NO: 172, an LCDR2 comprising the amino acid sequence of residues 54-60 of SEQ ID NO: 172, and an LCDR3 comprising the amino acid sequence of residues 93-101 of SEQ ID NO: 172;- a VH comprising an HCDR1 comprising the amino acid sequence of positions 26-35 of SEQ ID NO: 140, an HCDR2 comprising the amino acid sequence of positions 50-66 of SEQ ID NO: 140, and an HCDR3 comprising the amino acid sequence of positions 99-108 of SEQ ID NO: 140, and a VL comprising an LCDR1 comprising the amino acid sequence ofresidues 24-38 of SEQ ID NO: 172, an LCDR2 comprising the amino acid sequence of residues 54-60 of SEQ ID NO: 172, and an LCDR3 comprising the amino acid sequence of residues 93-101 of SEQ ID NO: 172;- a VH comprising an HCDR1 comprising the amino acid sequence of positions 26-35 of SEQ ID NO: 142, an HCDR2 comprising the amino acid sequence of positions 50-66 of SEQ ID NO: 142, and an HCDR3 comprising the amino acid sequence of positions 99-108 of SEQ ID NO: 142, and a VL comprising an LCDR1 comprising the amino acid sequence of residues 24-38 of SEQ ID NO: 172, an LCDR2 comprising the amino acid sequence of residues 54-60 of SEQ ID NO: 172, and an LCDR3 comprising the amino acid sequence of residues 93-101 of SEQ ID NO: 172;- a VH comprising an HCDR1 comprising the amino acid sequence of positions 26-35 of SEQ ID NO: 144, an HCDR2 comprising the amino acid sequence of positions 50-66 of SEQ ID NO: 144, and an HCDR3 comprising the amino acid sequence of positions 99-108 of SEQ ID NO: 144, and a VL comprising an LCDR1 comprising the amino acid sequence of residues 24-38 of SEQ ID NO: 172, an LCDR2 comprising the amino acid sequence of residues 54-60 of SEQ ID NO: 172, and an LCDR3 comprising the amino acid sequence of residues 93-101 of SEQ ID NO: 172;- a VH comprising an HCDR1 comprising the amino acid sequence of positions 26-35 of SEQ ID NO: 146, an HCDR2 comprising the amino acid sequence of positions 50-66 of SEQ ID NO: 146, and an HCDR3 comprising the amino acid sequence of positions 99-108 of SEQ ID NO: 146, and a VL comprising an LCDR1 comprising the amino acid sequence of residues 24-38 of SEQ ID NO: 172, an LCDR2 comprising the amino acid sequence of residues 54-60 of SEQ ID NO: 172, and an LCDR3 comprising the amino acid sequence of residues 93-101 of SEQ ID NO: 172;- a VH comprising an HCDR1 comprising the amino acid sequence of positions 26-35 of SEQ ID NO: 148, an HCDR2 comprising the amino acid sequence of positions 50-66 of SEQ ID NO: 148, and an HCDR3 comprising the amino acid sequence of positions 99-108 of SEQ ID NO: 148, and a VL comprising an LCDR1 comprising the amino acid sequence of residues 24-38 of SEQ ID NO: 172, an LCDR2 comprising the amino acid sequence of residues 54-60 of SEQ ID NO: 172, and an LCDR3 comprising the amino acid sequence of residues 93-101 of SEQ ID NO: 172;- a VH comprising an HCDR1 comprising the amino acid sequence of positions 26-35 of SEQ ID NO: 150, an HCDR2 comprising the amino acid sequence of positions 50-66 ofSEQ ID NO: 150, and an HCDR3 comprising the amino acid sequence of positions 99-108 of SEQ ID NO: 150, and a VL comprising an LCDR1 comprising the amino acid sequence of residues 24-38 of SEQ ID NO: 172, an LCDR2 comprising the amino acid sequence of residues 54-60 of SEQ ID NO: 172, and an LCDR3 comprising the amino acid sequence of residues 93-101 of SEQ ID NO: 172;- a VH comprising an HCDR1 comprising the amino acid sequence of positions 26-35 of SEQ ID NO: 152, an HCDR2 comprising the amino acid sequence of positions 50-66 of SEQ ID NO: 152, and an HCDR3 comprising the amino acid sequence of positions 99-108 of SEQ ID NO: 152, and a VL comprising an LCDR1 comprising the amino acid sequence of residues 24-38 of SEQ ID NO: 172, an LCDR2 comprising the amino acid sequence of residues 54-60 of SEQ ID NO: 172, and an LCDR3 comprising the amino acid sequence of residues 93-101 of SEQ ID NO: 172;- a VH comprising an HCDR1 comprising the amino acid sequence of positions 26-35 of SEQ ID NO: 154, an HCDR2 comprising the amino acid sequence of positions 50-66 of SEQ ID NO: 154, and an HCDR3 comprising the amino acid sequence of positions 99-108 of SEQ ID NO: 154, and a VL comprising an LCDR1 comprising the amino acid sequence of residues 24-38 of SEQ ID NO: 172, an LCDR2 comprising the amino acid sequence of residues 54-60 of SEQ ID NO: 172, and an LCDR3 comprising the amino acid sequence of residues 93-101 of SEQ ID NO: 172;- a VH comprising an HCDR1 comprising the amino acid sequence of positions 26-35 of SEQ ID NO: 156, an HCDR2 comprising the amino acid sequence of positions 50-66 of SEQ ID NO: 156, and an HCDR3 comprising the amino acid sequence of positions 99-108 of SEQ ID NO: 156, and a VL comprising an LCDR1 comprising the amino acid sequence of residues 24-38 of SEQ ID NO: 172, an LCDR2 comprising the amino acid sequence of residues 54-60 of SEQ ID NO: 172, and an LCDR3 comprising the amino acid sequence of residues 93-101 of SEQ ID NO: 172;- a VH comprising an HCDR1 comprising the amino acid sequence of positions 26-35 of SEQ ID NO: 158, an HCDR2 comprising the amino acid sequence of positions 50-66 of SEQ ID NO: 158, and an HCDR3 comprising the amino acid sequence of positions 99-108 of SEQ ID NO: 158, and a VL comprising an LCDR1 comprising the amino acid sequence of residues 24-38 of SEQ ID NO: 172, an LCDR2 comprising the amino acid sequence of residues 54-60 of SEQ ID NO: 172, and an LCDR3 comprising the amino acid sequence of residues 93-101 of SEQ ID NO: 172;- a VH comprising an HCDR1 comprising the amino acid sequence of positions 26-35 of SEQ ID NO: 160, an HCDR2 comprising the amino acid sequence of positions 50-66 of SEQ ID NO: 160, and an HCDR3 comprising the amino acid sequence of positions 99-108 of SEQ ID NO: 160, and a VL comprising an LCDR1 comprising the amino acid sequence of residues 24-38 of SEQ ID NO: 172, an LCDR2 comprising the amino acid sequence of residues 54-60 of SEQ ID NO: 172, and an LCDR3 comprising the amino acid sequence of residues 93-101 of SEQ ID NO: 172;- a VH comprising an HCDR1 comprising the amino acid sequence of positions 26-35 of SEQ ID NO: 162, an HCDR2 comprising the amino acid sequence of positions 50-66 of SEQ ID NO: 162, and an HCDR3 comprising the amino acid sequence of positions 99-108 of SEQ ID NO: 162, and a VL comprising an LCDR1 comprising the amino acid sequence of residues 24-38 of SEQ ID NO: 172, an LCDR2 comprising the amino acid sequence of residues 54-60 of SEQ ID NO: 172, and an LCDR3 comprising the amino acid sequence of residues 93-101 of SEQ ID NO: 172;- a VH comprising an HCDR1 comprising the amino acid sequence of positions 26-35 of SEQ ID NO: 164, an HCDR2 comprising the amino acid sequence of positions 50-66 of SEQ ID NO: 164, and an HCDR3 comprising the amino acid sequence of positions 99-108 of SEQ ID NO: 164, and a VL comprising an LCDR1 comprising the amino acid sequence of residues 24-38 of SEQ ID NO: 172, an LCDR2 comprising the amino acid sequence of residues 54-60 of SEQ ID NO: 172, and an LCDR3 comprising the amino acid sequence of residues 93-101 of SEQ ID NO: 172;- a VH comprising an HCDR1 comprising the amino acid sequence of positions 26-35 of SEQ ID NO: 166, an HCDR2 comprising the amino acid sequence of positions 50-66 of SEQ ID NO: 166, and an HCDR3 comprising the amino acid sequence of positions 99-108 of SEQ ID NO: 166, and a VL comprising an LCDR1 comprising the amino acid sequence of residues 24-38 of SEQ ID NO: 172, an LCDR2 comprising the amino acid sequence of residues 54-60 of SEQ ID NO: 172, and an LCDR3 comprising the amino acid sequence of residues 93-101 of SEQ ID NO: 172; or- a VH comprising an HCDR1 comprising the amino acid sequence of positions 26-35 of SEQ ID NO: 168, an HCDR2 comprising the amino acid sequence of positions 50-66 of SEQ ID NO: 168, and an HCDR3 comprising the amino acid sequence of positions 99-108 of SEQ ID NO: 168, and a VL comprising an LCDR1 comprising the amino acid sequence of residues 24-38 of SEQ ID NO: 172, an LCDR2 comprising the amino acid sequence ofresidues 54-60 of SEQ ID NO: 172, and an LCDR3 comprising the amino acid sequence of residues 93-101 of SEQ ID NO: 172.In some embodiments above, the antibody comprises a VH comprising an amino acid sequence that is at least 90% identical to, at least 95% identical to, or at least 97% identical to the amino acid sequence of SEQ ID NO: 138, SEQ ID NO: 140, SEQ ID NO: 142, SEQ ID NO: 144, SEQ ID NO: 146, SEQ ID NO: 148, SEQ ID NO: 150, SEQ ID NO: 152, SEQ ID NO: 154, SEQ ID NO: 156, SEQ ID NO: 158, SEQ ID NO: 160, SEQ ID NO: 162, SEQ ID NO: 164, SEQ ID NO: 166, or SEQ ID NO: 168. In some embodiments above, the antibody comprises a VL comprising an amino acid sequence that is at least 90% identical to, at least 95% identical to, or at least 97% identical to the amino acid sequence of SEQ ID NO: 170. In other embodiments, the antibody comprises a VL comprising an amino acid sequence that is at least 90% identical to, at least 95% identical to, or at least 97% identical to the amino acid sequence of SEQ ID NO: 172. In some embodiments, the antibody further comprises the corresponding HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 as provided above.In some embodiments above, the antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 138, SEQ ID NO: 140, SEQ ID NO: 142, SEQ ID NO: 144, SEQ ID NO: 146, SEQ ID NO: 148, SEQ ID NO: 150, SEQ ID NO: 152, SEQ ID NO: 154, SEQ ID NO: 156, SEQ ID NO: 158, SEQ ID NO: 160, SEQ ID NO: 162, SEQ ID NO: 164, SEQ ID NO: 166, or SEQ ID NO: 168. In some embodiments above, the antibody comprises a VL comprising the amino acid sequence of SEQ ID NO: 170. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID NO: 172. In some embodiments above, the antibody comprises a VH comprising the amino acid sequence ofSEQ ID NO: 138, SEQ ID NO: 140, SEQ ID NO: 142, SEQ ID NO: 144, SEQ ID NO: 146,SEQ ID NO: 148, SEQ ID NO: 150, SEQ ID NO: 152, SEQ ID NO: 154, SEQ ID NO: 156,SEQ ID NO: 158, SEQ ID NO: 160, SEQ ID NO: 162, SEQ ID NO: 164, SEQ ID NO: 166, or SEQ ID NO: 168, and also a VL comprising the amino acid sequence of SEQ ID NO: 170. In some embodiments above, the antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 138, SEQ ID NO: 140, SEQ ID NO: 142, SEQ ID NO: 144, SEQ ID NO: 146, SEQ ID NO: 148, SEQ ID NO: 150, SEQ ID NO: 152, SEQ ID NO: 154, SEQ ID NO: 156, SEQ ID NO: 158, SEQ ID NO: 160, SEQ ID NO: 162, SEQ ID NO: 164, SEQ ID NO: 166, or SEQ ID NO: 168, and also a VL comprising the amino acid sequence of SEQ ID NO: 172.In some embodiments, the disclosure relates to an isolated antibody that specifically binds to protein arginine deiminase 4 (PAD4), wherein the antibody comprises a heavy chain variable region (VH) comprising a heavy chain complementarity determining region 1 (HCDR1) comprising the amino acid sequence of positions 26-35 of SEQ ID NO: 138, an HCDR2 comprising the amino acid sequence of positions 50-66 of SEQ ID NO: 138, and an HCDR3 comprising the amino acid sequence of positions 99-108 of SEQ ID NO: 138; and a light chain variable region (VL) comprising a light chain complementarity determining region 1 (LCDR1) comprising the amino acid sequence residues 24-38 of SEQ ID NO: 170, an LCDR2 comprising the amino acid sequence of residues 54-60 of SEQ ID NO: 170, and an LCDR3 comprising the amino acid sequence of residues 93-101 of SEQ ID NO: 170. In some embodiments, the antibody comprises a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 138. In some embodiments, the antibody comprises a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 170. In some embodiments, the antibody comprises both a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 138; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 170. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 138 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 170 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises both a VH comprising the amino acid sequence of SEQ ID No: 138 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID No: 170 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 172. In some embodiments, the antibody comprises both a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 138; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 172. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 138 modified by 1-10 amino acidsubstitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 172 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises both a VH comprising the amino acid sequence of SEQ ID No: 138 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID No: 172 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions.In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 138. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 138; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 170. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 170. In some embodiments, the antibody comprises a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 138; and a VL comprising the amino acid sequence of SEQ ID No: 170. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 138 and a VL comprising the amino acid sequence of SEQ ID No: 170.In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 138. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 138; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 172. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 172. In some embodiments, the antibody comprises a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 138; and a VL comprising the amino acid sequence of SEQ ID No: 172. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 138 and a VL comprising the amino acid sequence of SEQ ID No: 172.In some embodiments, the disclosure relates to an isolated antibody that specifically binds to protein arginine deiminase 4 (PAD4), wherein the antibody comprises a heavy chain variable region (VH) comprising a heavy chain complementarity determining region 1 (HCDR1) comprising the amino acid sequence of positions 26-35 of SEQ ID NO: 140, an HCDR2 comprising the amino acid sequence of positions 50-66 of SEQ ID NO: 140, and anHCDR3 comprising the amino acid sequence of positions 99-108 of SEQ ID NO: 140; and a light chain variable region (VL) comprising a light chain complementarity determining region 1 (LCDR1) comprising the amino acid sequence residues 24-38 of SEQ ID NO: 170, an LCDR2 comprising the amino acid sequence of residues 54-60 of SEQ ID NO: 170, and an LCDR3 comprising the amino acid sequence of residues 93-101 of SEQ ID NO: 170. In some embodiments, the antibody comprises a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 140. In some embodiments, the antibody comprises a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 170. In some embodiments, the antibody comprises both a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 140; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 170. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 140 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 170 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises both a VH comprising the amino acid sequence of SEQ ID No: 140 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID No: 170 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 172. In some embodiments, the antibody comprises both a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 140; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 172. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 140 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 172 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises both a VH comprising the amino acid sequence of SEQ ID No: 140 modified by 1-10 amino acidsubstitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID No: 172 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions.In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 140. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 140; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 170. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 170. In some embodiments, the antibody comprises a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 140; and a VL comprising the amino acid sequence of SEQ ID No: 170. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 140 and a VL comprising the amino acid sequence of SEQ ID No: 170.In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 140. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 140; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 172. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 172. In some embodiments, the antibody comprises a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 140; and a VL comprising the amino acid sequence of SEQ ID No: 172. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 140 and a VL comprising the amino acid sequence of SEQ ID No: 172.In some embodiments, the disclosure relates to an isolated antibody that specifically binds to protein arginine deiminase 4 (PAD4), wherein the antibody comprises a heavy chain variable region (VH) comprising a heavy chain complementarity determining region 1 (HCDR1) comprising the amino acid sequence of positions 26-35 of SEQ ID NO: 142, an HCDR2 comprising the amino acid sequence of positions 50-66 of SEQ ID NO: 142, and an HCDR3 comprising the amino acid sequence of positions 99-108 of SEQ ID NO: 142; and a light chain variable region (VL) comprising a light chain complementarity determining region 1 (LCDR1) comprising the amino acid sequence residues 24-38 of SEQ ID NO: 170, an LCDR2 comprising the amino acid sequence of residues 54-60 of SEQ ID NO: 170, and an LCDR3 comprising the amino acid sequence of residues 93-101 of SEQ ID NO: 170. Insome embodiments, the antibody comprises a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 142. In some embodiments, the antibody comprises a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 170. In some embodiments, the antibody comprises both a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 142; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 170. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 142 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 170 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises both a VH comprising the amino acid sequence of SEQ ID No: 142 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID No: 170 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 172. In some embodiments, the antibody comprises both a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 142; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 172. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 142 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 172 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises both a VH comprising the amino acid sequence of SEQ ID No: 142 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID No: 172 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions.In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 142. In some embodiments, the antibody comprises a VHcomprising the amino acid sequence of SEQ ID No: 142; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 170. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 170. In some embodiments, the antibody comprises a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 142; and a VL comprising the amino acid sequence of SEQ ID No: 170. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 142 and a VL comprising the amino acid sequence of SEQ ID No: 170.In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 142. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 142; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 172. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 172. In some embodiments, the antibody comprises a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 142; and a VL comprising the amino acid sequence of SEQ ID No: 172. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 142 and a VL comprising the amino acid sequence of SEQ ID No: 172.In some embodiments, the disclosure relates to an isolated antibody that specifically binds to protein arginine deiminase 4 (PAD4), wherein the antibody comprises a heavy chain variable region (VH) comprising a heavy chain complementarity determining region 1 (HCDR1) comprising the amino acid sequence of positions 26-35 of SEQ ID NO: 144, an HCDR2 comprising the amino acid sequence of positions 50-66 of SEQ ID NO: 144, and an HCDR3 comprising the amino acid sequence of positions 99-108 of SEQ ID NO: 144; and a light chain variable region (VL) comprising a light chain complementarity determining region 1 (LCDR1) comprising the amino acid sequence residues 24-38 of SEQ ID NO: 170, an LCDR2 comprising the amino acid sequence of residues 54-60 of SEQ ID NO: 170, and an LCDR3 comprising the amino acid sequence of residues 93-101 of SEQ ID NO: 170. In some embodiments, the antibody comprises a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 144. In some embodiments, the antibody comprises a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 170. In some embodiments, the antibody comprises both a VH that is at least 90%, at least 95%, at least 97%, or at least99% identical to the amino acid sequence of SEQ ID NO: 144; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 170. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 144 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 170 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises both a VH comprising the amino acid sequence of SEQ ID No: 144 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID No: 170 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 172. In some embodiments, the antibody comprises both a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 144; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% Identical to the amino acid sequence of SEQ ID NO: 172. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 144 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 172 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises both a VH comprising the amino acid sequence of SEQ ID No: 144 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID No: 172 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions.In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 144. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 144; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 170. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 170. In some embodiments, the antibody comprises a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence ofSEQ ID NO: 144; and a VL comprising the amino acid sequence of SEQ ID No: 170. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 144 and a VL comprising the amino acid sequence of SEQ ID No: 170.In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 144. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 144; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 172. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 172. In some embodiments, the antibody comprises a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 144; and a VL comprising the amino acid sequence of SEQ ID No: 172. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 144 and a VL comprising the amino acid sequence of SEQ ID No: 172.In some embodiments, the disclosure relates to an isolated antibody that specifically binds to protein arginine deiminase 4 (PAD4), wherein the antibody comprises a heavy chain variable region (VH) comprising a heavy chain complementarity determining region 1 (HCDR1) comprising the amino acid sequence of positions 26-35 of SEQ ID NO: 146, an HCDR2 comprising the amino acid sequence of positions 50-66 of SEQ ID NO: 146, and an HCDR3 comprising the amino acid sequence of positions 99-108 of SEQ ID NO: 146; and a light chain variable region (VL) comprising a light chain complementarity determining region 1 (LCDR1) comprising the amino acid sequence residues 24-38 of SEQ ID NO: 170, an LCDR2 comprising the amino acid sequence of residues 54-60 of SEQ ID NO: 170, and an LCDR3 comprising the amino acid sequence of residues 93-101 of SEQ ID NO: 170. In some embodiments, the antibody comprises a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 146. In some embodiments, the antibody comprises a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 170. In some embodiments, the antibody comprises both a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 146; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 170. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 146 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprisesa VL comprising the amino acid sequence of SEQ ID No: 170 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises both a VH comprising the amino acid sequence of SEQ ID No: 146 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID No: 170 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 172. In some embodiments, the antibody comprises both a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 146; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 172. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 146 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 172 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises both a VH comprising the amino acid sequence of SEQ ID No: 146 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID No: 172 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions.In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 146. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 146; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 170. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 170. In some embodiments, the antibody comprises a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 146; and a VL comprising the amino acid sequence of SEQ ID No: 170. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 146 and a VL comprising the amino acid sequence of SEQ ID No: 170.In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 146. In some embodiments, the antibody comprises a VHcomprising the amino acid sequence of SEQ ID No: 146; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 172. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 172. In some embodiments, the antibody comprises a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 146; and a VL comprising the amino acid sequence of SEQ ID No: 172. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 146 and a VL comprising the amino acid sequence of SEQ ID No: 172.In some embodiments, the disclosure relates to an isolated antibody that specifically binds to protein arginine deiminase 4 (PAD4), wherein the antibody comprises a heavy chain variable region (VH) comprising a heavy chain complementarity determining region 1 (HCDR1) comprising the amino acid sequence of positions 26-35 of SEQ ID NO: 148, an HCDR2 comprising the amino acid sequence of positions 50-66 of SEQ ID NO: 148, and an HCDR3 comprising the amino acid sequence of positions 99-108 of SEQ ID NO: 148; and a light chain variable region (VL) comprising a light chain complementarity determining region 1 (LCDR1) comprising the amino acid sequence residues 24-38 of SEQ ID NO: 170, an LCDR2 comprising the amino acid sequence of residues 54-60 of SEQ ID NO: 170, and an LCDR3 comprising the amino acid sequence of residues 93-101 of SEQ ID NO: 170. In some embodiments, the antibody comprises a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 148. In some embodiments, the antibody comprises a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 170. In some embodiments, the antibody comprises both a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 148; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 170. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 148 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 170 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises both a VH comprising the amino acid sequence of SEQ ID No: 148 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID No: 170modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 172. In some embodiments, the antibody comprises both a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 148; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 172. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 148 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 172 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises both a VH comprising the amino acid sequence of SEQ ID No: 148 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID No: 172 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions.In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 148. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 148; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 170. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 170. In some embodiments, the antibody comprises a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 148; and a VL comprising the amino acid sequence of SEQ ID No: 170. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 148 and a VL comprising the amino acid sequence of SEQ ID No: 170.In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 148. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 148; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 172. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 172. In some embodiments, the antibody comprises a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence ofSEQ ID NO: 148; and a VL comprising the amino acid sequence of SEQ ID No: 172. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 148 and a VL comprising the amino acid sequence of SEQ ID No: 172.In some embodiments, the disclosure relates to an isolated antibody that specifically binds to protein arginine deiminase 4 (PAD4), wherein the antibody comprises a heavy chain variable region (VH) comprising a heavy chain complementarity determining region 1 (HCDR1) comprising the amino acid sequence of positions 26-35 of SEQ ID NO: 150, an HCDR2 comprising the amino acid sequence of positions 50-66 of SEQ ID NO: 150, and an HCDR3 comprising the amino acid sequence of positions 99-108 of SEQ ID NO: 150; and a light chain variable region (VL) comprising a light chain complementarity determining region 1 (LCDR1) comprising the amino acid sequence residues 24-38 of SEQ ID NO: 170, an LCDR2 comprising the amino acid sequence of residues 54-60 of SEQ ID NO: 170, and an LCDR3 comprising the amino acid sequence of residues 93-101 of SEQ ID NO: 170. In some embodiments, the antibody comprises a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 150. In some embodiments, the antibody comprises a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 170. In some embodiments, the antibody comprises both a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 150; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 170. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 150 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 170 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises both a VH comprising the amino acid sequence of SEQ ID No: 150 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID No: 170 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 172. In some embodiments, the antibody comprises both a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 150; and aVL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 172. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 150 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 172 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises both a VH comprising the amino acid sequence of SEQ ID No: 150 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID No: 172 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions.In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 150. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 150; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 170. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 170. In some embodiments, the antibody comprises a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 150; and a VL comprising the amino acid sequence of SEQ ID No: 170. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 150 and a VL comprising the amino acid sequence of SEQ ID No: 170.In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 150. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 150; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 172. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 172. In some embodiments, the antibody comprises a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 150; and a VL comprising the amino acid sequence of SEQ ID No: 172. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 150 and a VL comprising the amino acid sequence of SEQ ID No: 172.In some embodiments, the methods can be used to assess an antibody that specifically binds to protein arginine deiminase 4 (PAD4), and comprises a heavy chain variable region(VH) comprising a heavy chain complementarity determining region 1 (HCDR1) comprising the amino acid sequence of positions 26-35 of SEQ ID NO: 152, an HCDR2 comprising the amino acid sequence of positions 50-66 of SEQ ID NO: 152, and an HCDR3 comprising the amino acid sequence of positions 99-108 of SEQ ID NO: 152; and a light chain variable region (VL) comprising a light chain complementarity determining region 1 (LCDR1) comprising the amino acid sequence residues 24-38 of SEQ ID NO: 170, an LCDR2 comprising the amino acid sequence of residues 54-60 of SEQ ID NO: 170, and an LCDR3 comprising the amino acid sequence of residues 93-101 of SEQ ID NO: 170. In some embodiments, the antibody comprises a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 152. In some embodiments, the antibody comprises a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 170. In some embodiments, the antibody comprises both a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 152; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 170. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 152 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 170 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises both a VH comprising the amino acid sequence of SEQ ID No: 152 modified by 1- 10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID No: 170 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 172. In some embodiments, the antibody comprises both a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 152; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 172. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 152 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 172 modified by 1-10 amino acidsubstitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises both a VH comprising the amino acid sequence of SEQ ID No: 152 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID No: 172 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions.In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 152. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 152; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 170. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 170. In some embodiments, the antibody comprises a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 152; and a VL comprising the amino acid sequence of SEQ ID No: 170. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 152 and a VL comprising the amino acid sequence of SEQ ID No: 170.In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 152. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 152; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 172. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 172. In some embodiments, the antibody comprises a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 152; and a VL comprising the amino acid sequence of SEQ ID No: 172. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 152 and a VL comprising the amino acid sequence of SEQ ID No: 172.In some embodiments, the antibody comprises a heavy chain variable region (VH) comprising a heavy chain complementarity determining region 1 (HCDR1) comprising the amino acid sequence of positions 26-35 of SEQ ID NO: 154, an HCDR2 comprising the amino acid sequence of positions 50-66 of SEQ ID NO: 154, and an HCDR3 comprising the amino acid sequence of positions 99-108 of SEQ ID NO: 154; and a light chain variable region (VL) comprising a light chain complementarity determining region 1 (LCDR1) comprising the amino acid sequence residues 24-38 of SEQ ID NO: 170, an LCDR2comprising the amino acid sequence of residues 54-60 of SEQ ID NO: 170, and an LCDR3 comprising the amino acid sequence of residues 93-101 of SEQ ID NO: 170. In some embodiments, the antibody comprises a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 154. In some embodiments, the antibody comprises a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 170. In some embodiments, the antibody comprises both a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 154; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 170. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 154 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 170 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises both a VH comprising the amino acid sequence of SEQ ID No: 154 modified by 1- 10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID No: 170 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 172. In some embodiments, the antibody comprises both a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 154; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 172. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 154 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 172 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises both a VH comprising the amino acid sequence of SEQ ID No: 154 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID No: 172 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions.In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 154. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 154; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 170. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 170. In some embodiments, the antibody comprises a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 154; and a VL comprising the amino acid sequence of SEQ ID No: 170. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 154 and a VL comprising the amino acid sequence of SEQ ID No: 170.In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 154. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 154; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 172. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 172. In some embodiments, the antibody comprises a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 154; and a VL comprising the amino acid sequence of SEQ ID No: 172. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 154 and a VL comprising the amino acid sequence of SEQ ID No: 172.In some embodiments, the methods may be used to assess an antibody that specifically binds to protein arginine deiminase 4 (PAD4), wherein the antibody comprises a heavy chain variable region (VH) comprising a heavy chain complementarity determining region 1 (HCDR1) comprising the amino acid sequence of positions 26-35 of SEQ ID NO: 156, an HCDR2 comprising the amino acid sequence of positions 50-66 of SEQ ID NO: 156, and an HCDR3 comprising the amino acid sequence of positions 99-108 of SEQ ID NO: 156; and a light chain variable region (VL) comprising a light chain complementarity determining region 1 (LCDR1) comprising the amino acid sequence residues 24-38 of SEQ ID NO: 170, an LCDR2 comprising the amino acid sequence of residues 54-60 of SEQ ID NO: 170, and an LCDR3 comprising the amino acid sequence of residues 93-101 of SEQ ID NO: 170. In some embodiments, the antibody comprises a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 156. In some embodiments, the antibody comprises a VL that is at least 90%, at least 95%, at least 97%, orat least 99% identical to the amino acid sequence of SEQ ID NO: 170. In some embodiments, the antibody comprises both a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 156; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 170. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 156 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 170 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises both a VH comprising the amino acid sequence of SEQ ID No: 156 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID No: 170 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 172. In some embodiments, the antibody comprises both a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 156; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 172. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 156 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 172 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises both a VH comprising the amino acid sequence of SEQ ID No: 156 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID No: 172 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions.In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 156. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 156; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 170. In some embodiments, the antibody comprises a VL comprising the amino acidsequence of SEQ ID No: 170. In some embodiments, the antibody comprises a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 156; and a VL comprising the amino acid sequence of SEQ ID No: 170. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 156 and a VL comprising the amino acid sequence of SEQ ID No: 170.In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 156. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 156; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 172. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 172. In some embodiments, the antibody comprises a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 156; and a VL comprising the amino acid sequence of SEQ ID No: 172. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 156 and a VL comprising the amino acid sequence of SEQ ID No: 172.In some embodiments, the antibody specifically binds to protein arginine deiminase 4 (PAD4), wherein the antibody comprises a heavy chain variable region (VH) comprising a heavy chain complementarity determining region 1 (HCDR1) comprising the amino acid sequence of positions 26-35 of SEQ ID NO: 158, an HCDR2 comprising the amino acid sequence of positions 50-66 of SEQ ID NO: 158, and an HCDR3 comprising the amino acid sequence of positions 99-108 of SEQ ID NO: 158; and a light chain variable region (VL) comprising a light chain complementarity determining region 1 (LCDR1) comprising the amino acid sequence residues 24-38 of SEQ ID NO: 170, an LCDR2 comprising the amino acid sequence of residues 54-60 of SEQ ID NO: 170, and an LCDR3 comprising the amino acid sequence of residues 93-101 of SEQ ID NO: 170. In some embodiments, the antibody comprises a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 158. In some embodiments, the antibody comprises a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 170. In some embodiments, the antibody comprises both a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 158; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 170. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 158modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 170 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises both a VH comprising the amino acid sequence of SEQ ID No: 158 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID No: 170 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 172. In some embodiments, the antibody comprises both a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 158; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 172. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 158 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 172 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises both a VH comprising the amino acid sequence of SEQ ID No: 158 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID No: 172 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions.In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 158. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 158; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 170. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 170. In some embodiments, the antibody comprises a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 158; and a VL comprising the amino acid sequence of SEQ ID No: 170. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 158 and a VL comprising the amino acid sequence of SEQ ID No: 170.In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 158. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 158; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 172. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 172. In some embodiments, the antibody comprises a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 158; and a VL comprising the amino acid sequence of SEQ ID No: 172. