Compositions and methods for treating inflammatory bowel disease

Abstract

Aspects of the disclosure provides composition and methods for treating a subject having inflammatory bowel disease, the method comprising administering to the subject a hemojuvelin (HIV) antagonist (e.g., anti-HJV antibody).

Description

COMPOSITIONS AND METHODS FOR TREATING INFLAMMATORY BOWELDISEASERELATED APPLICATIONS

[0001] This application claims the benefit under 35 U.S.C. § 119(e) of US Provisional Application No. 63 / 609,585, filed December 13, 2023, entitled “COMPOSITIONS AND METHODS FOR TREATING INFLAMMATORY BOWEL DISEASE” the content of which is hereby incorporated by reference herein in its entirety for all purposes.REFERENCE TO AN ELECTRONIC SEQUENCE LISTING

[0002] The contents of the electronic sequence listing (D084270013WO00-SEQ-LJG.xml; Size: 201,561 bytes; and Date of Creation: December 11, 2024) are herein incorporated by reference in its entirety.BACKGROUND

[0001] Inflammatory Bowel Disease (IBD) is characterized by repetitive episodes of inflammation of the gastrointestinal (GI) tract caused by an abnormal immune response associated with intestinal barrier dysfunction. IBD encompasses Ulcerative Colitis (UC) and Crohn’s Disease (CD), both of which can be classified by severity (mild, moderate, or severe). CD can also be classified by phenotype (inflammatory, stricturing, or penetrating). IBD can cause symptoms such as diarrhea, abdominal pain, rectal bleeding, weight loss, anemia, and fatigue, and can be associated with decreased quality of life (QoL). In some cases, IBD can lead to complications requiring hospitalization and / or surgery. Millions of individuals around the world are affected by IBD each year.SUMMARY

[0002] Certain aspects of the disclosure relate to a recognition that inhibiting hemojuvelin (HJV) in a subject that has barrier dysfunction (e.g., intestinal mucosal barrier dysfunction) reduces inflammation in the subjects. In some aspects, the present disclosure provides compositions (e.g., anti -HJV antibodies) and methods for treating a subject having inflammatory bowel disease (e.g., ulcerative colitis (UC), Crohn’s disease (CD), or IBD- unclassified (IBD-U)), the method comprising administering the subject a hemojuvelin antagonist (e.g., an anti-HJV antibody described herein). In some embodiments, methods and related compositions provided herein are useful for inhibiting inflammation (e.g., intestinal mucosal inflammation) in a subject having IBD. In some embodiments, composition andmethods provided herein can be used for purpose of reducing intestinal mucosal inflammation, reducing intestinal bleeding, improving clinical symptoms, inducing remission, and / or maintaining remission in a subject having IBD (e.g., UC, CD, or IBD-U).

[0003] In some aspects, provided herein are methods for inhibiting inflammation in a subject, the methods comprising administering an effective amount of an anti-hemojuvelin (HJV) antibody to the subject having inflammation associated with barrier dysfunction. In some embodiments, the barrier dysfunction is intestinal barrier dysfunction. In some embodiments, the subject has increased intestinal permeability relative to a subject that does not have intestinal barrier dysfunction. In some embodiments, the subject has intestinal mucosal barrier dysfunction. In some embodiments, the subject has an aberrant immune response to a gastrointestinal (GI) tract microbiome.

[0004] In some embodiments, the administration reduces systemic inflammation in the subject. In some embodiments, the administration reduces the number of circulating white blood cells in the subject. In some embodiments, the administration reduces the number of circulating neutrophils in the subject. In some embodiments, the administration reduces local inflammation at a site of the barrier dysfunction. In some embodiments, the administration reduces immune cell infiltration at the site of the barrier dysfunction. In some embodiments, the administration reduces neutrophil infiltration at the site of the barrier dysfunction. In some embodiments, the administration improves intestinal barrier function.

[0005] In some embodiments, the subject has ulcerative colitis.

[0006] In some embodiments, the subject has Crohn’s disease.

[0007] In some embodiments, the subject has IBD-unclassified.

[0008] In some aspects, provided herein are methods comprising administering an effective amount of an anti -HJV antibody to a subject having inflammation associated with inflammatory bowel disease (IBD).

[0009] In some aspects, provided herein are methods for treating inflammatory bowel disease (IBD) in a subject, the methods comprising administering an effective amount of an anti-HJV antibody to the subject, wherein the subject has inflammation associated with IBD.

[0010] In some aspects, provided herein are methods for treating a subject having active inflammatory bowel disease (IBD), the methods comprising administering an effective amount of an anti-HJV antibody to the subject.

[0011] In some aspects, provided herein are methods for treating a subject having chronic inflammatory bowel disease (IBD), the methods comprising administering an effective amount of an anti-HJV antibody to the subject.

[0012] In some aspects, provided herein are methods for treating inflammation in a subject having inflammatory bowel disease (IBD), the methods comprising administering an effective amount of an anti-HJV antibody to the subject.

[0013] In some embodiments, the subject has intestinal mucosal inflammation associated with IBD. In some embodiments, the subject has an aberrant immune response to a gastrointestinal (GI) tract microbiome. In some embodiments, the subject has acute phase IBD. In some embodiments, the subject has chronic phase IBD.

[0014] In some embodiments, the administration reduces systemic inflammation in the subject. In some embodiments, the administration reduces the number of circulating white blood cells. In some embodiments, the administration reduces the number of circulating neutrophils. In some embodiments, the administration reduces intestinal mucosal inflammation on a site of the barrier dysfunction. In some embodiments, the administration reduces immune cell infiltration in the intestine. In some embodiments, the administration reduces neutrophil infiltration in the intestine. In some embodiments, the administration inhibits the development of intestinal stricture.

[0015] In some embodiments, the subject is not responsive to or cannot tolerate treatment with one or more of aminosalicylates (5-ASA), corticosteroids, sphingosine 1 -phosphate receptor modulators, immunomodulators, Janus kinase (JAK) inhibitors, tumor necrosis factor (TNF) inhibitors, integrin antagonists, interleukin (IL)-23 antagonists, or IL- 12 antagonists.

[0016] In some embodiments, the subject has ulcerative colitis (UC). In some embodiments, the subject has mild to moderate active ulcerative colitis. In some embodiments, the subject has moderate to severe active ulcerative colitis. In some embodiments, the subject has severe active ulcerative colitis.

[0017] In some embodiments, the subject has a modified Mayo Disease Activity Index (MMDAI) score in the range of 3-12 prior to the administration. In some embodiments, the administration decreases the MMDAI score by at least 3 points.

[0018] In some embodiments, the subject has a Mayo endoscopic subscore (MES) of 1-3 prior to the administration. In some embodiments, the administration improves endoscopic appearance in the subject. In some embodiments, the administration decreases MES by at least 1 point.

[0019] In some embodiments, the administration induces endoscopic remission in the subject. In some embodiments, the administration maintains endoscopic remission in the subject. In some embodiments, the administration reduces stool frequency or bowelmovements. In some embodiments, the administration reduces rectal bleeding. In some embodiments, the administration induces clinical remission in the subject. In some embodiments, the administration maintains clinical remission in the subject. In some embodiments, the administration reduces the need for hospitalization due to severe uncreative colitis.

[0020] In some embodiments, the administration reduces extraintestinal symptoms of ulcerative colitis in the subject. In some embodiments, the extraintestinal symptom is fatigue.

[0021] In some embodiments, the subject has Crohn’s disease (CD). In some embodiments, the subject has a Crohn’s Disease Activity Index (CD Al) of at least 150 prior to the administration. In some embodiments, the subject has a CD Al in the range of 150-450 prior to the administration. In some embodiments, the subject has a CD Al more than 450 prior to the administration. In some embodiments, the administration reduces CD Al by at least 70. In some embodiments, the subject has one or more fistulas.

[0022] In some embodiments, the administration reduces the number of fistulas in the subject relative to the number of fistulas in the subject prior to the administration. In some embodiments, the administration maintains fistular closure in the subject. In some embodiments, the administration reduces the number of draining enterocutaneous fistulas in the subject. In some embodiments, the administration improves endoscopic appearance. In some embodiments, the administration promotes mucosal healing. In some embodiments, the administration reduces hospitalization of the subject. In some embodiments, the administration reduces the need for corticosteroids in the subject. In some embodiments, the administration induces clinical remission in the subject. In some embodiments, the administration maintains clinical remission in the subject. In some embodiments, the administration reduces fatigue in the subject.

[0023] In some aspects, provided herein are methods of treating ulcerative colitis (UC), the methods comprising administering an effective amount of an anti-HJV antibody to a subject having UC and experiencing mucosal inflammation. In some embodiments, the subject has acute phase UC. In some embodiments, the subject has chronic phase UC.

[0024] In some embodiments, the administration promotes mucosal healing in the subject. In some embodiments, the administration reduces shortening of colon in the subject. In some embodiments, the administration reduces weight loss in the subject. In some embodiments, the administration reduces stool frequency in the subject. In some embodiments, the administration reduces rectal bleeding in the subject. In some embodiments, the administration reduces systemic inflammation in the subject. In some embodiments, theadministration reduces the number of circulating white blood cells in the subject. In some embodiments, the administration reduces the number of circulating neutrophils in the subject. In some embodiments, the administration increases circulating red blood cell levels in the subject. In some embodiments, the administration increases hemoglobin in the subject. In some embodiments, the administration increases mean corpuscular hemoglobin (MCH) in the subject. In some embodiments, the administration increases transferrin saturation (TSAT%) in the subject. In some embodiments, the administration increases serum iron in the subject.

[0025] In some embodiments, the anti-HJV antibody is administered in combination with one or more of aminosalicylates (5-ASA), corticosteroids, sphingosine 1 -phosphate receptor modulators, immunomodulators, Janus kinase (JAK) inhibitors, tumor necrosis factor (TNF) inhibitors, integrin antagonists, interleukin (IL)-23 antagonists, or IL-12 antagonists. In some embodiments, the anti-HJV antibody is administered intravenously or subcutaneously.

[0026] In some embodiments, antibody comprises a heavy chain complementarity determining region (CDR) 1 (HC CDR1) comprising the amino acid of SEQ ID NO: 1, a HC CDR2 comprising the amino acid of SEQ ID NO: 2, a HC CDR3 comprising the amino acid of SEQ ID NO: 3; a light chain (LC) CDR1 comprising the amino acid of SEQ ID NO: 17, a LC CDR2 comprising the amino acid of SEQ ID NO: 5, and a LC CDR3 comprising the amino acid of SEQ ID NO: 27.

[0027] In some embodiments, the anti-HJV antibody comprises a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 38, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 39.

[0028] In some embodiments, the anti-HJV antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 61, and a light chain comprising the amino acid sequence of SEQ ID NO: 62.

[0029] In some embodiments, the anti-HJV antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 63, and a light chain comprising the amino acid sequence of SEQ ID NO: 62.BRIEF DESCRIPTION OF THE DRAWINGS

[0030] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate certain embodiments, and together with the written description, serve to provide non-limiting examples of certain aspects of the compositions and methods disclosed herein.

[0031] FIGs. 1A-1C demonstrate that anti-hemojuvelin (HJV) antibody treatment reducesseverity of dextran sulfate sodium (DSS)-induced ulcerative colitis. FIG. 1A shows the weight of mice in Groups 1-6 over the course of the DSS study. Anti-HJV antibody treatment ameliorated DSS-induced weight loss (*p < 0.05, **p < 0.01, ***p < 0.001 vs 4 cycles of DSS) FIG. IB shows the colon length of mice in Groups 1-6 at the defined endpoint for each group (Group 1 : day 0; Group 2: day 6; Group 3: day 13; Group 4: day 20; Group 5: day 27; Group 6: day 27). Anti-HJV antibody treatment ameliorated DSS-induced colon stricturing (**p < 0.01, ***p < 0.001 vs 4 cycles of DSS). FIG. 1C shows the disease activity index (DAI) score of mice in Groups 1-6 over the course of the DSS study. Anti-HJV antibody treatment improved DSS-induced disease severity (**p < 0.01, ***p < 0.001 vs 4 cycles of DSS).

[0032] FIGs. 2A-2H demonstrate improvement of blood cell counts and inflammation in DSS-induced colitis with administration of anti-HJV antibody. FIGs. 2A-2C show improved erythroid parameters, including red blood cell (RBC) count (FIG. 2A), hemoglobin (HGB) (FIG. 2B), and mean corpuscular hemoglobin (MCH) (FIG. 2C), in DSS-treated mice when treated with anti-HJV. Anti-HJV improved anemia in the DSS-induced colitis mouse model (**p < 0.01 vs 4 cycles of DSS). FIGs. 2D-2E show anti-HJV treatment increased serum iron levels (FIG. 2D) and transferrin saturation (TSAT%) (FIG. 2E) in DSS-treated mice. Treatment of anti-HJV restored both serum iron levels and TSAT% to normal (*p < 0.05 **p < 0.01 vs 4 cycles of DSS). FIGs. 2F-2H show that anti-HJV antibody treatment attenuated systemic inflammation in the DSS-induced colitis mouse model. Comparison between Group 5 and Group 6 showed a decrease in circulating levels of white blood cells (WBCs) (FIG.2F) and neutrophils (FIG. 2G) in mice treated with anti-HJV antibody (*p < 0.05**p < 0.01 vs 4 cycles of DSS). Additionally, there was a trend for lower lymphocyte count in the anti- HJV-treated group (Group 6) (p = 0.11 vs Group 5). Surprisingly, these data demonstrate that HJV antagonism dampened the inflammatory response by decreasing systemic WBC and neutrophil counts.DETAILED DESCRIPTION

[0033] According to some aspects, the disclosure provides compositions and methods for treating a subject having IBD, the method comprising administering to the subject a hemojuvelin (HJV) antagonist (e.g., anti-HJV antibody). In some embodiments, the disclosure provides compositions and methods for treating a subject having ulcerative colitis (UC), the method comprising administering to the subject a hemojuvelin (HJV) antagonist (e.g., anti-HJV antibody). In some embodiments, the disclosure provides compositions andmethods for treating a subject having Crohn’s Disease (CD), the method comprising administering to the subject a hemojuvelin (HJV) antagonist (e.g., anti-HJV antibody). In some embodiments, the disclosure provides compositions and methods for treating a subject having IBD-unclassified (IBD-U) the method comprising administering to the subject a hemojuvelin (HJV) antagonist (e.g., anti-HJV antibody).

[0034] Further aspects of the disclosure, including a description of defined terms, are provided below.I. Definitions

[0035] Administering: As used herein, the terms “administering” or “administration” means to provide a complex to a subject in a manner that is physiologically and / or pharmacologically useful (e.g., to treat a condition in the subject).

[0036] Antibody: As used herein, the term “antibody” refers to a polypeptide that includes at least one immunoglobulin variable domain or at least one antigenic determinant, e.g., paratope that specifically binds to an antigen. In some embodiments, an antibody is a full- length antibody. In some embodiments, an antibody is a chimeric antibody. In some embodiments, an antibody is a humanized antibody. However, in some embodiments, an antibody is a Fab fragment, a F(ab')2 fragment, a Fv fragment or a scFv fragment. In some embodiments, an antibody is a nanobody derived from a camelid antibody or a nanobody derived from shark antibody. In some embodiments, an antibody is a diabody. In some embodiments, an antibody comprises a framework having a human germline sequence. In another embodiment, an antibody comprises a heavy chain constant domain selected from the group consisting of IgG, IgGl, IgG2, IgG2A, IgG2B, IgG2C, IgG3, IgG4, IgAl, IgA2, IgD, IgM, and IgE constant domains. In some embodiments, an antibody comprises a heavy (H) chain variable region (abbreviated herein as VH), and / or a light (L) chain variable region (abbreviated herein as VL). In some embodiments, an antibody comprises a constant domain, e.g., an Fc region. An immunoglobulin constant domain refers to a heavy or light chain constant domain. Human IgG heavy chain and light chain constant domain amino acid sequences and their functional variations are known. With respect to the heavy chain, in some embodiments, the heavy chain of an antibody described herein can be an alpha (a), delta (A), epsilon (s), gamma (y) or mu (p) heavy chain. In some embodiments, the heavy chain of an antibody described herein can comprise a human alpha (a), delta (A), epsilon (s), gamma (y) or mu (p) heavy chain. In a particular embodiment, an antibody described herein comprises a human gamma 1 CHI, CH2, and / or CH3 domain. In some embodiments, the amino acidsequence of the VH domain comprises the amino acid sequence of a human gamma (y) heavy chain constant region, such as any known in the art. Non-limiting examples of human constant region sequences have been described in the art, e.g., see U.S. Pat. No. 5,693,780 and Kabat E A et al., (1991) supra. In some embodiments, the VH domain comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, or at least 99% identical to any of the variable chain constant regions provided herein. In some embodiments, an antibody is modified, e.g., modified via glycosylation, phosphorylation, sumoylation, and / or methylation. In some embodiments, an antibody is a glycosylated antibody, which is conjugated to one or more sugar or carbohydrate molecules. In some embodiments, the one or more sugar or carbohydrate molecule are conjugated to the antibody via N-glycosylation, O- glycosylation, C-glycosylation, glypiation (GPI anchor attachment), and / or phosphoglycosylation. In some embodiments, the one or more sugar or carbohydrate molecule are monosaccharides, disaccharides, oligosaccharides, or glycans. In some embodiments, the one or more sugar or carbohydrate molecule is a branched oligosaccharide or a branched glycan. In some embodiments, the one or more sugar or carbohydrate molecule includes a mannose unit, a glucose unit, an N-acetylglucosamine unit, or a phospholipid unit. In some embodiments, an antibody is a construct that comprises a polypeptide comprising one or more antigen binding fragments of the disclosure linked to a linker polypeptide or an immunoglobulin constant domain. Linker polypeptides comprise two or more amino acid residues joined by peptide bonds and are used to link one or more antigen binding portions. Examples of linker polypeptides have been reported (see e.g., Holliger, P., et al. (1993) Proc. Natl. Acad. Set. USA 90:6444-6448; Poljak, R. J., et al. (1994) Structure 2: 1121-1123). Still further, an antibody may be part of a larger immunoadhesion molecule, formed by covalent or noncovalent association of the antibody or antibody portion with one or more other proteins or peptides. Examples of such immunoadhesion molecules include use of the streptavidin core region to make a tetrameric scFv molecule (Kipriyanov, S. M., et al. (1995) Human Antibodies and Hybridomas 6:93-101) and use of a cysteine residue, a marker peptide and a C-terminal polyhistidine tag to make bivalent and biotinylated scFv molecules (Kipriyanov, S. M., et al. (1994) Mol. Immunol. 31 : 1047-1058).

[0037] Affinity Matured Antibody: “Affinity Matured Antibody” is used herein to refer to an antibody with one or more alterations in one or more CDRs, which result in an improvement in the affinity (i.e., KD, kd or ka) of the antibody for a target antigen compared to a parent antibody, which does not possess the alteration(s). Exemplary affinity matured antibodies will have nanomolar or even picomolar affinities for the target antigen. A varietyof procedures for producing affinity matured antibodies are known in the art, including the screening of a combinatory antibody library that has been prepared using bio-display. For example, Marks et al., BioTechnology, 10: 779-783 (1992) describes affinity maturation by VH and VL domain shuffling. Random mutagenesis of CDR and / or framework residues is described by Barbas et al, Proc. Nat. Acad. Sci. USA, 91 : 3809-3813 (1994); Schier etal., Gene, 169: 147-155 (1995); Yelton et al., J. Immunol., 155: 1994-2004 (1995); Jackson et al., J. Immunol., 154(7): 3310-3319 (1995); and Hawkins et al., J. Mol. Biol., 226: 889-896 (1992). Selective mutation at selective mutagenesis positions and at contact or hypermutation positions with an activity-enhancing amino acid residue is described in U.S. Pat. No. 6,914,128 Bl.

[0038] Approximately: As used herein, the term “approximately” or “about,” as applied to one or more values of interest, refers to a value that is similar to a stated reference value. In certain embodiments, the term “approximately” or “about” refers to a range of values that fall within 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, or less in either direction (greater than or less than) of the stated reference value unless otherwise stated or otherwise evident from the context (except where such number would exceed 100% of a possible value).

[0039] Baseline level: As used herein, the term “baseline level” refers to a value that represents the beginning level (including normal or diseased level) of a measurable quality, used for comparison with values representing response to an intervention (e.g., a drug, a medical procedural, or a control). In some embodiments, the baseline reflects the health state — disease severity, confounding conditions, biomarkers (e.g., hematological biomarkers) — present in a person or group of individuals at the beginning of a process. In some embodiments, the process is a medical treatment plan. In some embodiments, the process is a prospective study (e.g., clinical trial). In some embodiments, the baseline value is the last non-missing value before a subject starts the process (e.g., treatment plan or clinical trial). In some embodiments, the baseline value is the value before a subject suffers a condition (e.g., a condition associated with barrier dysfunction (e.g., IBD, UC, or CD) described herein. In some embodiments, the subject experiences a change in values compared to the baseline value prior to receiving the drug, and treatment using the drug brings the values back to baseline levels. In some embodiments, treatment of a drug brings the values back to baseline levels more rapidly compared to a subject who did not receive the drug.

[0040] Comorbidity: As used herein, a “comorbidity” refers to one or more conditions or disorders that co-occur with (or are coincident with) a primary condition (such as a diseaseassociated with barrier dysfunction (e.g., IBD, UC, or CD) in an individual.

[0041] Control subject: A subject that has comparable features and property as the subject, e.g., age, species, state of health, and other similar parameters. In some embodiments, control subject may be a group of subjects having a similar condition (e.g., IBD) but is receiving, or is expected to receive a different treatment from the therapy described herein (e.g., treatment using an hemojuvelin antagonist). In some embodiments, in an experiment or clinical trial, control subjects may be a group of participants who have characteristics similar to those of the treatment group, but they do not receive the treatment being studied. In some embodiments, the control subjects receive a substance or treatment which is designed to have no therapeutic value (i.e., a placebo).

[0042] CDR: As used herein, the term "CDR" refers to the complementarity determining region within antibody variable sequences. Atypical antibody molecule comprises a heavy chain variable region (VH) and a light chain variable region (VL), which are usually involved in antigen binding. The VH and VL regions can be further subdivided into regions of hypervariability, also known as “complementarity determining regions” (“CDR”), interspersed with regions that are more conserved, which are known as “framework regions” (“FR”). Each VH and VL is typically composed of three CDRs and four FRs, arranged from amino-terminus to carboxy -terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. The extent of the framework region and CDRs can be precisely identified using methodology known in the art, for example, by the Kabat definition, the IMGT definition, the Chothia definition, the AbM definition, and / or the contact definition, all of which are well known in the art. See, e.g., Kabat, E.A., etal., (1991) Sequences of Proteins of Immunological Interest, Fifth Edition, U.S. Department of Health and Human Services, NTH Publication No. 91-3242; IMGT®, the international ImMunoGeneTics information system® http: / / www.imgt.org, Lefranc, M.-P. et cd., Nucleic Acids Res., 27:209-212 (1999); Ruiz, M. et al., Nucleic Acids Res., 28:219-221 (2000); Lefranc, M.-P, Nucleic Acids Res., 29:207-209 (2001); Lefranc, M.-P, Nucleic Acids Res., 31 :307-310 (2003); Lefranc, M.-P. et al., In Silica Biol., 5, 0006 (2004) [Epub], 5:45-60 (2005); Lefranc, M.-P. et al., Nucleic Acids Res., 33:D593-597 (2005); Lefranc, M.-P. et al., Nucleic Acids Res., 37:D1006-1012 (2009);Lefranc, M.-P. et al., Nucleic Acids Res., 43:D413-422 (2015); Chothia et al., (1989) Nature 342:877; Chothia, C. et al., (1987) J. Mol. Biol. 196:901-917, Al-lazikani et al., (1997) J. Molec. Biol. 273:927-948; and Almagro, J. Mol. Recognit. 17: 132-143 (2004). See also: hgmp.mrc.ac.uk and bioinf.org.uk / abs. As used herein, a CDR may refer to the CDR defined by any method known in the art. Two antibodies having the same CDR means that the twoantibodies have the same amino acid sequence of that CDR as determined by the same method, for example, the IMGT definition.

[0043] Generally, there are three CDRs in each of the variable regions of the heavy chain and the light chain, which are designated CDR1, CDR2 and CDR3, for each of the variable regions. The term "CDR set" as used herein refers to a group of three CDRs that occur in a single variable region capable of binding the antigen. The exact boundaries of these CDRs have been defined differently according to different systems. The system described by Kabat (Kabat et al., Sequences of Proteins of Immunological Interest (National Institutes of Health, Bethesda, Md. (1987) and (1991)) not only provides an unambiguous residue numbering system applicable to any variable region of an antibody, but also provides precise residue boundaries defining the three CDRs. These CDRs may be referred to as Kabat CDRs. Subportions of CDRs may be designated as LI, L2 and L3 or Hl, H2 and H3 where the "L" and the "H" designates the light chain and the heavy chains regions, respectively. These regions may be referred to as Chothia CDRs, which have boundaries that overlap with Kabat CDRs. Other boundaries defining CDRs overlapping with the Kabat CDRs have been described by Padlan (FASEB J. 9: 133-139 (1995)) and MacCallum (J Mol Biol 262(5):732-45 (1996)). Still other CDR boundary definitions may not strictly follow one of the above systems, but will nonetheless overlap with the Kabat CDRs, although they may be shortened or lengthened in light of prediction or experimental findings that particular residues or groups of residues or even entire CDRs do not significantly impact antigen binding. The methods used herein may utilize CDRs defined according to any of these systems, although exemplary embodiments use Kabat or Chothia defined CDRs.

[0044] CDR-grafted antibody: The term "CDR-grafted antibody" refers to antibodies which comprise heavy and light chain variable region sequences from one species but in which the sequences of one or more of the CDR regions of VH and / or VL are replaced with CDR sequences of another species, such as antibodies having murine heavy and light chain variable regions in which one or more of the murine CDRs ( e.g., CDR3) has been replaced with human CDR sequences.

[0045] Chimeric antibody: The term "chimeric antibody" refers to antibodies which comprise heavy and light chain variable region sequences from one species and constant region sequences from another species, such as antibodies having murine heavy and light chain variable regions linked to human constant regions.

[0046] Complementary: As used herein, the term “complementary” refers to the capacity for precise pairing between two nucleotides or two sets of nucleotides. In particular,complementary is a term that characterizes an extent of hydrogen bond pairing that brings about binding between two nucleotides or two sets of nucleotides. For example, if a base at one position of an oligonucleotide is capable of hydrogen bonding with a base at the corresponding position of a target nucleic acid (e.g., an mRNA), then the bases are considered to be complementary to each other at that position. Base pairings may include both canonical Watson-Crick base pairing and non-Watson-Crick base pairing (e.g., Wobble base pairing and Hoogsteen base pairing). For example, in some embodiments, for complementary base pairings, adenosine-type bases (A) are complementary to thymidine- type bases (T) or uracil-type bases (U), that cytosine-type bases (C) are complementary to guanosine-type bases (G), and that universal bases such as 3 -nitropyrrole or 5-nitroindole can hybridize to and are considered complementary to any A, C, U, or T. Inosine (I) has also been considered in the art to be a universal base and is considered complementary to any A, C, U or T.

[0047] Conservative amino acid substitution: As used herein, a “conservative amino acid substitution” refers to an amino acid substitution that does not alter the relative charge or size characteristics of the protein in which the amino acid substitution is made. Variants can be prepared according to methods for altering polypeptide sequence known to one of ordinary skill in the art such as are found in references which compile such methods, e.g. Molecular Cloning: A Laboratory Manual, J. Sambrook, et cd.. eds., Fourth Edition, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, 2012, or Current Protocols in Molecular Biology, F.M. Ausubel, et al., eds., John Wiley & Sons, Inc., New York. Conservative substitutions of amino acids include substitutions made amongst amino acids within the following groups: (a) M, I, L, V; (b) F, Y, W; (c) K, R, H; (d) A, G; (e) S, T; (f) Q, N; and (g) E, D.

[0048] Cross-reactive: As used herein and in the context of a targeting agent (e.g., antibody), the term “cross-reactive,” refers to a property of the agent being capable of specifically binding to more than one antigen of a similar type or class (e.g., antigens of multiple homologs, paralogs, or orthologs) with similar affinity or avidity. For example, in some embodiments, an antibody that is cross-reactive against human and non-human primate antigens of a similar type or class (e.g., a human hemojuvelin and non-human primate hemojuvelin) is capable of binding to the human antigen and non-human primate antigens with a similar affinity or avidity. In some embodiments, an antibody is cross-reactive against a human antigen and a rodent antigen of a similar type or class. In some embodiments, an antibody is cross-reactive against a rodent antigen and a non-human primate antigen of asimilar type or class. In some embodiments, an antibody is cross-reactive against a human antigen, a non-human primate antigen, and a rodent antigen of a similar type or class.

[0049] Effective Amount: As used herein, “an effective amount” or “an amount effective” refers to the amount of each active agent (e.g., hemojuvelin antagonist including an anti-HJV antibody) required to confer therapeutic effect on the subject (such as in treating a condition associated with barrier dysfunction (e.g., IBD), either alone or in combination with one or more other active agents).

[0050] Erythropoiesis: As used herein, the term “erythropoiesis” refers to the process of producing red blood cells (RBCs or erythrocytes). In some embodiments, erythropoiesis comprises development from hematopoietic stem cells to mature red blood cells. For example, in the process of red blood maturation, a cell generally undergoes a series of differentiation steps, which may include, in the bone marrow, hemocytoblasts (a multipotent hematopoietic stem cells) differentiating along a path comprising one or more of common myeloid progenitors, unipotent stem cells, proerythroblasts, erythroblasts, polychromatophilic cells, and orthochromatic cells. In some embodiments, nuclear expulsion occurs at the end of the orthochromatic stage through an asymmetric division of the orthochromatic erythroblast, becoming a reticulocyte, which is an immature red blood cell. The reticulocytes are generally released from the bone marrow into the circulation, and ultimately become "erythrocytes" or mature red blood cells one or two days later. Therefore, reticulocytes are primarily present in circulating blood. In some embodiments, by the reticulocyte stage, the cell has extruded its nucleus, but is still capable of producing hemoglobin. In further embodiments, normal RBC count in a subject is in the range of 4.7xl012to 6.1xl012cells / L in men or 4.2xl012to 5.4xl012cells / L.