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 158 and a VL comprising the amino acid sequence of SEQ ID No: 172.In some embodiments, the antibody specifically binds to protein arginine deiminase 4 (PAD4), wherein the antibody comprises a heavy chain variable region (VH) comprising a heavy chain complementarity determining region 1 (HCDR1) comprising the amino acid sequence of positions 26-35 of SEQ ID NO: 160, an HCDR2 comprising the amino acid sequence of positions 50-66 of SEQ ID NO: 160, and an HCDR3 comprising the amino acid sequence of positions 99-108 of SEQ ID NO: 160; and a light chain variable region (VL) comprising a light chain complementarity determining region 1 (LCDR1) comprising the amino acid sequence residues 24-38 of SEQ ID NO: 170, an LCDR2 comprising the amino acid sequence of residues 54-60 of SEQ ID NO: 170, and an LCDR3 comprising the amino acid sequence of residues 93-101 of SEQ ID NO: 170. In some embodiments, the antibody comprises a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 160. In some embodiments, the antibody comprises a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 170. In some embodiments, the antibody comprises both a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 160; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 170. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 160 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 170 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises both a VH comprising the amino acid sequence of SEQ ID No: 160 modified by 1-10 aminoacid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID No: 170 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 172. In some embodiments, the antibody comprises both a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 160; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 172. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 160 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 172 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises both a VH comprising the amino acid sequence of SEQ ID No: 160 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID No: 172 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions.In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 160. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 160; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 170. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 170. In some embodiments, the antibody comprises a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 160; and a VL comprising the amino acid sequence of SEQ ID No: 170. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 160 and a VL comprising the amino acid sequence of SEQ ID No: 170.In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 160. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 160; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 172. In some embodiments, the antibody comprises a VL comprising the amino acidsequence of SEQ ID No: 172. In some embodiments, the antibody comprises a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 160; and a VL comprising the amino acid sequence of SEQ ID No: 172. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 160 and a VL comprising the amino acid sequence of SEQ ID No: 172.In some embodiments, the antibody specifically binds to protein arginine deiminase 4 (PAD4), wherein the antibody comprises a heavy chain variable region (VH) comprising a heavy chain complementarity determining region 1 (HCDR1) comprising the amino acid sequence of positions 26-35 of SEQ ID NO: 162, an HCDR2 comprising the amino acid sequence of positions 50-66 of SEQ ID NO: 162, and an HCDR3 comprising the amino acid sequence of positions 99-108 of SEQ ID NO: 162; and a light chain variable region (VL) comprising a light chain complementarity determining region 1 (LCDR1) comprising the amino acid sequence residues 24-38 of SEQ ID NO: 170, an LCDR2 comprising the amino acid sequence of residues 54-60 of SEQ ID NO: 170, and an LCDR3 comprising the amino acid sequence of residues 93-101 of SEQ ID NO: 170. In some embodiments, the antibody comprises a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 162. In some embodiments, the antibody comprises a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 170. In some embodiments, the antibody comprises both a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 162; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 170. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 162 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 170 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises both a VH comprising the amino acid sequence of SEQ ID No: 162 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID No: 170 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 172. In some embodiments,the antibody comprises both a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 162; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 172. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 162 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 172 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises both a VH comprising the amino acid sequence of SEQ ID No: 162 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID No: 172 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions.In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 162. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 162; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 170. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 170. In some embodiments, the antibody comprises a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 162; and a VL comprising the amino acid sequence of SEQ ID No: 170. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 162 and a VL comprising the amino acid sequence of SEQ ID No: 170.In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 162. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 162; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 172. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 172. In some embodiments, the antibody comprises a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 162; and a VL comprising the amino acid sequence of SEQ ID No: 172. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 162 and a VL comprising the amino acid sequence of SEQ ID No: 172.In some embodiments, the antibody specifically binds to protein arginine deiminase 4 (PAD4), wherein the antibody comprises a heavy chain variable region (VH) comprising a heavy chain complementarity determining region 1 (HCDR1) comprising the amino acid sequence of positions 26-35 of SEQ ID NO: 164, an HCDR2 comprising the amino acid sequence of positions 50-66 of SEQ ID NO: 164, and an HCDR3 comprising the amino acid sequence of positions 99-108 of SEQ ID NO: 164; and a light chain variable region (VL) comprising a light chain complementarity determining region 1 (LCDR1) comprising the amino acid sequence residues 24-38 of SEQ ID NO: 170, an LCDR2 comprising the amino acid sequence of residues 54-60 of SEQ ID NO: 170, and an LCDR3 comprising the amino acid sequence of residues 93-101 of SEQ ID NO: 170. In some embodiments, the antibody comprises a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 164. In some embodiments, the antibody comprises a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 170. In some embodiments, the antibody comprises both a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 164; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 170. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 164 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 170 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises both a VH comprising the amino acid sequence of SEQ ID No: 164 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID No: 170 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 172. In some embodiments, the antibody comprises both a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 164; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 172. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 164 modified by 1-10 amino acid substitutions, 1-5 amino acidsubstitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 172 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises both a VH comprising the amino acid sequence of SEQ ID No: 164 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID No: 172 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions.In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 164. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 164; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 170. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 170. In some embodiments, the antibody comprises a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 164; and a VL comprising the amino acid sequence of SEQ ID No: 170. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 164 and a VL comprising the amino acid sequence of SEQ ID No: 170.In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 164. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 164; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 172. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 172. In some embodiments, the antibody comprises a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 164; and a VL comprising the amino acid sequence of SEQ ID No: 172. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 164 and a VL comprising the amino acid sequence of SEQ ID No: 172.In some embodiments, the antibody specifically binds to protein arginine deiminase 4 (PAD4), wherein the antibody comprises a heavy chain variable region (VH) comprising a heavy chain complementarity determining region 1 (HCDR1) comprising the amino acid sequence of positions 26-35 of SEQ ID NO: 166, an HCDR2 comprising the amino acid sequence of positions 50-66 of SEQ ID NO: 166, and an HCDR3 comprising the amino acidsequence of positions 99-108 of SEQ ID NO: 166; and a light chain variable region (VL) comprising a light chain complementarity determining region 1 (LCDR1) comprising the amino acid sequence residues 24-38 of SEQ ID NO: 170, an LCDR2 comprising the amino acid sequence of residues 54-60 of SEQ ID NO: 170, and an LCDR3 comprising the amino acid sequence of residues 93-101 of SEQ ID NO: 170. In some embodiments, the antibody comprises a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 166. In some embodiments, the antibody comprises a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 170. In some embodiments, the antibody comprises both a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 166; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 170. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 166 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 170 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises both a VH comprising the amino acid sequence of SEQ ID No: 166 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions and a VL comprising the amino acid sequence of SEQ ID No: 170 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 172. In some embodiments, the antibody comprises both a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 166; and a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 172. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID No: 166 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises a VL comprising the amino acid sequence of SEQ ID No: 172 modified by 1-10 amino acid substitutions, 1-5 amino acid substitutions, or 1-3 amino acid substitutions. In some embodiments, the antibody comprises both a VH comprisi...