[0051] Ferritin: As used herein, the term “ferritin” refers to a protein that stores iron and releases it in a controlled fashion. It is the primary intracellular iron-storage protein in both prokaryotes and eukaryotes, keeping iron in a soluble and non-toxic form. In humans, it acts as a buffer against iron deficiency and iron overload. Circulating ferritin is also an indirect marker of the total amount of iron stored in the body; hence, serum ferritin is used as a diagnostic test for iron-deficiency anemia.

[0052] Framework: As used herein, the term "framework" or "framework sequence" refers to the remaining sequences of a variable region minus the CDRs. Because the exact definition of a CDR sequence can be determined by different systems, the meaning of a framework sequence is subject to correspondingly different interpretations. The six CDRs (CDR-L1, CDR-L2, and CDR-L3 of light chain and CDR-H1, CDR-H2, and CDR-H3 of heavy chain)also divide the framework regions on the light chain and the heavy chain into four subregions (FR1, FR2, FR3 and FR4) on each chain, in which CDR1 is positioned between FR1 and FR2, CDR2 between FR2 and FR3, and CDR3 between FR3 and FR4. Without specifying the particular sub-regions as FR1, FR2, FR3 or FR4, a framework region, as referred by others, represents the combined FRs within the variable region of a single, naturally occurring immunoglobulin chain. As used herein, a FR represents one of the four sub-regions, and FRs represents two or more of the four sub-regions constituting a framework region. Human heavy chain and light chain acceptor sequences are known in the art. In one embodiment, the acceptor sequences known in the art may be used in the antibodies disclosed herein.

[0053] Hemojuvelin (HJV): As used herein, the term “hemojuvelin (HJV)” (also known as repulsive guidance molecule C (RGMc) or hemochromatosis type 2 protein (HFE2)) refers to a membrane-bound and soluble form protein that regulates hepcidin production through the bone morphogenic protein (BMP) / SMAD signaling pathway (Xiao et al., “Bone morphogenic proteins in iron homeostasis.” Bone. 2020; 138: 115495). The HFE2 gene encodes two known classes of glycosylphosphatidylinositol (GPI)-anchored and glycosylated HJV molecules, which are targeted to the membrane and undergo distinct fates. HJV exists in multiple isoforms, including two soluble isoforms and two membrane-associated isoforms. In some embodiments, a predominant membrane-associated isoform is a disulfide-linked two- chain form composed of N- and C-terminal fragments. In some embodiments, a full-length single-chain isoform associates with the membrane, but is released from the cell surface and accumulates in extracellular fluid. In some embodiments, HJV may be of human (NCBI Gene ID 148738), non-human primate (e.g., NCBI Gene ID 698805), or rodent (e.g., NCBI Gene ID 69585 or NCBI Gene ID 310681) origin. In addition to HJV (RGMc), the repulsive guidance molecule family includes repulsive guidance molecule A (RGMa) and repulsive guidance molecule B (RGMb). RGMa and RGMb are expressed in the central nervous system during development and are thought to be involved in controlling axonal patterning and neuronal survival, while HJV is produced in the liver and in cardiac and skeletal muscle.

[0054] Hepcidin: As used herein, a “hepcidin” refers to an iron-regulating peptide hormone primarily made in the liver that is encoded by the HAMP gene. In some embodiments, hepcidin controls the delivery of iron to blood plasma from intestinal cells absorbing iron, from erythrocyte-recycling macrophages, and from iron-storing hepatocytes. Normal hepcidin levels vary depending on the measurement technique, gender, tissue, or fluid in which it is measured, and / or menopausal status. In some embodiments, hepcidininhibits iron transport by binding to the iron export channel ferroportin which is located on the basolateral surface of gut enterocytes and the plasma membrane of reticuloendothelial cells (macrophages). In some embodiments, inhibiting ferroportin prevents iron from being exported and the iron is sequestered in the cells. In some embodiments, by inhibiting ferroportin, hepcidin prevents enterocytes from allowing iron into the hepatic portal system, thereby reducing dietary iron absorption. Hepcidin expression involves multiple aspects, including, for example, transcription of the HAMP gene, translation of the transcribed mRNA, and the posttranslational processing of the hepcidin precursor into the bioactive hepcidin-25 peptide (DTHFPICIFCCGCCHRSKCGMCCKT (SEQ ID NO: 129)). In some embodiments, hepcidin expression is modulated via the hemojuvelin-induced BMP signaling pathway. In some embodiments, hepcidin expression is modulated via the IL-6-JAK-STAT signaling pathway.

[0055] Hepcidin Antagonist: As used herein, a “hepcidin antagonist” refers to an agent that reduces hepcidin expression and / or hepcidin activity (directly or indirectly). In some embodiments, a hepcidin antagonist inhibits hepcidin-induced ferroportin degradation. Accordingly, in some embodiments, a hepcidin antagonist targets hepcidin function indirectly through the hepcidin stimulatory pathway to decrease hepcidin expression. In some embodiments, a hepcidin antagonist targets hepcidin function directly, e.g., by binding the hepcidin peptide to sequester free hepcidin or by binding ferroportin to inhibit the hepcidin- ferroportin binding interaction, thereby decreasing hepcidin-induced ferroportin degradation. In some embodiments, a hepcidin antagonist is a ferroportin inhibitor that disrupts ferroportin-hepcidin interactions, such as, for example, as disclosed in Ross SL, etal., Identification of Antibody and Small Molecule Antagonists of Ferroportin-Hepcidin Interaction. Front Pharmacol. 2017 Nov 21 ;8 : 838; Fung E., et al., High-Throughput Screening of Small Molecules Identifies Hepcidin Antagonists. Molecular Pharmacology, March 2013, 83 (3) 681-690; and Angeliki Katsarou and Kostas Pantopoulos, Hepcidin Therapeutics. Pharmaceuticals (Basel). 2018 Dec; 11(4): 127, the relevant contents of each of which are incorporated herein by reference.

[0056] Hematological recovery: As used herein, the term “hematological recovery,” refers to a process of bringing the oxygen carrying capacity in the blood of a subject to a state that is comparable to (e.g., equal to or in the range of) baseline values of a normal, healthy subject (e.g., a normal, healthy control subject). A “typical” range for baseline oxygen levels in the blood of a normal, healthy subject is between 95% and 100% oxygen saturation. In some embodiments, hematological recovery may be assessed by evaluating levels of one or more oferythropoiesis, circulating hemoglobin levels, reticulocyte hemoglobin (CHr), and mean corpuscular hemoglobin (MCH), levels of which are indicative of whether a subject has achieved a homeostatic oxygen carrying capacity.

[0057] Hemoglobin: As used herein, the term “hemoglobin (Hgb)” refers to is the iron- containing oxygen-transport metalloprotein in red blood cells (erythrocytes). Hemoglobin in blood carries oxygen from the respiratory organs (e.g., lungs or gills) to the rest of the body (e.g., tissues). There it releases the oxygen to permit aerobic respiration to provide energy to power functions of an organism in the process called metabolism. A healthy individual human has about 12 to 20 g / dL of hemoglobin in blood. Hemoglobin (Hgb) is synthesized in a complex series of steps. The heme part is synthesized in a series of steps in the mitochondria and the cytosol of immature red blood cells, while the globin protein parts are synthesized by ribosomes in the cytosol. Iron is an essential element for hemoglobin synthesis, particularly heme synthesis. The final step of heme synthesis is the addition of an iron ion to protoporphyrin IX (PPIX), a precursor of heme, by ferrochelatase, thereby producing a heme molecule. Globin chain production occurs in the cytosol of erythrocytes and occurs by genetic transcription and translation. Many studies have shown that the presence of heme induces globin production. Heme combines with globin to form hemoglobin.

[0058] Human antibody: The term "human antibody", as used herein, is intended to include antibodies having variable and constant regions derived from human germline immunoglobulin sequences. The human antibodies of the disclosure may include amino acid residues not encoded by human germline immunoglobulin sequences (e.g., mutations introduced by random or site-specific mutagenesis in vitro or by somatic mutation in vivo), for example in the CDRs and in particular CDR3. However, the term "human antibody", as used herein, is not intended to include antibodies in which CDR sequences derived from the germline of another mammalian species, such as a mouse, have been grafted onto human framework sequences (e.g., CDRs grafted in a heterologous framework).

[0059] Humanized antibody: The term "humanized antibody" refers to antibodies which comprise heavy and light chain variable region sequences from a non-human species (e.g., a mouse) but in which at least a portion of the VH and / or VL sequence has been altered to be more "human-like", i.e., more similar to human germline variable sequences. One type of humanized antibody is a CDR-grafted antibody, in which human CDR sequences are introduced into non-human VH and VL sequences to replace the corresponding nonhuman CDR sequences. In one embodiment, humanized anti-hem ojuvelin antibodies and antigenbinding portions are provided. Such antibodies may be generated by obtaining murine anti- hemojuvelin monoclonal antibodies using traditional hybridoma technology followed by humanization using in vitro genetic engineering, such as those disclosed in Kasaian, et al. PCT publication No. WO 2005 / 123126 A2.

[0060] Isolated antibody: An "isolated antibody", as used herein, is intended to refer to an antibody that is substantially free of other antibodies having different antigenic specificities (e.g., an isolated antibody that specifically binds hemojuvelin is substantially free of antibodies that specifically bind antigens other than hemojuvelin). An isolated antibody that specifically binds hemojuvelin may, however, have cross-reactivity to other antigens, such as other repulsive guidance molecule (RGM) proteins (e.g., RGMa and / or RGMb). Moreover, an isolated antibody may be substantially free of other cellular material and / or chemicals.

[0061] Kabat numbering: The terms "Kabat numbering", "Kabat definitions and "Kabat labeling" are used interchangeably herein. These terms, which are recognized in the art, refer to a system of numbering amino acid residues which are more variable (i.e. hypervariable) than other amino acid residues in the heavy and light chain variable regions of an antibody, or an antigen binding portion thereof (Kabat, et al. (1971) Ann. NY Acad, Sci. 190:382-391 and, Kabat, E. A., et al. (1991) Sequences of Proteins of Immunological Interest, Fifth Edition, U.S. Department of Health and Human Services, NIH Publication No. 91-3242). For the heavy chain variable region, the hypervariable region ranges from amino acid positions 31 to 35 for CDR1, amino acid positions 50 to 65 for CDR2, and amino acid positions 95 to 102 for CDR3. For the light chain variable region, the hypervariable region ranges from amino acid positions 24 to 34 for CDR1, amino acid positions 50 to 56 for CDR2, and amino acid positions 89 to 97 for CDR3.

[0062] Mean corpuscular hemoglobin (MCH): As used herein, the term “mean corpuscular hemoglobin” refers to the average mass of hemoglobin (Hgb) per red blood cell (RBC) in a sample of blood. It is calculated by dividing the total mass of hemoglobin by the number of red blood cells in a volume of blood: MCH=(Hgb*10) / RBC.

[0063] In some embodiments, a normal MCH value in humans is 27 to 31 picograms (pg) / cell. The amount of hemoglobin per RBC depends on hemoglobin synthesis and the size of the RBC. The mass of the red cell is determined by the iron (as part of the hemoglobin molecule), thus MCH in picograms is roughly the mass of one red cell. In some embodiments, in iron deficiency anemia the cell mass becomes lighter, and a MCH below 27 pg is an indication of iron deficiency.

[0064] Recombinant antibody: The term "recombinant human antibody", as used herein, is intended to include all human antibodies that are prepared, expressed, created or isolated by recombinant means, such as antibodies expressed using a recombinant expression vector transfected into a host cell (described in more details in this disclosure), antibodies isolated from a recombinant, combinatorial human antibody library (Hoogenboom H. R., (1997) TIB Tech. 15:62-70; Azzazy H., and Highsmith W. E., (2002) Clin. Biochem. 35:425-445; Gavilondo J. V., and Larrick J. W. (2002) BioTechniques 29: 128-145; Hoogenboom H., and Chames P. (2000) Immunology Today 21 :371-378), antibodies isolated from an animal ( e.g., a mouse) that is transgenic for human immunoglobulin genes (see e.g., Taylor, L. D., et al. (1992) Nuc I. Acids Res. 20:6287-6295; Kellermann S-A., and Green L. L. (2002) Current Opinion in Biotechnology 13:593-597; Little M. et al. (2000) Immunology Today 21 :364-370) or antibodies prepared, expressed, created or isolated by any other means that involves splicing of human immunoglobulin gene sequences to other DNA sequences. Such recombinant human antibodies have variable and constant regions derived from human germline immunoglobulin sequences. In certain embodiments, however, such recombinant human antibodies are subjected to in vitro mutagenesis (or, when an animal transgenic for human Ig sequences is used, in vivo somatic mutagenesis) and thus the amino acid sequences of the VH and VL regions of the recombinant antibodies are sequences that, while derived from and related to human germline VH and VL sequences, may not naturally exist within the human antibody germline repertoire in vivo. One embodiment of the disclosure provides fully human antibodies capable of binding human hemojuvelin which can be generated using techniques well known in the art, such as, but not limited to, using human Ig phage libraries such as those disclosed in Jermutus et al., PCT publication No. WO 2005 / 007699 A2.

[0065] Reticulocyte hemoglobin content (CHr): As used herein, the term “Reticulocyte hemoglobin content (CHr),” refers to the hemoglobin level in reticulocytes, which are immature erythrocytes in circulation. The reticulocytes' hemoglobin content reflects the amount of iron available for hemoglobin production in the bone marrow. The reticulocyte hemoglobin content provides an indirect measure of the functional iron available for new red blood cell production over the previous several days (e.g., 3-4 days). In some embodiments, reticulocyte hemoglobin equivalent (Ret-He) is used in place of CHr (Toki etal., “Usefulness of Reticulocyte Hemoglobin Equivalent for Diagnosis of Iron Deficiency.” Blood. 2016; 128(22):3621).

[0066] Selective: As used herein, the term “selective” or “selectively” refers to the ability of a molecule to produce an effect in relation to its target molecule compared to a referencemolecule. For example, a molecule that selectively inhibits its target molecule means that this molecule is capable of inhibiting its target molecule with a degree that is distinguishable from a reference molecule in an inhibition assay or other inhibitory context. For example, with respect to an inhibitor, the term, “selectively inhibits,” refers to the ability of the inhibitor to inhibit its target molecule with a degree that is distinguishable from a reference molecule that is not substantially inhibited in an inhibition assay, e.g., to an extent that permit selective inhibition of the target molecule, as described herein. For example, the half maximal inhibitory concentration (IC50) for the target molecule and / or the reference molecule can be tested in a kinase potency assay as described in Asshoff, M. etal., Momelotinib inhibits ACVR1 / ALK2, decreases hepcidin production, and ameliorates anemia of chronic disease in rodents. Blood. 2017 Mar 30; 129(13): 1823-1830 (e.g., Kinase potency assay by Cama Biosciences). In this assay, inhibitor solution (e.g., solution containing the selective inhibitor to be tested) / kinase substrate is mixed with target molecule solution (e.g., ALK2) or reference molecule solution (e.g., JAK1 or JAK2), and incubated under room temperature for 1 hour. Once the reaction is terminated, the signal produced by enzymatic activity on the substrate can be measured. The half maximal inhibitor concentration for the target molecule and the reference molecule can be calculated. In some embodiments, a molecule described herein selectively binds to a target molecule. In some embodiments, a molecule described herein selectively inhibits to a target molecule. In some embodiments, a molecule described herein selectively antagonizes to a target molecule. In some embodiments, a molecule described herein selectively neutralizes to a target molecule.

[0067] Specifically binds: As used herein, the term “specifically binds” refers to the ability of a molecule to bind to a binding partner with a degree of affinity or avidity that enables the molecule to be used to distinguish the binding partner from an appropriate control in a binding assay or other binding context. With respect to an antibody, the term, “specifically binds”, refers to the ability of the antibody to bind to a specific antigen with a degree of affinity or avidity, compared with an appropriate reference antigen or antigens, that enables the antibody to be used to distinguish the specific antigen from others, e.g., to an extent that permits preferential targeting to certain cells, e.g., muscle cells, through binding to the antigen, as described herein. In some embodiments, an antibody specifically binds to a target if the antibody has a KD for binding the target of at least about 10'4M, 10'5M, 10'6M, 10'7M, 10'8M, 10'9M, 10'10M, 10'11M, 10'12M, 10'13M, or less. In some embodiments, an antibody specifically binds to hemojuvelin.

[0068] Subject: As used herein, the term “subject” refers to a mammal. In some embodiments, a subject is non-human primate, or rodent. In some embodiments, a subject is a human. In some embodiments, a subject is a patient, e.g., a human patient that has or is suspected of having a disease. In some embodiments, the subject is a human patient who has or is suspected of having a condition associated with barrier dysfunction. In some embodiments, the subject is a human patient who has or is suspected of having IBD and / or one or more related conditions, including Ulcerative Colitis (UC), Crohn’s Disease (CD), or IBD-unclassified (IBD-U).

[0069] Transferrin Saturation (TSAT%): As used herein, the term “transferrin saturation (TSAT%),” refers to a percentage value of serum iron divided by the total iron-binding capacity of the available transferrin, the main protein that binds iron in the blood. This value indicates how much serum iron is bound to transferrin. For instance, a value of 15% means that 15% of iron-binding sites of transferrin are being occupied by iron. A low transferrin saturation is a common indicator of iron deficiency whereas a high transferrin saturation may indicate iron overload or hemochromatosis. Transferrin saturation is also called transferrin saturation index (TSI) or transferrin saturation percentage (TS%).

[0070] Treatment: As used herein, the term “treating” or “treatment” refers to the application or administration of a composition including one or more active agents to a subject, who has a target disease or disorder, a symptom of the disease / disorder, or a predisposition toward the disease / disorder, with the purpose to cure, heal, alleviate, relieve, alter, remedy, ameliorate, improve, or affect the disorder, the symptom of the disease, or the predisposition toward the disease or disorder. Alleviating a target disease / disorder includes delaying or preventing the development or progression of the disease, or reducing disease severity.II. Methods for Treating Inflammatory Bowel Disease

[0071] Certain aspects of the disclosure relate to a recognition that inhibiting hemojuvelin in a subject that has barrier dysfunction (e.g., intestinal mucosal barrier dysfunction) reduces inflammation in the subjects. Generally, the term “Barrier Dysfunction” refers to the aberrant function of an epithelial barrier that lines an organ system or other bodily structure, e.g., gastrointestinal system, skin, and airways, and in particular, a disruption in barrier integrity, e.g., a disruption sufficient to increase permeability across the barrier or otherwise permit transport of molecules across the barrier beyond physiologically normal levels. Under normal conditions, the epithelial tissue acts as a barrier by forming a continuous layer protects thebody from various factors, e.g., environmental stress, physical and chemical damage, infections, and allergens (see, e.g., Sozener et cd., Environmental factors in epithelial barrier dysfunction, Clinical Reviews in Allergy and Immunology, Volume 145, Issue 6, Pl 517-1528, June 2020). In some embodiments, barrier dysfunction is intestinal barrier dysfunction. In some embodiments, barrier dysfunction is skin barrier dysfunction. In some embodiments, barrier dysfunction is airway barrier dysfunction.

[0072] In some embodiments, methods and related compositions provide herein are useful for inhibiting inflammation (e.g., intestinal mucosal inflammation) in a subject having IBD (e.g., UC, CD, IBD-U). In some embodiments, composition and methods provide herein can be used for the purpose of reducing intestinal mucosal inflammation, reducing intestinal bleeding, improving clinical symptoms, inducing remission, and / or maintaining remission in a subject having IBD (e g., UC, CD, IBD-U).

[0073] In some embodiments, the present disclosure provides compositions (e.g., anti-HJV antibodies) and methods for treating a subject having intestinal barrier dysfunction.

[0074] Generally, the term “Intestinal Barrier Dysfunction” refers to a barrier dysfunction of an epithelial barrier that lines the gastrointestinal track. The intestinal barrier has selective permeability due to protein-protein networks and is designed to absorb and exchange nutrients, water, and electrolytes, while providing an effective defense against microbes and toxins. The intestinal barrier comprises various layers, including a mucous layer (i.e., mucosal barrier) and an epithelium layer. The epithelium layer includes an epithelium having a single layer of columnar epithelial cells, including absorbent enterocytes, secretory goblet cells, Paneth cells, and enteroendocrine cells. The mucous layer in the gut is thick and adherent to the intestinal epithelium. It is essential for the selective permeability of the intestinal barrier. The mucus layer is composed of two layers: an inner layer that is firmly attached to the epithelial cells and an outer layer that is thicker but much looser and less adherent. The inner mucosal layer does not allow bacteria to penetrate, keeping the surface of epithelial cells free of direct contact with bacteria. In contrast, the outer mucosal layer harbors commensal bacteria that prevent the entry of pathogenic bacteria into the outer as well as inner mucus layer. The mucous layer prevents direct contact of large particles and microorganisms with epithelial cells, and allows small molecules to pass and protects epithelial cells from digestive enzymes. In addition to its protective function, the intestinal epithelium controls the absorption and exchange of the nutrients, water, and electrolytes. In addition, the intestinal barrier includes various factors, such as intestinal alkaline phosphatase and antibacterial peptides, that further function to maintains pH, absorption nutrient, andprovide anti-microbial defenses. In some embodiments, a subject with IBD has increased intestinal permeability relative to a subject that does not have intestinal barrier dysfunction. In some embodiments, a subject with IBD has mucosal barrier dysfunction.

[0075] In some embodiments, intestinal barrier function is critical for normal homeostasis of the gut. In some embodiments, intestinal barrier dysfunction is intestinal mucosal barrier dysfunction. In some embodiments, intestinal epithelial cell injury leads to intestinal barrier dysfunction. In some embodiments, intestinal epithelial cell injury and / or cell death leads to intestinal barrier dysfunction. In some embodiments, loss of tight junction between intestinal epithelial cells leads to intestinal barrier dysfunction. In some embodiments, loss of intestinal mucous leads to intestinal barrier dysfunction. In some embodiments, intestinal barrier dysfunction leads to increased intestinal permeability. In some embodiments, the breakdown or dysfunction of intestinal barrier is associated with local as well as systemic consequences largely related to direct contact of bacteria / bacterial products with the epithelial cells, and translocation of these to the systemic circulation. Direct contact with bacteria / bacterial products leads to the activation of immune cells resulting in the secretion of proinflammatory mediators that perpetuate local inflammation. In some embodiments, local intestinal inflammation underlies the development of a number of gastrointestinal diseases, such as inflammatory bowel disease including Crohn’s disease, and ulcerative colitis (see, e.g., Ghosh et al., Intestinal Barrier Dysfunction, LPS Translocation, and Disease Development, J Endocr Soc. 2020 Feb 1; 4(2): bvz039). In some embodiments, a subject with IBD has mucosal barrier dysfunction.

[0076] In some aspects, the present disclosure provides compositions (e.g., anti-HJV antibodies) and methods for treating a subject having inflammatory bowel disease (e.g., ulcerative colitis (UC), Crohn’s disease (CD), or IBD-unclassified (IBD-U)), the method comprising administering the subject a hemojuvelin antagonist (e.g., an anti-HJV antibody described herein). In some embodiments, methods and related compositions provide herein a useful for inhibiting inflammation (e.g., intestinal mucosal inflammation) in a subject having IBD. In some embodiments, composition and methods provide herein can be used for purpose of reducing intestinal mucosal inflammation, reducing intestinal bleeding, improving clinical symptoms, inducing and maintain remission in a subject having IBD (e.g., UC, CD, or IBD-U).

[0077] Generally, the term “Inflammatory Bowel Disease” (“IBD”) refers to a group of diseases characterized by repetitive episodes of inflammation of the gastrointestinal tract caused by an abnormal immune response. In some embodiments, inflammatory bowel diseaseencompasses two types of idiopathic intestinal disease that are differentiated by their location and depth of involvement in the bowel wall, e.g., UC or CD. In some embodiments, inflammatory bowel disease encompasses IBD-U, which is an inflammatory intestinal condition that shows one or more symptoms of both Crohn's disease (CD) and ulcerative colitis (UC). In some embodiments, a subject having IBD (e.g., UC, CD, IBD-U) has a genetic predisposition for IBD. In some embodiments, a subject may have genetic variant associated with IBD in one or more of N0D2, ATG16L1, IRGM, IL23R, CARD9, CLEC7A, RNF186, HL A, TNF, TNFSF15 / TL1A, LR4, IL-6, IL-1, IL- 10, IL- 12, IL-23, IL 17, TLR2, TLR9, Fas-L, CASP9, and ATG16L1 or PRDM1 genes. In some embodiments, a subject having IBD may be at risk of developing or have developed colorectal cancer.

[0078] In some embodiments, an IBD is ulcerative colitis (UC). UC involves diffuse inflammation of the colonic mucosa. In some embodiments, UC affects the rectum and the subject has proctitis. In some embodiments, UC affected area may extend into the sigmoid and the subject has proctosigmoiditis. In some embodiments, UC may affect the gastrointestinal tract beyond the sigmoid and the subject has distal ulcerative colitis. In some embodiments, UC may affect the entire colon up to the cecum, and the subject has pancolitis. In some embodiments, a subject that has UC has one or more of the symptoms including abdominal pain, blood and / or pus in the stools, diarrhea, fever, weight loss, or tenesmus. In some embodiments, a subject that has UC has atypical expression of perinuclear antineutrophil cytoplasmic antibody (P-ANCA) relative to healthy subjects. In some embodiments, a subject that has UC has similar expression of anti-Saccharomyces cerevisiae antibodies (ASCA) relative to healthy subjects.

[0079] In some embodiments, an IBD is Crohn’s disease (CD). CD results in transmural ulceration of any portion of the gastrointestinal (GI) tract. In some embodiments, CD affects the terminal ileum and colon. In some embodiments, CD affects any part of the GI tract, including the oral cavity and esophagus. In some embodiments, a subject that has CD is at risk of developing or has fistula (i.e., the subject has fistulizing Crohn’s disease) (see, Scharl et al.. Fistulizing Crohn’s Disease, Clin Transl Gastroenterol. 2017 Jul; 8(7): el06). In some embodiments, a subject that has CD is at risk of developing or has intestinal strictures (see, e.g., Lin etal., Therap Adv Gastroenterol. 2022; 15: 17562848221104951). In some embodiments, a subject that has CD has one or more of symptoms including diarrhea, fever, fatigue, abdominal pain, abdominal cramping, bloody stool, mouth sores, reduced appetite, weight loss, and / or fistula. In some embodiments, a subject that has CD has similarexpression of P-ANCA relative to healthy subjects. In some embodiments, a subject that has UC has atypical expression of ASCA relative to healthy subjects.

[0080] In some embodiments, an IBD is unclassified (IBD-U). IBD-U, also known as indeterminate colitis, refers to colitis that cannot be identified properly as CD or UC (see Zhou, N., et al. (2011). Inflammatory bowel disease unclassified. Journal of Zhejiang University Science B, 12, 280-286.; Shao, Y. et al. (2024) Clinical features of inflammatory bowel disease unclassified: a case-control study. BMC Gastroenterol 24, 105). In some embodiments, IBD-U comprises one or more symptoms or histopathological features of UC and / or one or more symptoms or histopathological features of CD. In some embodiments, IBD-U comprises transmural inflammation or crypt abscesses. In some embodiments, IBD-U lacks transmural lymphoid aggregates or fissuring ulcers. In some embodiments, IBD-U comprises presence of mild, usually focal basal lympho-plasmacytosis in samples from the subject. In some embodiments, IBD-U comprises minimal architectural abnormalities in samples from the subject. In some embodiments, a subject that has IBD-U has a history of inflammatory diarrhea. In some embodiments, a subject that has IBD-U has liver disease. In some embodiments, a subject that has IBD-U and intestinal hemorrhaging develops UC. In some embodiments, a subject that has IBD-U and hypoalbuminemia develops UC. It is understood that the compositions and methods described herein (e.g., administration of an anti-HJV antibody) are application for treating IBD-U.

[0081] In some embodiments, besides the GI tract, a subject that has IBD (e.g., UC, CD, IBD-U) has extraintestinal manifestations (EIM) (see, e.g., Levine et al.. Extraintestinal Manifestations of Inflammatory Bowel Disease, Gastroenterol Hepatol (N Y). 2011 Apr; 7(4): 235-241; Malik et al.. Extraintestinal Manifestations of Inflammatory Bowel Disease, In: StatPearls [Internet], Treasure Island (FL): StatPearls Publishing; 2023 Jan. 2023 Mar 6). In some embodiments, a subject that has IBD (e.g., UC, CD, IBD-U) has one or more EIM including but are not limited to musculoskeletal manifestations such as axial spondyloarthritis (SpA) (e.g., Ankylosing spondylitis (AS) and sacroiliitis) and / or peripheral spondyloarthritis (SpA) (e.g., pauciarticular (Type 1) peripheral arthritis and polyarticular (Type 2) peripheral arthritis); cutaneous manifestations such as erythema nodosum (EN), pyoderma gangrenosum, Sweet syndrome, and / or oral aphthous lesions; ocular manifestations such as episcleritis, scleritis, and / or uveitis; hepatobiliary manifestations such as primary sclerosing cholangitis (PSC), autoimmune / granulomatous hepatitis, fatty liver disease, cholestasis, gallstone formation, and autoimmune pancreatitis; other manifestations including anemia, urological manifestations (e.g., nephrolithiasis with possible urinary outflow obstruction, orinterstitial nephritis), thromboembolic disorders (deep vein thrombosis, or pulmonary embolism), heart disease, stroke, fatigue, interstitial pneumonia, or metabolic bone disorder.