Claims

What is Claimed is:

1. A method of determining citrullination of a protein or peptide fragment thereof, comprising assessing citrullination of a citrullination site on a protein or a peptide fragment thereof in a biological sample from a subject, wherein the biological sample has been exposed to a PAD4 inhibitor, wherein the citrullination site is selected from one or more of the following:R1391 of proteoglycan 4 (corresponding to R1391 of Q92954),R573 of fibrinogen alpha chain (corresponding to R573 of P02671), R591 of fibrinogen alpha chain (corresponding to R591 of P02671), R573 of complement C3 (corresponding to R573 of PO 1024), R748 of complement C3 (corresponding to R748 of PO 1024),R688 of inter-alpha-trypsin inhibitor heavy chain H4 (corresponding to R688 of QI 4624),R297 of alpha- 1-microglobulin / bikunin precursor (corresponding to R297 of P02760), R715 of alpha-2-macroglobulin (corresponding to R715 of PO 1023), R32 of gel solin (corresponding to R32 of P06396),R59 of haptoglobin (corresponding to R59 of P00738), and R651 of serotransferrin (corresponding to R651 ofP02787).

2. A method of assessing the activity of a PAD4 inhibitor, the method comprising assessing citrullination of a citrullination site on a protein or a peptide fragment thereof that is present in a biological sample from a subject, wherein the biological sample has been exposed to the PAD4 inhibitor, wherein the citrullination site is selected from one or more of the following:R1391 of proteoglycan 4 (corresponding to R1391 of Q92954),R573 of fibrinogen alpha chain (corresponding to R573 of P02671), R591 of fibrinogen alpha chain (corresponding to R591 of P02671), R573 of complement C3 (corresponding to R573 of PO 1024), R748 of complement C3 (corresponding to R748 of PO 1024),R688 of inter-alpha-trypsin inhibitor heavy chain H4 (corresponding to R688 of QI 4624),R297 of alpha- 1-microglobulin / bikunin precursor (corresponding to R297 of P02760), R715 of alpha-2-macroglobulin (corresponding to R715 of P01023), R32 of gel solin (corresponding to R32 of P06396),R59 of haptoglobin (corresponding to R59 of P00738), andR651 of serotransferrin (corresponding to R651 ofP02787).

3. The method of claim 2, wherein the PAD4 inhibitor reduces citrullination at the citrullination site in a dose-dependent manner.

4. The method of claim 1, 2, or 3, wherein the method comprises assessing citrullination of a peptide fragment of the protein, wherein the peptide fragment comprises the citrullination site.

5. The method of any one of claims 1-4, wherein the biological sample has been exposed to a PAD inhibitor in vivo in a subject as a result of the PAD inhibitor being administered to the subject.

6. The method of any one of claims 1-4, wherein the biological sample has been exposed to the PAD inhibitor by contacting the biological sample with the PAD inhibitor ex vivo.

7. The method of any one of claims 1-6, wherein the assessing citrullination of the citrullination site comprises mass spectrometry (MS).

8. The method of any one of claims 1-6, wherein the assessing citrullination of the citrullination site comprises liquid chromatography and mass spectrometry (LC-MS).

9. The method of any one of claims 1-6, wherein the assessing citrullination comprises selective reaction monitoring and chromatographic separation.

10. The method of any one of claims 1-9, wherein assessing citrullination of the citrullination site comprises measuring, in the biological sample, a first concentration of the citrullinated protein or peptide fragment thereof and a second concentration of corresponding total protein.

11. The method of claim 10, wherein assessing citrullination of the citrullination site comprises determining a citrullination ratio, wherein the citrullination ratio is a ratio of the first concentration to the second concentration.

12. The method of claim 11, wherein the method comprises comparing the citrullination ratio to a reference citrullination ratio.

13. The method of claim 12, wherein the reference citrullination ratio is a citrullination ratio determined for a control biological sample.

14. The method of claim 13, wherein the control biological sample is a biological sample that: (a) has not been exposed to a PAD4 modulator or PAD4 inhibitor, (b) is from the same subject, and / or (c) is from the same subject prior to treatment with the PAD4 inhibitor.

15. The method of any one of claims 12-14, wherein the assessing comprises determining a difference between the citrullination ratio for the biological sample and the reference citrullination ratio.

16. The method of any one of claims 1-15, wherein the method comprises contacting the biological sample with exogenous PALM.

17. A method comprising:(i) contacting a biological sample from a subject with exogenous PALM, and(ii) assessing citrullination of a citrullination site on a protein or a peptide fragment thereof that is present in a biological sample; wherein the citrullination site is selected from one or more of the following:R1391 of proteoglycan 4 (corresponding to R1391 of Q92954),R573 of fibrinogen alpha chain (corresponding to R573 of P02671),R591 of fibrinogen alpha chain (corresponding to R591 of P02671),R573 of complement C3 (corresponding to R573 of PO 1024),R748 of complement C3 (corresponding to R748 of PO 1024),R688 of inter-alpha-trypsin inhibitor heavy chain H4 (corresponding to R688 ofQI 4624),R297 of alpha- 1-microglobulin / bikunin precursor (corresponding to R297 of P02760), R715 of alpha-2-macroglobulin (corresponding to R715 of PO 1023), R32 of gel solin (corresponding to R32 of P06396),R59 of haptoglobin (corresponding to R59 of P00738), andR651 of serotransferrin (corresponding to R651 ofP02787).

18. The method of claim 16 or 17, wherein the method comprises incubating the exogenous PALM with the biological sample.

19. The method of claim 18, wherein the method comprises incubating the exogenous PALM with the biological sample at a temperature of 36-38 °C.

20. The method of claim 18 or 19, wherein the incubating is for 1-3 hours.

21. The method of any one of claims 18-20, wherein the method comprises adding EDTA to the biological sample after the incubation with exogenous PAD4.

22. The method of any one of claims 1-21, wherein the method comprises incubating the biological sample for an incubation period before assessing citrullination.

23. The method of claim 22, wherein the incubating is performed at 35-40°C.

24. The method of claim 22 or 23, wherein the incubation period is 48 to 96 hours.

25. The method of any one of claims 1-24, comprising preparing the biological sample for assessment prior to the assessing.

26. The method of claim 25, wherein the preparing comprises enzymatically digesting proteins in the biological sample to form peptide fragments thereof.

27. The method of claim 25 or 26, wherein the preparing comprises depleting proteins or peptide fragments thereof from the biological sample that are not targeted by the assessing.

28. The method of any one of claims 25-27, wherein the preparing comprises diluting the biological sample.

29. The method of any one of claims 25-28, wherein the preparing comprises denaturing proteins or peptide fragments thereof in the biological sample.

30. The method of any one of claims 25-29, wherein the preparing comprises enriching the biological sample for a protein or peptide fragment thereof that comprises the citrullination site to be assessed.

31. The method of claim 30, wherein the preparing comprises contacting the biological sample with an antibody that specifically binds to citrullinated and noncitrullinated forms of the protein or peptide fragment thereof that comprises the citrullination site to be assessed.

32. The method of any one of claims 1-31, wherein the method comprises freezing and thawing the biological sample before assessing citrullination of the citrullination site.

33. The method of any one of claims 1-32, comprising:(a) immunoenriching the sample for the protein or peptide fragment thereof to form an immunoenriched sample, wherein the immunoenriching comprises contacting the sample with an antibody that binds to both citrullinated and noncitrullinated forms of the protein and / or to both citrullinated and noncitrullinated forms of the peptide fragment thereof comprising the citrullination site,(b) enzymatically digesting proteins in the sample either before or after the immunoenriching to form the peptide fragment, and(c) assessing citrullination of the peptide fragment at the citrullination site.

34. The method of claim 33, wherein the immunoenriching comprises contacting the sample with an immobilized antibody that binds to both citrullinated and noncitrullinated forms of the protein and / or to both citrullinated and noncitrullinated forms of the peptide fragment thereof comprising the citrullination site, and eluting protein and / or peptide bound to the immobilized antibody.