[0082] IBD is a condition that is characterized by intermittent periods of active disease (flare-ups) and little or no disease activity (remission). In some embodiments, a subject that has IBD (e.g., UC, CD, IBD-U) can be in an active state of IBD. In some embodiments, active state of IBD or active IBD refers to an episode when the subject is having a flare-ups or flaring of symptoms. In some embodiments, a subject that has IBD is in remission phase where the subject may go a period of time (e.g., weeks to months) with little to no symptoms. In some embodiments, the subject that has IBD (e.g., UC, CD, IBD-U) may be in active phase of IBD where the symptoms returning after being in remission for a period of time (i.e., relapse). In some embodiments, a subject that is in active phase of IBD may also has one or more extraintestinal manifestations of IBD. In some embodiments, a subject having active IBD (e.g., active US, active CD, active IBD-U) is in acute phase of IBD. In some embodiments, a subject with active IBD (e.g., active UC, active CD, active IBD-U) has have one or more symptoms associated with IBD (e.g., UC, CD, IBD-U). In some embodiments, a subject with active IBD (e.g., active UC, active CD, active IBD-U) has increased inflammation (e.g., systemic and / or local inflammation) relative to the subject during remission. In some embodiments, a subject with active IBD (e.g., active UC, active CD, active IBD-U) has one or more endoscopic findings associated with IBD. In some embodiments, a subject goes into remission after the active phase of IBD.

[0083] In some embodiments, a subject having IBD is in clinical remission. In some embodiments, a subject having IBD is in endoscopic remission. In some embodiments, a subject having IBD is in biochemical remission. In some embodiments, a subject having IBD is in histologic remission. In some embodiments, a subject having IBD is in surgical remission.

[0084] In some embodiments, a subject is in chronic phase of IBD (e.g., including remission phase and the period after the acute flare up during active IBD).

[0085] In some embodiments, the subject has inflammation associated with barrier dysfunction. In some embodiments, the subject has increased intestinal permeability relative to a subject that does not have intestinal barrier dysfunction. In some embodiments, the subject has aberrant immune response to gastrointestinal track microbiome. In some embodiments, the inflammation in the intestine further damages the epithelial cells in the intestine. In some embodiments, injury to epithelial cells further exacerbates the inflammation.

[0086] In some embodiments, the subject has reduced liver function. Reduced liver function occurs commonly in subjects having IBD; for example, subjects having IBD may also have chronic liver disease, abnormal liver function, cirrhosis, liver inflammation, primary sclerosing cholangitis, autoimmune hepatitis, primary biliary cholangitis, or drug- induced liver injury (e.g., as a result of IBD treatment). Liver function may be assessed by any suitable assays. In some embodiments, liver function in the subject is assessed by determining a level of one or more liver enzymes (e.g., AST, ALT). In some embodiments, the subject has a baseline level of aspartate aminotransferase (AST) of less than 3. Ox upper limit of normal (ULN). In some embodiments, the subject has a baseline level of alanine transaminase (ALT) of <3. Ox ULN.

[0087] In some embodiments, the subject has systemic inflammation. Systemic inflammation can be measured using any suitable method, e.g., total white blood cell (WBC) count, neutrophil count, lymphocyte count, and / or levels of proinflammatory biomarkers (e.g., TNF-a, interferon y, IL-1, IL-6, IL-8, IL-17, IL-12, IL-23, IL-25, C-reactive protein (CRP) etc.). In some embodiments, the subject has local intestinal inflammation. Local intestinal inflammation can be measured by any suitable methods, e.g., endoscopy, immune cell infiltration in biopsy tissue, fecal biomarkers, etc.

[0088] In some embodiments, the subject has inflammatory bowel disease (IBD). In some embodiments, the subjects have one or more gene variants that predisposes the subject to having IBD. In some embodiments, the subject has one or more gene variants in NOD2, ATG16L1, IRGM, IL23R, CARD9, CLEC7A, RNF186, HL A, TNF, TNFSF15 / TL1A, LR4, IL-6, IL- 1, IL- 10, IL- 12, IL-23, IL 17, TLR2, TLR9, Fas-L, CASP9, and ATG16L1 or PRDM1 genes (see, e.g., Hadad etal., The Genetics of Inflammatory Bowel Disease, Mol Diagn Ther (2023); Venema et al., The genetic background of inflammatory bowel disease: from correlation to causality, J Pathol. 2017 Jan;241(2): 146-158; Jarmakiewicz-Czaja et al., Genetic and Epigenetic Etiology of Inflammatory Bowel Disease: An Update, Genes 2022, 13(12), 2388). IBD (e.g., UC, CD, IBD-U) can be classified by severity (mild, moderate, or severe) and / or location.

[0089] In some embodiments, the subject has IBD associated with intestinal barrier dysfunction. In some embodiments, the subject has increased intestinal mucosal barrier dysfunction associated with IBD. In some embodiments, the subject that has IBD has a defective mucous layer in the intestine. In some embodiments, the subject that has IBD has altered pattern-recognition receptors on intestinal epithelial cells and immune cells. In someembodiments, the subject that has IBD has increased intestinal permeability. In some embodiments, the subject that has IBD has increased contact between intestinal microbiome and the epithelial cells. In some embodiments, the subject that has IBD has aberrant immune response to the intestine microbiome and / or intestinal contents. In some embodiments, a subject that has IBD (e.g., UC, CD, IBD-U) has immune cell (e.g., neutrophils, macrophages, dendritic cells, and / or natural killer T cells) infiltration to the mucous layer of the intestinal wall relative to, e.g., a subject that does not have IBD.

[0090] IBD is a condition that is characterized by intermittent periods of active disease (flare-ups) and little or no disease activity (remission). In some embodiments, a subject that has IBD (e.g., UC, CD, IBD-U) can be in an active state of IBD. UC and CD are classified by severity (mild, moderate, or severe). In some embodiments, active state of IBD” and “active IBD” refer to an episode during which the subject is having a flare-up or flaring of symptoms. In some embodiments, a subject that has IBD is in remission phase of IBD. A “remission phase” refers to a period of time (e.g., weeks to months) during which the subject experiences little to no symptoms.

[0091] In some embodiments, the subject that has IBD (e.g., UC, CD, IBD-U) may be in active phase of IBD where the symptoms returning after being in remission for a period of time (i.e., relapse). In some embodiments, a subject that is in active phase of IBD may also has one or more extraintestinal manifestations of IBD. In some embodiments, a subject having active IBD (e.g., active UC, CD, or IBD-U) is in acute phase of IBD. In some embodiments, a subject with active IBD (e.g., active UC, CD, or IBD-U) has have one or more symptoms associated with IBD (e.g., active UC, CD, or IBD-U). In some embodiments, a subject with active IBD (e.g., active UC, CD, or IBD-U) has increased inflammation (e.g., systemic and / or local inflammation) relative to the subject during remission. In some embodiments, a subject with active IBD (e.g., active UC, CD, or IBD-U) has one or more endoscopic findings associated with IBD.

[0092] In some embodiments, a subject goes into remission after the active phase of IBD. In some embodiments, a subject having IBD is in clinical remission. In some embodiments, a subject in clinical remission of IBD when the symptoms of IBD have lessened to the point the symptoms are mostly absent or gone. In some embodiments, a subject in clinical remission has a disease index score within the range of remission. In some embodiments, a subject having IBD is in endoscopic remission. In some embodiments, a subject in endoscopic remission when no inflammation is seen during an endoscopic (e.g., colonoscopy or a sigmoidoscopy) examination. In some embodiments, a subject in endoscopic remission hasan endoscopic score for IBD (e.g., UC, CD, IBD-U) within the range of remission. In some embodiments, a subject having IBD is in biochemical remission. In some embodiments, a subject having IBD is in biochemical remission when laboratory tests done on the blood or the stool don't show any of the hallmark signs of IBD (e.g., no elevated values of the inflammatory markers including c-reactive protein (CRP) and / or fecal calprotectin). In some embodiments, a subject having IBD is in histologic remission. In some embodiments, a subject having IBD is in histologic remission when no inflammation is observed from a biopsy tissue. In some embodiments, a subject having IBD is in surgical remission. In some embodiments, a subject having IBD is in surgical remission when there is no active disease following surgical resection of the affected intestinal segments (e.g., removing the affected intestinal segment reduced inflammation and / or symptoms). In some embodiments, a subject is in chronic phase of IBD (e.g., including remission phase and the period after the acute flare up during active IBD).

[0093] In some embodiments, the disclosure provides methods comprising administering to the subject a pre-determined amount of an anti-HJV antibody. In some embodiments, the predetermined amount is an effective amount. In some embodiments, the effective amount is an amount effective to induce one or more desired effects. In some embodiments, an effective amount is an amount of anti-HJV antibody that confers reduced intestinal inflammation, reduced intestinal bleeding, reduced weight loss, reduce fatigue, improve endoscopic appearance, inducing remission, and / or prolonging remission. In some embodiments, the methods provided herein inhibits inflammation in a subject that has inflammation associated with barrier dysfunction. In some embodiments, the effective amount is a therapeutic effect, e.g., an amount sufficient to confer a therapeutic effect on the subject (e.g., to treat intestinal barrier dysfunction, IBD). In some embodiments, the disclosure provides methods for treating barrier dysfunction in a subject, the methods comprising administering to the subject an effective amount of an anti-HJV antibody described herein.

[0094] In some embodiments, the present disclosure provides methods for inducing remission in a subject having active IBD (e.g., active UC or active CD), the method comprising administering to the subject an effective amount of an anti-HJV antibody. In some embodiments, the administration induces remission in a subject having active IBD (e.g., active UC or active CD). In some embodiments, the administration induces clinical remission in a subject having active IBD (e.g., active UC or active CD). In some embodiments, the administration induces endoscopic remission in a subject having active IBD (e.g., active UC or active CD). In some embodiments, the administration induces histologic remission in asubject having active IBD (e.g., active UC or active CD). In some embodiments, the administration induces biochemical remission in a subject having active IBD (e.g., active UC or active CD). In some embodiments, the administration maintains remission after surgery in a subject having active IBD (e.g., UC, CD, IBD-U).

[0095] In some embodiments, the present disclosure provides methods for maintaining remission (e.g., prolonging remission period between two flare ups) in a subject having IBD (e.g., active UC or active CD), the method comprising administering to the subject an effective amount of an anti-HJV antibody. In some embodiments, the administration increases the remission period in a subject having IBD (e.g., UC, CD, IBD-U) by at least 1 day, at least 5 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least four weeks, at least four weeks, at least five weeks, at least six weeks, at least seven weeks, at least eight weeks, at least nine weeks, at least ten weeks, at least 1 month, at least two months, at least three months, at least four months, at least five months, at least six months, at least seven months, at least eight months, at least nine months, at least ten months, at least eleven months, at least twelve months, at least thirteen months, at least 15 months, at least 18 months, at least 24 months, at least 28 months, at least 30 months, at least 32 months, at least 36 months, at least 38 months, at least 40 months, at least 45 months, at least 48 months, at least one year, at least two years, at least three years, at least four years, at least 5 years, or more relative to relative to the subject prior to administration or a subject with IBD that did not receive the administration.

[0096] In some embodiments, the administration increases the remission period in a subject having IBD (e.g., UC, CD, IBD-U) in the range of 1-500 days, 1-450 days, 1-400 days, 1-300 days, 1-200 days, 1-100 days, 1-90 days, 1-80 days, 1-70 days, 1-60 days, 1-50 days, 1-40 days, 1-30 days, 1-20 days, 1-10 days, 1-5 days, 1-100 weeks, 1-90 weeks, 1-80 weeks, 1-70 weeks, 1-60 weeks, 1-50 weeks, 1-40 weeks, 1-30 weeks, 1-20 weeks, 1-10 weeks, 1-5 weeks, 1-4 weeks, 1-3 weeks, 1-2 weeks, 2-3 weeks, 2-4 weeks, 2-5 weeks, 2-6 weeks, 2-8 weeks, 2-10 weeks, 5-100 weeks, 5-90 weeks, 5-80 weeks, 5-70 weeks, 5-60 weeks, 5-50 weeks, 5-40 weeks, 5-30 weeks, 5-20 weeks, 5-10 weeks, 8-100 weeks, 8-90 weeks, 8-80 weeks, 8-70 weeks, 8-60 weeks, 8-50 weeks, 8-40 weeks, 8-30 weeks, 8-20 weeks, 8-10 weeks, 10-100 weeks, 10-90 weeks, 10-80 weeks, 10-70 weeks, 10-60 weeks, 10-50 weeks, 10-40 weeks, 10-30 weeks, 10-20 weeks, 15-100 weeks, 15-90 weeks, 15-80 weeks, 15-70 weeks, 15-60 weeks, 15-50 weeks, 15-40 weeks, 15-30 weeks, 15-20 weeks, 20-100 weeks, 20-90 weeks, 20-80 weeks, 10-70 weeks, 20-60 weeks, 20-50 weeks, 20-40 weeks, 20-30 weeks, 30-100 weeks, 30-90 weeks, 30-80 weeks, 30-70 weeks, 30-60 weeks, 30-50 weeks,30-40 weeks, 40-100 weeks, 40-90 weeks, 40-80 weeks, 40-70 weeks, 40-60 weeks, 40-50 weeks, 50-100 weeks, 50-90 weeks, 50-80 weeks, 50-70 weeks, 50-60 weeks, 60-100 weeks, 60-90 weeks, 60-80 weeks, 60-70 weeks, 70-100 weeks, 70-90 weeks, 70-80 weeks, 80-100 weeks, 80-90 weeks, 90-100 weeks, 1-100 months, 1-90 months, 1-80 months, 1-70 months, 1-60 months, 1-50 months, 1-40 months, 1-30 months, 1-20 months, 1-10 months, 1-5 months, 1-4 months, 1-3 months, 1-2 months, 2-3 months, 2-4 months, 2-5 months, 2-6 months, 2-8 months, 2-10 months, 5-100 months, 5-90 months, 5-80 months, 5-70 months, 5- 60 months, 5-50 months, 5-40 months, 5-30 months, 5-20 months, 5-10 months, 8-100 months, 8-90 months, 8-80 months, 8-70 months, 8-60 months, 8-50 months, 8-40 months, 8- 30 months, 8-20 months, 8-10 months, 10-100 months, 10-90 months, 10-80 months, 10-70 months, 10-60 months, 10-50 months, 10-40 months, 10-30 months, 10-20 months, 15-100 months, 15-90 months, 15-80 months, 15-70 months, 15-60 months, 15-50 months, 15-40 months, 15-30 months, 15-20 months, 20-100 months, 20-90 months, 20-80 months, 10-70 months, 20-60 months, 20-50 months, 20-40 months, 20-30 months, 30-100 months, 30-90 months, 30-80 months, 30-70 months, 30-60 months, 30-50 months, 30-40 months, 40-100 months, 40-90 months, 40-80 months, 40-70 months, 40-60 months, 40-50 months, 50-100 months, 50-90 months, 50-80 months, 50-70 months, 50-60 months, 60-100 months, 60-90 months, 60-80 months, 60-70 months, 70-100 months, 70-90 months, 70-80 months, 80-100 months, 80-90 months, 90-100 months, 1-10 years, 1-9 years, 1-8 years, 1-7 years, 1-6 years, 1-5 years, 1-4 years, 1-3 years, 1-2 years, 2-10 years, 2-9 years, 2-8 years, 2-7 years, 2-6 years, 2-5 years, 2-4 years, 2-3 years, 3-10 years, 3-9 years, 3-8 years, 3-7 years, 3-6 years, 3- 5 years, 3-4 years, 4-10 years, 4-9 years, 4-8 years, 4-7 years, 4-6 years, 4-5 years, 5-10 years, 5-9 years, 5-8 years, 5-7 years, 5-6 years, 6-10 years, 6-9 years, 6-8 years, 6-7 years, 7- 10 years, 7-9 years, 7-8 years, 8-10 years, 8-9 years, or 9-10 years relative to relative to the subject prior to administration or a subject with IBD that did not receive the administration.