35. The method of claim 33 or 34, wherein the enzymatically digesting is conducted before the immunoenriching.

36. The method of claim 33 or 34, wherein the enzymatically digesting is conducted after the immunoenriching.

37. The method of any one of claims 33-36, wherein the immunoenriching comprises incubating the sample with the immobilized antibody for at least 30 minutes.

38. The method of claim 37, wherein the incubating is at a temperature of 22-28°C.

39. The method of claim 37 or 38, wherein the incubating is for a period of 30 to 90 minutes.

40. The method of any one of claims 33-38, wherein the immunoenriching comprises shaking during the incubating.

41. The method of any one of claims 34-40, wherein the immunoenriching comprises removing the immobilized antibody from the sample and washing the immobilized antibody prior to the eluting.

42. The method of any one of claims 34-41, wherein the eluting comprises washing the immobilized antibody with an elution composition under acidic conditions.

43. The method of claim 42, wherein the elution composition comprises a detergent.

44. The method of claim 43, wherein the detergent is a zwitterionic detergent.

45. The method of any one of claims 34-44, the method comprises neutralizing eluted protein in a buffer prior to assessing, and optionally prior to enzymatically digesting.

46. The method of any one of claims 33-45, wherein the antibody is immobilized by attachment to a solid surface.

47. The method of any one of claims 33-46, wherein the assessing citrullination comprises measuring a first concentration of citrullinated peptide in the digested peptides and a second concentration of signature peptide in the digested peptides, and optionally determining a citrullination ratio, wherein the citrullination ratio is a ratio of the first concentration to the second concentration.

48. The method of any one of claims 33-47, comprising denaturing proteins in the immunoenriched sample prior to the assessing.

49. The method of any one of claims 34-48, comprising denaturing the eluted protein prior to the assessing.

50. The method of claim 49, comprising denaturing the eluted protein prior to enzymatically digesting the eluted protein.

51. The method of any one of claims 33-50, comprising diluting the plasma or serum sample prior to the immunoenriching and performing the immunoenriching on the sample that has been diluted.

52. The method of claim 51, comprising diluting the plasma or serum sample by 2 to 1000 fold.

53. The method of claim 51 or 52, wherein the sample that has been diluted has a volume of at least 5 pl.

54. The method of any one of claims 1-53, wherein the sequence of the peptide fragment comprises one of the following sequences, wherein the citrullination site is designated by underlining: AITTRSGQTLSK (SEQ ID NO: 247), ESSSHHPGIAEFPSRGK (SEQ ID NO: 248), QFTSSTSYNRGDSTFESK (SEQ ID NO: 249), SGQSEDRQPVPGQQMTLK (SEQ ID NO: 250), ASHLGLARSNLDEDIIAEENIVSR (SEQ ID NO: 251), QLGLPGPPDVPDHAAYHPFRR (SEQ ID NO: 252), GPCRAFIQLWAFDAVK (SEQ ID NO: 253), VGFYESDVMGRGHAR (SEQ ID NO: 254), ATASRGASQAGAPQGR (SEQ ID NO: 255), LRTEGDGVYTLNDK (SEQ ID NO: 256), and DLLFRDDTVCLAK (SEQ ID NO: 257).

55. The method of any one of claims 1-54, wherein the biological sample comprises whole blood, plasma, serum, or blood supernatant.

56. The method of claim 55, wherein the citrullination site is: R1391 of proteoglycan 4 (corresponding to R1391 of Q92954), R573 of fibrinogen alpha chain (corresponding toR591 ofP02671 or R593 ofP02671.

57. The method of claim 56, wherein the peptide fragment comprises the amino acid sequence of AITTRSGQTLSK (SEQ ID NO: 247), ESSSHHPGIAEFPSRGK (SEQ ID NO: 248), or QFTSSTSYNRGDSTFESK (SEQ ID NO: 249), wherein the underlined R is the citrullination site.

58. The method of any one of claims 1-54, wherein the biological sample comprises synovial fluid.

59. The method of claim 58, wherein the citrullination site is: R1391 of proteoglycan 4 (corresponding to R1391 of Q92954), R573 of fibrinogen alpha chain (corresponding to R573 of P02671), R591 of fibrinogen alpha chain (corresponding to R591 of P02671), at R591 ofP02671 or R593 ofP02671, R573 of complement C3 (corresponding to R573 of P01024), R688 of inter-alpha-trypsin inhibitor heavy chain H4 (corresponding to R688 of QI 4624), or R297 of alpha- 1-microglobulin / bikunin precursor (corresponding to R297 of P02760).

60. The method of claim 59, wherein the sequence of the peptide fragment comprises one of the following sequences, wherein the citrullination site is designated by underlining: AITTRSGQTLSK (SEQ ID NO: 247), ESSSHHPGIAEFPSRGK (SEQ ID NO: 248), QFTSSTSYNRGDSTFESK (SEQ ID NO: 249), SGQSEDRQPVPGQQMTLK (SEQ ID NO: 250), QLGLPGPPDVPDHAAYHPFRR (SEQ ID NO: 252), and GPCRAFIQLWAFDAVK (SEQ ID NO: 253).

61. The method of any one of claims 1-60, wherein the method comprises assessing citrullination of two or more proteins or peptide fragments thereof.

62. The method of any one of claims 1-60, wherein the method further comprises assessing citrullination of at least one additional citrullination site listed in Table A or in any one of Tables 3-18.

63. A method comprising:(a) immunoenriching a biological sample for a protein of interest to form an immunoenriched sample, wherein the immunoenriching comprises contacting the sample with an antibody that specifically binds to both citrullinated and noncitrullinated forms of the protein of interest or that specifically binds to both citrullinated and noncitrullinated forms of a peptide fragment of the protein ofinterest, the protein of interest or peptide fragment comprising a citrullination site, and(b) assessing citrullination in the immunoenriched sample at the citrullination site.

64. A method comprising:(a) immunoenriching a biological sample for a protein of interest to form an immunoenriched sample, wherein the immunoenriching comprises contacting the sample with an antibody that binds to both citrullinated and noncitrullinated forms of the protein of interest or that specifically binds to both citrullinated and noncitrullinated forms of a peptide fragment of the protein of interest, the protein of interest or the peptide fragment comprising a citrullination site,(b) enzymatically digesting the immunoenriched sample to form peptide fragments of the protein of interest, wherein parts (a) and (b) may be performed in any order, and(c) assessing citrullination of the peptide fragments at the citrullination site.

65. A method comprising(a) immunoenriching a biological sample by contacting the sample with an immobilized antibody that binds to both citrullinated and noncitrullinated forms of a protein of interest, the protein of interest comprising a citrullination site,(b) eluting protein bound to the immobilized antibody,(d) enzymatically digesting the eluted protein to form peptide fragments thereof, and(e) assessing citrullination of the peptide fragments at the citrullination site.

66. A method comprising(a) enzymatically digesting proteins in a biological sample to form peptide fragments thereof,(b) immunoenriching the enzymatically digested biological sample by contacting the sample with an immobilized antibody that specifically binds to both citrullinated and noncitrullinated forms of a peptide fragment of a protein of interest, the peptide fragment comprising a citrullination site,(c) eluting peptides bound to the immobilized antibody, and(d) assessing citrullination of the peptides at the citrullination site.

67. The method of any one of claims 63-66, wherein the sample comprises whole blood, plasma, serum, or blood supernatant.

68. A method of assessing the activity of a PAD4 inhibitor, the method comprising(a) obtaining a biological sample from a subject following treatment of the subject with at least one dose of a PAD4 inhibitor, and(b) assessing citrullination of a citrullination site on a protein or a peptide fragment thereof that is present in the biological sample.

69. An in vitro method of assessing the activity of a PAD4 inhibitor, the method comprising(a) treating a biological sample from a subject with a PAD4 inhibitor to form a treated biological sample, and after the treating,(b) assessing citrullination of a citrullination site on a protein or a peptide fragment thereof that is present in the biological sample.