[0097] In some embodiments, a subject having IBD (e.g., UC, CD, IBD-U) is receiving or has previously received one or more treatments for IBD. In some embodiments, a subject having IBD (e.g., UC, CD, IBD-U) is receiving one or more treatment including but not limited to aminosalicylates (5-ASA), corticosteroids, sphingosine 1-phosphate receptor modulators (e.g., Estrasimod, Ozanimod), immunomodulators (e.g., Azathioprine, 6- mercaptopurine, Cyclosporine, or Tacrolimus), Janus kinase (JAK) inhibitors (e.g., Upadacitinib, Tofacitinib), tumor necrosis factor (TNF) inhibitors (e.g., adalimumab, Certolizumab pegol, Infliximab, Golimumab), integrin antagonists (e.g., natalizumab, Vedolizumab), interleukin (IL)-23 antagonists (e.g., Risankizumab-rzaa), or IL-12 / IL23antagonists (e.g., Ustekinumab), nicotine, Sulfasalazine (e.g., Azulfidine, Salazopyrin, Sulazine), Mesalamine, Olsalazine, Balsalazide, or Azathioprine. In some embodiments, a subject having CD is resistant to existing therapy for IBD (e.g., therapeutic agents for IBD described herein).

[0098] In some embodiments, the disclosure herein provides methods for treating a subject having IBD (e.g., UC, CD, IBD-U) that is resistant to other existing therapies such as 5-ASA, corticosteroids, immunomodulators, and / or TNF inhibitors, the method comprising administering to the subject an effective amount of an anti-HJV antibody. In some embodiments, the administration is effective in reducing one or more symptoms for a subject having IBD (e.g., UC, CD, IBD-U) that is resistant to other existing therapies (e.g., 5-ASA, corticosteroids, immunomodulators, and / or TNF inhibitors). In some embodiments, the administration is effective in reducing CD Al score in a subject having IBD (e.g., UC, CD, IBD-U) that is resistant to other existing therapies (e.g., 5-ASA, corticosteroids, immunomodulators, and / or TNF inhibitors). In some embodiments, the administration is effective in reducing disease severity (e.g., disease severity based on the disease indexes as described herein) in a subject having IBD (e.g., UC, CD, IBD-U) that is resistant to other existing therapies (e.g., 5-ASA, corticosteroids, immunomodulators, and / or TNF inhibitors).

[0099] In some embodiments, the administration is effective in improving endoscopic appearances in a subject having IBD (e.g., UC, CD, IBD-U) that is resistant to other existing therapies (e.g., 5-ASA, corticosteroids, immunomodulators, and / or TNF inhibitors). In some embodiments, the administration is effective in improving endoscopic appearances in a subject having IBD (e.g., UC, CD, IBD-U) that is resistant to other existing therapies (e.g., 5- ASA, corticosteroids, immunomodulators, and / or TNF inhibitors). In some embodiments, the administration is effective in inducing remission in a subject having IBD (e.g., UC, CD, IBD- U) that is resistant to other existing therapies (e.g., 5-ASA, corticosteroids, immunomodulators, and / or TNF inhibitors). In some embodiments, the administration is effective in prolonging remission in a subject having IBD (e.g., UC, CD, IBD-U) that is resistant to other existing therapies (e.g., 5-ASA, corticosteroids, immunomodulators, and / or TNF inhibitors). In some embodiments, an-anti-HJV described herein can be combined with any existing IBD therapeutic agents (e.g., any of the therapeutic agents described herein) for treating IBD. In some embodiments, besides the GI tract, a subject that has IBD (UC, CD, IBD-U) has extraintestinal manifestations (EIM) (see, e.g., Levine et al.. Extraintestinal Manifestations of Inflammatory Bowel Disease, Gastroenterol Hepatol (N Y). 2011 Apr;7(4): 235-241; Malik et aL, Extraintestinal Manifestations of Inflammatory Bowel Disease, In: StatPearls [Internet], Treasure Island (FL): StatPearls Publishing; 2023 Jan. 2023 Mar 6). [000100] In some embodiments, a subject that has IBD (UC, CD, IBD-U) has one or more EIM including but are not limited to musculoskeletal manifestations such as axial spondyloarthritis (SpA) (e.g., Ankylosing spondylitis (AS) and sacroiliitis) and / or peripheral spondyloarthritis (SpA) (e.g., pauciarticular (Type 1) peripheral arthritis and polyarticular (Type 2) peripheral arthritis); cutaneous manifestations such as erythema nodosum (EN), pyoderma gangrenosum, Sweet syndrome, and / or oral aphthous lesions; ocular manifestations such as episcleritis, scleritis, and / or uveitis; hepatobiliary manifestations such as primary sclerosing cholangitis (PSC), autoimmune / granulomatous hepatitis, fatty liver disease, cholestasis, gallstone formation, and autoimmune pancreatitis; other manifestations including anemia, urological manifestations (e.g., nephrolithiasis with possible urinary outflow obstruction, or interstitial nephritis), thromboembolic disorders (deep vein thrombosis, or pulmonary embolism), heart disease, stroke, fatigue, interstitial pneumonia, or metabolic bone disorder.[000101] In some embodiments, the present disclosure provides methods for reducing one or more extraintestinal manifestation in a subject having IBD, the method comprising administering to the subject an effective amount of an anti-HJV antibody. In some embodiments, the administration reduces the occurrence of one or more of the extraintestinal manifestation by the range of 1%- 100%, 5%-100%, 5%-90%, 5%-80%, 5%-70%, 5%-60%, 5%-50%, 5%-40%, 5%-30%, 5%-20%, 5%-10%, 10%-100%, 10%-90%, 10%-80%, 10%- 70%, 10%-60%, 10%-50%, 10%-40%, 10%-30%, 10%-20%, 20%-100%, 20%-90%, 20%- 80%, 20%-70%, 20%-60%, 20%-50%, 20%-40%, 20%-30%, 30%-100%, 30%-90%, 30%- 80%, 30%-70%, 30%-60%, 30%-50%, 30%-40%, 40%-100%, 40%-90%, 40%-80%, 40%- 70%, 40%-60%, 40%-50%, 50%-100%, 50%-90%, 50%-80%, 50%-70%, 50%-60%, 60%- 100%, 60%-90%, 60%-80%, 60%-70%, 70%-100%, 70%-90%, 70%-80%, 80%-100%, 80%- 90%, or 90%-100% relative to the subject prior to administration or to a subject that did not receive the administration.[000102] In some embodiments, a subject that has IBD (e.g., UC, CD, IBD-U) has increased circulating immune cell (e.g., neutrophils, macrophages, dendritic cells, and / or natural killer T cells) relative to, e.g., a subject that does not have IBD. In some embodiments, a subject that has IBD (e.g., UC, CD, IBD-U) has increased levels of circulating proinflammatorycytokines (e.g., TNF-a, interferon y, IL-1, IL-6, IL-8, IL-17, IL-12, IL-23, IL-25, C-reactive protein (CRP) etc.)[000103] In some embodiments, the present disclosure provides methods for reducing inflammation in a subject having IBD (e.g., UC, CD, IBD-U) by administering a subject an effective amount of an anti-HJV antibody described herein. In some embodiments, administration of an anti-HJV antibody described herein reduces systemic inflammation in a subject having IBD (e.g., UC, CD, IBD-U). Systemic inflammation can be measured by any suitable methods, e.g., total white blood cell count, neutrophil count, lymphocyte count, levels of proinflammatory cytokines (e.g., TNF-a, interferon y, IL-1, IL-6, IL-8, IL-17, IL- 12, IL-23, IL-25, C-reactive protein (CRP)), etc.[000104] In some embodiments, administration of an anti-HJV antibody described herein reduces systemic inflammation (e.g., total white blood cell count, neutrophil count, lymphocyte count, levels of proinflammatory cytokines (e.g., TNF-a, interferon y, IL-1, IL-6, IL-8, IL-17, IL-12, IL-23, IL-25, C-reactive protein (CRP)) in a subject having IBD (e.g., UC, CD, IBD-U) relative to the subject prior to administration or a subject with IBD that did not receive the administration by at least 1%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%. In some embodiments, administration of an anti-HJV antibody described herein reduces systemic inflammation (e.g., total white blood cell count, neutrophil count, lymphocyte count, levels of proinflammatory cytokines (e.g., TNF-a, interferon y, IL-1, IL-6, IL-8, IL-17, IL-12, IL-23, IL-25, C-reactive protein (CRP)) in a subject with IBD (e.g., UC, CD, IBD-U) relative to the subject prior to administration or to a subject with IBD that did not receive the administration, by between 1% and 100%, between 5% and 100%, between 5% and 90%, between 5% and 80%, between 5% and 70%, between 5% and 60%, between 5% and 50%, between 5% and 40%, between 5% and 30%, between 5% and 20%, between 5% and 15%, between 10% and 100%, between 10% and 90%, between 10% and 80%, between 10% and 70%, between 10% and 60%, between 10% and 50%, between 10% and 40%, between 10% and 30%, between 10% and 20%, between 10% and 15%, between 20% and 100%, between 20% and 90%, between 20% and 80%, between 20% and 70%, between 20% and 60%, between 20% and 50%, between 20% and 40%, between 20% and 30%, between 30% and 100%, between 30% and 90%, between 30% and 80%, between 30% and 70%, between 30% and 60%, between 30% and 50%, between 30% and 40%, between 40% and 100%, between 40% and 90%, between 40% and 80%, between 40% and 70%, between40% and 60%, between 40% and 50%, between 50% and 100%, between 50% and 90%, between 50% and 80%, between 50% and 70%, between 50% and 60%, between 60% and 100%, between 60% and 90%, between 60% and 80%, between 60% and 70%, between 70% and 100%, between 70% and 90%, between 70% and 80%, between 80% and 100%, between 80% and 90%, or between 90% and 100%.[000105] In some embodiments, administration of an anti-HJV antibody described herein reduces of total white blood cell count in a subject having IBD (e.g., UC, CD, IBD-U) relative to the subject prior to administration or a subject with IBD that did not receive the administration by at least 1%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%. In some embodiments, administration of an anti-HJV antibody described herein reduces of total white blood cell count in the subject relative to the subject prior to administration or to a subject with IBD that did not receive the administration, by between 1% and 100%, between 5% and 100%, between 5% and 90%, between 5% and 80%, between 5% and 70%, between 5% and 60%, between 5% and 50%, between 5% and 40%, between 5% and 30%, between 5% and 20%, between 5% and 15%, between 10% and 100%, between 10% and 90%, between 10% and 80%, between 10% and 70%, between 10% and 60%, between 10% and 50%, between 10% and 40%, between 10% and 30%, between 10% and 20%, between 10% and 15%, between 20% and 100%, between 20% and 90%, between 20% and 80%, between 20% and 70%, between 20% and 60%, between 20% and 50%, between 20% and 40%, between 20% and 30%, between 30% and 100%, between 30% and 90%, between 30% and 80%, between 30% and 70%, between 30% and 60%, between 30% and 50%, between 30% and 40%, between 40% and 100%, between 40% and 90%, between 40% and 80%, between 40% and 70%, between 40% and 60%, between 40% and 50%, between 50% and 100%, between 50% and 90%, between 50% and 80%, between 50% and 70%, between 50% and 60%, between 60% and 100%, between 60% and 90%, between 60% and 80%, between 60% and 70%, between 70% and 100%, between 70% and 90%, between 70% and 80%, between 80% and 100%, between 80% and 90%, or between 90% and 100%. Total circulating white blood cell count can be measured by any suitable methods, e.g., blood smear, flow cytometry, etc.[000106] In some embodiments, administration of an anti-HJV antibody described herein reduces total circulating neutrophil count in a subject having IBD (e.g., UC, CD, IBD-U) relative to the subject prior to administration or a subject with IBD that did not receive the administration by at least 1%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%. In someembodiments, administration of an anti-HJV antibody described herein reduces circulating neutrophil in the subject relative to the subject prior to administration or to a subject with IBD that did not receive the administration, by between 1% and 100%, between 5% and 100%, between 5% and 90%, between 5% and 80%, between 5% and 70%, between 5% and 60%, between 5% and 50%, between 5% and 40%, between 5% and 30%, between 5% and 20%, between 5% and 15%, between 10% and 100%, between 10% and 90%, between 10% and 80%, between 10% and 70%, between 10% and 60%, between 10% and 50%, between 10% and 40%, between 10% and 30%, between 10% and 20%, between 10% and 15%, between 20% and 100%, between 20% and 90%, between 20% and 80%, between 20% and 70%, between 20% and 60%, between 20% and 50%, between 20% and 40%, between 20% and 30%, between 30% and 100%, between 30% and 90%, between 30% and 80%, between 30% and 70%, between 30% and 60%, between 30% and 50%, between 30% and 40%, between 40% and 100%, between 40% and 90%, between 40% and 80%, between 40% and 70%, between 40% and 60%, between 40% and 50%, between 50% and 100%, between 50% and 90%, between 50% and 80%, between 50% and 70%, between 50% and 60%, between 60% and 100%, between 60% and 90%, between 60% and 80%, between 60% and 70%, between 70% and 100%, between 70% and 90%, between 70% and 80%, between 80% and 100%, between 80% and 90%, or between 90% and 100%. Total circulating neutrophil count can be measured by any suitable methods, e.g., blood smear, flow cytometry, etc.[000107] In some embodiments, administration of an anti-HJV antibody described herein reduces of circulating lymphocyte count in a subject having IBD (e.g., UC, CD, IBD-U) relative to the subject prior to administration or a subject with IBD that did not receive the administration by at least 1%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%. In some embodiments, administration of an anti-HJV antibody described herein reduces of circulating lymphocyte count in the subject relative to the subject prior to administration or to a subject with IBD that did not receive the administration, by between 1% and 100%, between 5% and 100%, between 5% and 90%, between 5% and 80%, between 5% and 70%, between 5% and 60%, between 5% and 50%, between 5% and 40%, between 5% and 30%, between 5% and 20%, between 5% and 15%, between 10% and 100%, between 10% and 90%, between 10% and 80%, between 10% and 70%, between 10% and 60%, between 10% and 50%, between 10% and 40%, between 10% and 30%, between 10% and 20%, between 10% and 15%, between 20% and 100%, between 20% and 90%, between 20% and 80%, between 20% and 70%, between 20% and 60%, between 20% and 50%, between 20% and 40%, between 20%and 30%, between 30% and 100%, between 30% and 90%, between 30% and 80%, between 30% and 70%, between 30% and 60%, between 30% and 50%, between 30% and 40%, between 40% and 100%, between 40% and 90%, between 40% and 80%, between 40% and 70%, between 40% and 60%, between 40% and 50%, between 50% and 100%, between 50% and 90%, between 50% and 80%, between 50% and 70%, between 50% and 60%, between 60% and 100%, between 60% and 90%, between 60% and 80%, between 60% and 70%, between 70% and 100%, between 70% and 90%, between 70% and 80%, between 80% and 100%, between 80% and 90%, or between 90% and 100%. Total circulating lymphocyte count can be measured by any suitable methods, e.g., blood smear, flow cytometry, etc. [000108] In some embodiments, administration of an anti-HJV antibody described herein reduces one or more circulating proinflammatory cytokines (e.g., TNF-a, interferon y, IL-1, IL-6, IL-8, IL-17, IL-12, IL-23, IL-25, C-reactive protein (CRP), etc.) in a subject having IBD (e.g., UC, CD, IBD-U) relative to the subject prior to administration or a subject with IBD that did not receive the administration by at least 1%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%. In some embodiments, administration of an anti-HJV antibody described herein reduces one or more circulating proinflammatory cytokines (e.g., TNF-a, interferon y, IL-1, IL-6, IL-8, IL-17, IL-12, IL-23, IL-25, C-reactive protein (CRP) etc.) in the subject relative to the subject prior to administration or to a subject with IBD that did not receive the administration, by between 1% and 100%, between 5% and 100%, between 5% and 90%, between 5% and 80%, between 5% and 70%, between 5% and 60%, between 5% and 50%, between 5% and 40%, between 5% and 30%, between 5% and 20%, between 5% and 15%, between 10% and 100%, between 10% and 90%, between 10% and 80%, between 10% and 70%, between 10% and 60%, between 10% and 50%, between 10% and 40%, between 10% and 30%, between 10% and 20%, between 10% and 15%, between 20% and 100%, between 20% and 90%, between 20% and 80%, between 20% and 70%, between 20% and 60%, between 20% and 50%, between 20% and 40%, between 20% and 30%, between 30% and 100%, between 30% and 90%, between 30% and 80%, between 30% and 70%, between 30% and 60%, between 30% and 50%, between 30% and 40%, between 40% and 100%, between 40% and 90%, between 40% and 80%, between 40% and 70%, between 40% and 60%, between 40% and 50%, between 50% and 100%, between 50% and 90%, between 50% and 80%, between 50% and 70%, between 50% and 60%, between 60% and 100%, between 60% and 90%, between 60% and 80%, between 60% and 70%, between 70% and 100%, between70% and 90%, between 70% and 80%, between 80% and 100%, between 80% and 90%, or between 90% and 100%. Circulating proinflammatory cytokine levels can be measured by any suitable methods, e.g., ELISA, western blot, RT-PCR, etc.[000109] In some embodiments, administration of an anti-HJV antibody described herein reduces local inflammation in a subject having IBD (e.g., UC, CD, IBD-U). In some embodiments, administration of an anti-HJV antibody described herein reduces local inflammation (e.g., white blood cell count, neutrophil count, lymphocyte count, levels of proinflammatory cytokines from biopsy tissues, endoscopic findings) in a subject having IBD (e.g., UC, CD, IBD-U) relative to the subject prior to administration or a subject with IBD that did not receive the administration by at least 1%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%. In some embodiments, administration of an anti-HJV antibody described herein reduces local inflammation (e.g., white blood cell count, neutrophil count, lymphocyte count, levels of proinflammatory cytokines from biopsy tissues, endoscopic findings) in the subject relative to the subject prior to administration or to a subject with IBD that did not receive the administration, by between 1% and 100%, between 5% and 100%, between 5% and 90%, between 5% and 80%, between 5% and 70%, between 5% and 60%, between 5% and 50%, between 5% and 40%, between 5% and 30%, between 5% and 20%, between 5% and 15%, between 10% and 100%, between 10% and 90%, between 10% and 80%, between 10% and 70%, between 10% and 60%, between 10% and 50%, between 10% and 40%, between 10% and 30%, between 10% and 20%, between 10% and 15%, between 20% and 100%, between 20% and 90%, between 20% and 80%, between 20% and 70%, between 20% and 60%, between 20% and 50%, between 20% and 40%, between 20% and 30%, between 30% and 100%, between 30% and 90%, between 30% and 80%, between 30% and 70%, between 30% and 60%, between 30% and 50%, between 30% and 40%, between 40% and 100%, between 40% and 90%, between 40% and 80%, between 40% and 70%, between 40% and 60%, between 40% and 50%, between 50% and 100%, between 50% and 90%, between 50% and 80%, between 50% and 70%, between 50% and 60%, between 60% and 100%, between 60% and 90%, between 60% and 80%, between 60% and 70%, between 70% and 100%, between 70% and 90%, between 70% and 80%, between 80% and 100%, between 80% and 90%, or between 90% and 100%. Local inflammation can be measured by any suitable methods, e.g., local inflammation measured by white blood cell count, neutrophil count, lymphocyte count, levels of proinflammatory cytokines from biopsy tissues, endoscopic findings, etc.[000110] In some embodiments, administration of an anti-HJV antibody described herein reduces white blood cell infiltration in the affected intestinal site in a subject having IBD (e.g., UC, CD, IBD-U) relative to the subject prior to administration or a subject with IBD that did not receive the administration by at least 1%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%. In some embodiments, administration of an anti-HJV antibody described herein reduces in a reduction of white blood cell infiltration in the affected intestinal site in the subject relative to the subject prior to administration or to a subject with IBD that did not receive the administration, by between 1% and 100%, between 5% and 100%, between 5% and 90%, between 5% and 80%, between 5% and 70%, between 5% and 60%, between 5% and 50%, between 5% and 40%, between 5% and 30%, between 5% and 20%, between 5% and 15%, between 10% and 100%, between 10% and 90%, between 10% and 80%, between 10% and 70%, between 10% and 60%, between 10% and 50%, between 10% and 40%, between 10% and 30%, between 10% and 20%, between 10% and 15%, between 20% and 100%, between 20% and 90%, between 20% and 80%, between 20% and 70%, between 20% and 60%, between 20% and 50%, between 20% and 40%, between 20% and 30%, between 30% and 100%, between 30% and 90%, between 30% and 80%, between 30% and 70%, between 30% and 60%, between 30% and 50%, between 30% and 40%, between 40% and 100%, between 40% and 90%, between 40% and 80%, between 40% and 70%, between 40% and 60%, between 40% and 50%, between 50% and 100%, between 50% and 90%, between 50% and 80%, between 50% and 70%, between 50% and 60%, between 60% and 100%, between 60% and 90%, between 60% and 80%, between 60% and 70%, between 70% and 100%, between 70% and 90%, between 70% and 80%, between 80% and 100%, between 80% and 90%, or between 90% and 100%.[000111] In some embodiments, administration of an anti-HJV antibody described herein reduces of neutrophil infiltration in the affected intestinal site in a subject having IBD (e.g., UC, CD, IBD-U) relative to the subject prior to administration or a subject with IBD that did not receive the administration by at least 1%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%. In some embodiments, administration of an anti-HJV antibody described herein reduces neutrophil infiltration in the affected intestinal site in the subject relative to the subject prior to administration or to a subject with IBD that did not receive the administration, by between 1% and 100%, between 5% and 100%, between 5% and 90%, between 5% and 80%, between 5% and 70%, between 5% and 60%, between 5% and 50%,between 5% and 40%, between 5% and 30%, between 5% and 20%, between 5% and 15%, between 10% and 100%, between 10% and 90%, between 10% and 80%, between 10% and 70%, between 10% and 60%, between 10% and 50%, between 10% and 40%, between 10% and 30%, between 10% and 20%, between 10% and 15%, between 20% and 100%, between 20% and 90%, between 20% and 80%, between 20% and 70%, between 20% and 60%, between 20% and 50%, between 20% and 40%, between 20% and 30%, between 30% and 100%, between 30% and 90%, between 30% and 80%, between 30% and 70%, between 30% and 60%, between 30% and 50%, between 30% and 40%, between 40% and 100%, between 40% and 90%, between 40% and 80%, between 40% and 70%, between 40% and 60%, between 40% and 50%, between 50% and 100%, between 50% and 90%, between 50% and 80%, between 50% and 70%, between 50% and 60%, between 60% and 100%, between 60% and 90%, between 60% and 80%, between 60% and 70%, between 70% and 100%, between 70% and 90%, between 70% and 80%, between 80% and 100%, between 80% and 90%, or between 90% and 100%.