70. An in vitro method of assessing the activity of a PAD4 inhibitor, the method comprising(i) dividing a biological sample obtained from a subject into a plurality of biological samples,(ii) contacting each of the plurality of biological samples with a different dose of the PAD4 inhibitor, and(iii) assessing, for each of the plurality of biological samples, citrullination of a PAD4- dependent citrullination site on a protein or peptide fragment thereof that is present in the biological sample.

71. The method of claim 70, further comprising calculating an IC50 for the PAD4 inhibitor based on the outcome of the assessing.

72. The method of any one of claims 68 or 70-71, further comprising selecting or adjusting a dose of a PALM inhibitor to be administered to the subject based on the outcome of the assessing.

73. An in vitro method of assessing citrullination by endogenous PALM, the method comprising(a) incubating a whole blood sample from a subject at 35-40°C for an incubation period,(b) after the incubation period, separating plasma or supernatant from the whole blood sample, and(c) assessing citrullination of a citrullination site on a protein or peptide fragment thereof that is present in the plasma or supernatant.

74. An in vitro method of assessing changes in citrullination in a subject, the method comprising(a) incubating a whole blood sample from a subject at 35-40°C for an incubation period,wherein the sample is obtained from the subject following administration of a PAD4 inhibitor to the subj ect,(b) after the incubation period, separating plasma or supernatant from the whole blood sample, and(c) assessing citrullination of a citrullination site on a protein or peptide fragment thereof that is present in the plasma or supernatant.

75. The method of claim 74, further comprising(d) incubating a second whole blood sample from the subject at 35-40°C for an incubation period, wherein the second whole blood sample is obtained from the subject before administration of the PAD4 inhibitor to the subject,(e) after the incubation period, separating plasma or supernatant from the second whole blood sample, and(f) assessing citrullination of a citrullination site on a protein or peptide fragment thereof that is present in the plasma or supernatant from the second whole blood sample.

76. The method of claim 74, further comprising comparing an outcome of the assessing in step (f) with an outcome of the assessing in step (c).

77. A method of assessing effects of a PALM inhibitor, the method comprising(a) exposing a whole blood sample from a subject to a PALM inhibitor in vitro,(b) incubating the whole blood sample at 35-40°C for an incubation period,(c) after the incubation period, separating plasma or supernatant from the whole blood sample, and(d) assessing citrullination of a citrullination site on a protein or peptide fragment thereof that is present in the plasma or supernatant.

78. The method of claim 75, further comprising(e) incubating a control whole blood sample at 35-40°C for an incubation period,(f) after the incubation period, separating control plasma or supernatant from the control whole blood sample, and(g) assessing citrullination of a citrullination site on a protein or peptide fragment thereof that is present in the control plasma or supernatant.

79. The method of claim 78, further comprising comparing an outcome of the assessing in step (g) with an outcome of the assessing in step (d).

80. An in vitro method of assessing PAD4-dependent citrullination, the method comprising assessing citrullination of a citrullination site on a protein or peptide fragment thereof that is present in plasma or supernatant that has been separated from a whole blood sample that has been incubated at 35-40°C for an incubation period.

81. The method of claim 88, wherein the plasma or supernatant has been frozen and the method comprises thawing the plasma or supernatant prior to the assessing.

82. A method of assessing citrullination at a citrullination site, the method comprising(i) measuring a first concentration of a citrullinated protein or a citrullinated peptide in a biological sample by mass spectrometry (MS), wherein the citrullinated protein or citrullinated peptide is citrullinated at a citrullination site, and(ii) measuring a second concentration of corresponding total protein in the biological sample by MS.

83. The method of claim 82, wherein the method comprises (i) measuring a first concentration of a citrullinated peptide from a target protein in a biological sample by MS, wherein the citrullinated peptide is citrullinated at a citrullination site, and (ii) measuring the second concentration by measuring the concentration of a signature peptide from the target protein in the biological sample by MS.

84. The method of claim 82 or 83, further comprising calculating a ratio of the first concentration to the second concentration85. The method of any one of claims 82-84, wherein the method comprises measuring the first concentration and the second concentration for each of a plurality of different proteins or peptides.

86. The method of claim 85, wherein the method comprises measuring the first concentration for each of two different peptides, each of which are nonoverlapping fragments of the same protein and contain different citrullination sites.

87. The method of claim 85 or 86, wherein the method comprises calculating a ratio of the first concentration to the second concentration for each of the plurality of different proteins or peptides.

88. The method of any one of claims 63-87, wherein the citrullination site a site listed in Table A or in any one of Tables 3-18.

89. The method of any one of claims 63-88, wherein the citrullination site is selected from one or more of the following:R1391 of proteoglycan 4 (corresponding to R1391 of Q92954),R573 of fibrinogen alpha chain (corresponding to R573 of P02671), R591 of fibrinogen alpha chain (corresponding to R591 of P02671), R573 of complement C3 (corresponding to R573 of PO 1024), R748 of complement C3 (corresponding to R748 of PO 1024), R688 of inter-alpha-trypsin inhibitor heavy chain H4 (corresponding to R688 of QI 4624),R297 of alpha- 1-microglobulin / bikunin precursor (corresponding to R297 of P02760), R715 of alpha-2-macroglobulin (corresponding to R715 of PO 1023), R32 of gel solin (corresponding to R32 of P06396),R59 of haptoglobin (corresponding to R59 of P00738), and R651 of serotransferrin (corresponding to R651 ofP02787).

90. The method of claim 89, wherein the method comprises assessing citrullination at one of the following peptide sequences, wherein the citrullination site is designated by underlining: AITTRSGQTLSK (SEQ ID NO: 247), ESSSHHPGIAEFPSRGK (SEQ ID NO: 248), QFTSSTSYNRGDSTFESK (SEQ ID NO: 249), SGQSEDRQPVPGQQMTLK (SEQ ID NO: 250), ASHLGLARSNLDEDIIAEENIVSR (SEQ ID NO: 251), QLGLPGPPDVPDHAAYHPFRR (SEQ ID NO: 252), GPCRAFIQLWAFDAVK (SEQ ID NO: 253), VGFYESDVMGRGHAR (SEQ ID NO: 254), ATASRGASQAGAPQGR (SEQ ID NO: 255), LRTEGDGVYTLNDK (SEQ ID NO: 256), and DLLFRDDTVCLAK (SEQ ID NO: 257).

91. The method of any one of claims 1-90, wherein the biological sample is obtained from a subject that is ACPA positive.92 The method of any one of claims 1-91, wherein the biological sample is obtained from a subject that is positive for endogenous PAD4 antibodies.

93. The method of claim 92, wherein the subject is positive for endogenous PAD4 activating antibodies.

94. The method of any one of claims 1-93, wherein the biological sample is obtained from a subject that has been diagnosed with a citrullinati on-related disease or is at risk for developing a citrullination-related disease.

95. The method of any one of claims 1-94, wherein the method further comprises selecting the subject from which the biological sample was derived for treatment of a citrullinati on- related disease.

96. The method of claim 95, wherein the citrullination-related disease is an autoimmune disorder.

97. The method of claim 96, wherein the citrullination-related disease is rheumatoid arthritis, lupus (e.g., systemic lupus erythematosus (SLE)), lupus nephritis, vasculitis (e.g., ANCA- associated vasculitis), thrombosis (e.g, venous thrombosis), or inflammatory bowel disease (IBD) (e.g., ulcerative colitis, Crohn’s disease).

98. The method of any one of claims 1-97, wherein the biological sample is obtained from a subject following treatment of the subject with at least one dose of a PAD4 inhibitor.

99. The method of any one of claims 1-98, wherein the biological sample is obtained from a subject that is a normal, healthy subject.

100. The method of any one of claims 1-99, wherein the method further comprises administering a PAD4 inhibitor to the subject, and optionally assessing citrullinati on of a citrullinati on site on a protein or peptide fragment thereof in a sample from the subject collected following administering of the PAD4 inhibitor

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