[000112] In some embodiments, administration of an anti-HJV antibody described herein reduces lymphocyte infiltration in the affected intestinal site in a subject having IBD (e.g., UC, CD, IBD-U) relative to the subject prior to administration or a subject with IBD that did not receive the administration by at least 1%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%. In some embodiments, administration of an anti-HJV antibody described herein reduces lymphocyte infiltration in the affected intestinal site in the subject relative to the subject prior to administration or to a subject with IBD that did not receive the administration, by between 1% and 100%, between 5% and 100%, between 5% and 90%, between 5% and 80%, between 5% and 70%, between 5% and 60%, between 5% and 50%, between 5% and 40%, between 5% and 30%, between 5% and 20%, between 5% and 15%, between 10% and 100%, between 10% and 90%, between 10% and 80%, between 10% and 70%, between 10% and 60%, between 10% and 50%, between 10% and 40%, between 10% and 30%, between 10% and 20%, between 10% and 15%, between 20% and 100%, between 20% and 90%, between 20% and 80%, between 20% and 70%, between 20% and 60%, between 20% and 50%, between 20% and 40%, between 20% and 30%, between 30% and 100%, between 30% and 90%, between 30% and 80%, between 30% and 70%, between 30% and 60%, between 30% and 50%, between 30% and 40%, between 40% and 100%, between 40% and 90%, between 40% and 80%, between 40% and 70%, between 40% and 60%, between 40% and 50%, between 50% and 100%, between 50% and 90%, between 50% and80%, between 50% and 70%, between 50% and 60%, between 60% and 100%, between 60% and 90%, between 60% and 80%, between 60% and 70%, between 70% and 100%, between 70% and 90%, between 70% and 80%, between 80% and 100%, between 80% and 90%, or between 90% and 100%.[000113] In some embodiments, administration of an anti-HJV antibody described herein reduces one or more proinflammatory cytokines (e.g., TNF-a, interferon y, IL-1, IL-6, IL-8, IL-17, IL-12, IL-23, IL-25, C-reactive protein (CRP) etc.) in the affected intestinal tissue or feces in a subject having IBD (e.g., UC, CD, IBD-U) relative to the subject prior to administration or a subject with IBD that did not receive the administration by at least 1%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%. In some embodiments, administration of an anti-HJV antibody described herein reduces one or more circulating proinflammatory cytokines (e.g., TNF-a, interferon y, IL-1, IL-6, IL-8, IL-17, IL-12, IL-23, IL-25, C-reactive protein (CRP) etc.) in the subject relative to the subject prior to administration or to a subject with IBD that did not receive the administration, by between 1% and 100%, between 5% and 100%, between 5% and 90%, between 5% and 80%, between 5% and 70%, between 5% and 60%, between 5% and 50%, between 5% and 40%, between 5% and 30%, between 5% and 20%, between 5% and 15%, between 10% and 100%, between 10% and 90%, between 10% and 80%, between 10% and 70%, between 10% and 60%, between 10% and 50%, between 10% and 40%, between 10% and 30%, between 10% and 20%, between 10% and 15%, between 20% and 100%, between 20% and 90%, between 20% and 80%, between 20% and 70%, between 20% and 60%, between 20% and 50%, between 20% and 40%, between 20% and 30%, between 30% and 100%, between 30% and 90%, between 30% and 80%, between 30% and 70%, between 30% and 60%, between 30% and 50%, between 30% and 40%, between 40% and 100%, between 40% and 90%, between 40% and 80%, between 40% and 70%, between 40% and 60%, between 40% and 50%, between 50% and 100%, between 50% and 90%, between 50% and 80%, between 50% and 70%, between 50% and 60%, between 60% and 100%, between 60% and 90%, between 60% and 80%, between 60% and 70%, between 70% and 100%, between 70% and 90%, between 70% and 80%, between 80% and 100%, between 80% and 90%, or between 90% and 100%.[000114] In some embodiments, administration of an anti-HJV antibody described herein improves intestinal barrier function in a subject having IBD (e.g., UC, CD, IBD-U) relative to the subject prior to administration or a subject with IBD that did not receive theadministration by at least 1%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100%. In some embodiments, administration of an anti-HJV antibody described herein improves intestinal barrier function in the subject relative to the subject prior to administration or to a subject with IBD that did not receive the administration, by between 1% and 100%, between 5% and 100%, between 5% and 90%, between 5% and 80%, between 5% and 70%, between 5% and 60%, between 5% and 50%, between 5% and 40%, between 5% and 30%, between 5% and 20%, between 5% and 15%, between 10% and 100%, between 10% and 90%, between 10% and 80%, between 10% and 70%, between 10% and 60%, between 10% and 50%, between 10% and 40%, between 10% and 30%, between 10% and 20%, between 10% and 15%, between 20% and 100%, between 20% and 90%, between 20% and 80%, between 20% and 70%, between 20% and 60%, between 20% and 50%, between 20% and 40%, between 20% and 30%, between 30% and 100%, between 30% and 90%, between 30% and 80%, between 30% and 70%, between 30% and 60%, between 30% and 50%, between 30% and 40%, between 40% and 100%, between 40% and 90%, between 40% and 80%, between 40% and 70%, between 40% and 60%, between 40% and 50%, between 50% and 100%, between 50% and 90%, between 50% and 80%, between 50% and 70%, between 50% and 60%, between 60% and 100%, between 60% and 90%, between 60% and 80%, between 60% and 70%, between 70% and 100%, between 70% and 90%, between 70% and 80%, between 80% and 100%, between 80% and 90%, or between 90% and 100%. Intestinal barrier function can be measured using any suitable method, e.g., gut permeability test.[000115] In some embodiments, a subject having IBD (e.g., UC, CD, IBD-U) has increased level of C-reactive protein (CRP) in the blood or stool, wherein the severity of IBD increases with increasing CRP level. Generally, a normal CRP level is within the range of about 1 to about 10 mg / L. In some embodiments, a subject’s CRP level is determined (e.g., prior to treatment with an anti-HJV antibody) and compared to post-treatment CRP level in the subject. In some embodiments, after administration of an anti-HJV antibody, the subject’s CRP level decreases by between 1% and 100%, between 5% and 100%, between 5% and 90%, between 5% and 80%, between 5% and 70%, between 5% and 60%, between 5% and 50%, between 5% and 40%, between 5% and 30%, between 5% and 20%, between 5% and 15%, between 10% and 100%, between 10% and 90%, between 10% and 80%, between 10% and 70%, between 10% and 60%, between 10% and 50%, between 10% and 40%, between 10% and 30%, between 10% and 20%, between 10% and 15%, between 20% and 100%, between 20% and 90%, between 20% and 80%, between 20% and 70%, between 20% and60%, between 20% and 50%, between 20% and 40%, between 20% and 30%, between 30% and 100%, between 30% and 90%, between 30% and 80%, between 30% and 70%, between 30% and 60%, between 30% and 50%, between 30% and 40%, between 40% and 100%, between 40% and 90%, between 40% and 80%, between 40% and 70%, between 40% and 60%, between 40% and 50%, between 50% and 100%, between 50% and 90%, between 50% and 80%, between 50% and 70%, between 50% and 60%, between 60% and 100%, between 60% and 90%, between 60% and 80%, between 60% and 70%, between 70% and 100%, between 70% and 90%, between 70% and 80%, between 80% and 100%, between 80% and 90%, or between 90% and 100% compared to before administration. In some embodiments, a subject with active IBD (e.g., active UC, active CD, or active IBD-U) has a c-reactive protein (CRP) level of >5mg / dL.[000116] In some embodiments, a subject having IBD (e.g., UC, CD, IBD-U) has decreased level of serum albumin, wherein the severity of IBD (e.g., UC, CD, IBD-U) increases with decreasing serum albumin concentrations. Generally, a normal concentration of serum albumin is within the range of about 3.5 g / dL to about 5.0 g / dL. In some embodiments, a subject’s serum albumin is determined (e.g., prior to treatment with an anti-HJV antibody) and compared to post-treatment serum albumin in the subject. In some embodiments, after treatment with an anti-HJV antibody, a subject’s serum albumin concentration increases by between 1% and 100%, between 5% and 100%, between 5% and 90%, between 5% and 80%, between 5% and 70%, between 5% and 60%, between 5% and 50%, between 5% and 40%, between 5% and 30%, between 5% and 20%, between 5% and 15%, between 10% and 100%, between 10% and 90%, between 10% and 80%, between 10% and 70%, between 10% and 60%, between 10% and 50%, between 10% and 40%, between 10% and 30%, between 10% and 20%, between 10% and 15%, between 20% and 100%, between 20% and 90%, between 20% and 80%, between 20% and 70%, between 20% and 60%, between 20% and 50%, between 20% and 40%, between 20% and 30%, between 30% and 100%, between 30% and 90%, between 30% and 80%, between 30% and 70%, between 30% and 60%, between 30% and 50%, between 30% and 40%, between 40% and 100%, between 40% and 90%, between 40% and 80%, between 40% and 70%, between 40% and 60%, between 40% and 50%, between 50% and 100%, between 50% and 90%, between 50% and 80%, between 50% and 70%, between 50% and 60%, between 60% and 100%, between 60% and 90%, between 60% and 80%, between 60% and 70%, between 70% and 100%, between 70% and 90%, between 70% and 80%, between 80% and 100%, between 80% and 90%, or between 90% and 100% compared to before administration.[000117] In some embodiments, a subject having IBD (e.g., UC, CD, IBD-U) has increased level of erythrocyte sedimentation rate, wherein the severity of IBD increases with increasing erythrocyte sedimentation rate. Generally, a normal erythrocyte sedimentation rate is within the range of about 0 mm / h to about 15 mm / h for adult men, and about 0 mm / h to about 20 mm / h for adult women. In some embodiments, a subject’s erythrocyte sedimentation rate is determined (e.g., prior to treatment with an anti-HJV antibody) and compared to posttreatment erythrocyte sedimentation rate in the subject. In some embodiments, after administration of an anti-HJV antibody, the subject’s erythrocyte sedimentation rate decreases by between 1% and 100%, between 5% and 100%, between 5% and 90%, between 5% and 80%, between 5% and 70%, between 5% and 60%, between 5% and 50%, between 5% and 40%, between 5% and 30%, between 5% and 20%, between 5% and 15%, between 10% and 100%, between 10% and 90%, between 10% and 80%, between 10% and 70%, between 10% and 60%, between 10% and 50%, between 10% and 40%, between 10% and 30%, between 10% and 20%, between 10% and 15%, between 20% and 100%, between 20% and 90%, between 20% and 80%, between 20% and 70%, between 20% and 60%, between 20% and 50%, between 20% and 40%, between 20% and 30%, between 30% and 100%, between 30% and 90%, between 30% and 80%, between 30% and 70%, between 30% and 60%, between 30% and 50%, between 30% and 40%, between 40% and 100%, between 40% and 90%, between 40% and 80%, between 40% and 70%, between 40% and 60%, between 40% and 50%, between 50% and 100%, between 50% and 90%, between 50% and 80%, between 50% and 70%, between 50% and 60%, between 60% and 100%, between 60% and 90%, between 60% and 80%, between 60% and 70%, between 70% and 100%, between 70% and 90%, between 70% and 80%, between 80% and 100%, between 80% and 90%, or between 90% and 100% compared to before administration.[000118] In some embodiments, a subject having IBD (e.g., UC, CD, IBD-U) has an increased erythropoietin level relative to a healthy subject. Generally, a normal erythropoietin level is within the range of about 10-30mU / mL for adults, but this value can increase individuals with severe anemia (e.g., IBD with anemia). In some embodiments, a subject having IBD has an erythropoietin higher than 30mU / mL prior to treatment with an anti-HJV antibody. In some embodiments, a subject’s erythropoietin level is determined (e.g., prior to treatment with an anti-HJV antibody) and compared to post-treatment erythropoietin level in the subject. In some embodiments, after administration of an anti-HJV antibody, the subject’s erythropoietin level decreases by between 1% and 1000%, between 100% and 1000%, between 200% and 1000%, between 300% and 1000%, between 400% and 1000%, between500% and 1000%, between 600% and 1000%, between 700% and 1000%, between 800% and 1000%, between 900% and 1000%, 100% and 900%, between 200% and 900%, between 300% and 900%, between 400% and 900%, between 500% and 900%, between 600% and 900%, between 700% and 900%, between 800% and 900%, 100% and 800%, between 200% and 800%, between 300% and 800%, between 400% and 800%, between 500% and 800%, between 600% and 800%, between 700% and 800%, 100% and 700%, between 200% and 700%, between 300% and 700%, between 400% and 700%, between 500% and 700%, between 600% and 700%, 100% and 600%, between 200% and 600%, between 300% and 600%, between 400% and 600%, between 500% and 600%, 100% and 500%, between 200% and 500%, between 300% and 500%, between 400% and 500%, 100% and 400%, between 200% and 400%, between 300% and 400%, 100% and 300%, between 200% and 300%, between 100% and 200%, between 1 and 100%, between 5% and 100%, between 5% and 90%, between 5% and 80%, between 5% and 70%, between 5% and 60%, between 5% and 50%, between 5% and 40%, between 5% and 30%, between 5% and 20%, between 5% and 15%, between 10% and 100%, between 10% and 90%, between 10% and 80%, between 10% and 70%, between 10% and 60%, between 10% and 50%, between 10% and 40%, between 10% and 30%, between 10% and 20%, between 10% and 15%, between 20% and 100%, between 20% and 90%, between 20% and 80%, between 20% and 70%, between 20% and 60%, between 20% and 50%, between 20% and 40%, between 20% and 30%, between 30% and 100%, between 30% and 90%, between 30% and 80%, between 30% and 70%, between 30% and 60%, between 30% and 50%, between 30% and 40%, between 40% and 100%, between 40% and 90%, between 40% and 80%, between 40% and 70%, between 40% and 60%, between 40% and 50%, between 50% and 100%, between 50% and 90%, between 50% and 80%, between 50% and 70%, between 50% and 60%, between 60% and 100%, between 60% and 90%, between 60% and 80%, between 60% and 70%, between 70% and 100%, between 70% and 90%, between 70% and 80%, between 80% and 100%, between 80% and 90%, or between 90% and 100% compared to before administration.[000119] In some embodiments, a subject having IBD (e.g., UC, CD, IBD-U) has increased level of fecal calprotectin (FCP), wherein the severity of IBD increases with increasing levels of fecal calprotectin. Generally, a normal fecal calprotectin level is below about 50 pg / g. In some embodiments, a subject’s fecal calprotectin level is determined (e.g., prior to treatment with an anti-HJV antibody) and compared to post-treatment fecal calprotectin level in the subject. In some embodiments, after administration of an anti-HJV antibody, the subject’s fecal calprotectin level decreases by between 1% and 100%, between 5% and 100%, between5% and 90%, between 5% and 80%, between 5% and 70%, between 5% and 60%, between 5% and 50%, between 5% and 40%, between 5% and 30%, between 5% and 20%, between 5% and 15%, between 10% and 100%, between 10% and 90%, between 10% and 80%, between 10% and 70%, between 10% and 60%, between 10% and 50%, between 10% and 40%, between 10% and 30%, between 10% and 20%, between 10% and 15%, between 20% and 100%, between 20% and 90%, between 20% and 80%, between 20% and 70%, between 20% and 60%, between 20% and 50%, between 20% and 40%, between 20% and 30%, between 30% and 100%, between 30% and 90%, between 30% and 80%, between 30% and 70%, between 30% and 60%, between 30% and 50%, between 30% and 40%, between 40% and 100%, between 40% and 90%, between 40% and 80%, between 40% and 70%, between 40% and 60%, between 40% and 50%, between 50% and 100%, between 50% and 90%, between 50% and 80%, between 50% and 70%, between 50% and 60%, between 60% and 100%, between 60% and 90%, between 60% and 80%, between 60% and 70%, between 70% and 100%, between 70% and 90%, between 70% and 80%, between 80% and 100%, between 80% and 90%, or between 90% and 100% compared to before administration. In some embodiments, a subject with active IBD (e.g., active UC, CD, or IBD-U) has a fecal calprotectin (FCP) level of >150mg / kg.[000120] In some embodiments, a subject having IBD (e.g., UC, CD, IBD-U) experiences anemia. In some embodiments, a therapeutic effect comprises treating anemia (e.g., anemia associated with IBD (e.g., UC, CD, IBD-U)) in the subject. Anemia may be assessed using any known scale or metric in the art for example, the Functional Assessment of Cancer Therapy-Anemia (FACT-An) scale (Celia, D. (1997). The Functional Assessment of Cancer Therapy-Anemia (FACT-An) Scale: a new tool for the assessment of outcomes in cancer anemia and fatigue. In Seminars in hematology (Vol. 34, No. 3 Suppl 2, pp. 13-19)). In some embodiments, the administration modulates levels of hematological parameters associated with iron status and anemia, such modulation include but are not limited to increasing hemoglobin (Hgb), increasing red blood cell levels, increasing hematocrit levels, decreasing soluble transferrin receptor levels, decreasing sTfR / log ferritin index, increasing level of transferrin saturation (TSAT%), increasing serum iron level, decreasing ferritin, reducing hepcidin levels or activity, increasing circulating hemoglobin levels, increasing reticulocytes hemoglobin (CHr), decreasing total iron binding capacity (TIBC), decreasing zinc protoporphyrin (ZPP) levels. In some embodiments, the administration improves other markers of hematological recovery (e.g., recovery of erythropoiesis, mean corpuscular hemoglobin (MCH), etc.).[000121] In some embodiments, a subject having IBD (e.g., UC, CD, IBD-U) has decreased levels of hemoglobin (Hgb) relative to healthy subjects (e.g., <12g / dL for female subjects, <13g / dL for male subjects). In some embodiments, a subject having IBD and decreased hemoglobin levels has anemia associated with IBD. In some embodiments, the severity of IBD increases with decreasing levels of Hgb. Generally, a normal hemoglobin level is between about 12 g / dL and about 18 g / dL. In some embodiments, a subject having IBD (e.g., UC, CD, IBD-U) has a level of HGB of less than 12g / dL. In some embodiments, a subject’s hemoglobin level is determined (e.g., prior to treatment with an anti-HJV antibody) and compared to post-treatment Hgb level in the subject. In some embodiments, after administration of an anti-HJV antibody, the subject’s Hgb level increases by between 1% and 100%, between 5% and 100%, between 5% and 90%, between 5% and 80%, between 5% and 70%, between 5% and 60%, between 5% and 50%, between 5% and 40%, between 5% and 30%, between 5% and 20%, between 5% and 15%, between 10% and 100%, between 10% and 90%, between 10% and 80%, between 10% and 70%, between 10% and 60%, between 10% and 50%, between 10% and 40%, between 10% and 30%, between 10% and 20%, between 10% and 15%, between 20% and 100%, between 20% and 90%, between 20% and 80%, between 20% and 70%, between 20% and 60%, between 20% and 50%, between 20% and 40%, between 20% and 30%, between 30% and 100%, between 30% and 90%, between 30% and 80%, between 30% and 70%, between 30% and 60%, between 30% and 50%, between 30% and 40%, between 40% and 100%, between 40% and 90%, between 40% and 80%, between 40% and 70%, between 40% and 60%, between 40% and 50%, between 50% and 100%, between 50% and 90%, between 50% and 80%, between 50% and 70%, between 50% and 60%, between 60% and 100%, between 60% and 90%, between 60% and 80%, between 60% and 70%, between 70% and 100%, between 70% and 90%, between 70% and 80%, between 80% and 100%, between 80% and 90%, or between 90% and 100% compared to before administration. In some embodiments, after administration of an anti-HJV antibody, the subject’s Hgb level increases by more than 100% compared to before administration. In some embodiments, after administration of an anti-HJV antibody, a subject’s Hgb level increases by at least Ig / dL. In some embodiments, after administration of an anti-HJV antibody, a subject’s HGB level increases by at least l.Og / dL, at least l. lg / dL, at least 1.2g / dL, at least 1.3g / dL, at least 1.4g / dL, at least 1.5g / dL, at least 1.6g / dL, at least 1.7g / dL, at least 1.8g / dL, at least 1.9g / dL, 2.0g / dL, at least 2.1g / dL, at least 2.2g / dL, at least 2.3g / dL, at least 2.4g / dL, at least 2.5g / dL, at least 2.6g / dL, at least 2.7g / dL, at least 2.8g / dL, at least 2.9g / dL, at least 3.0g / dL or more compared to before administration.[000122] In some embodiments, a subject having IBD (e.g., UC, CD, IBD-U) has decreased level of red blood cells. In some embodiments, an IBD subject having decreases level of red blood cells has anemia associated with IBD. In some embodiments, the severity of IBD increases with decreasing red blood cell count. Generally, a normal red blood cell count is between about 4 million cells / gL and about 5.5 million cells / gL. In some embodiments, a subject’s red blood cell count is determined (e.g., prior to treatment with an anti-HJV antibody) and compared to post-treatment red blood cell count in the subject. In some embodiments, after administration of an anti-HJV antibody, the subject’s red blood cell count increases by between 1% and 100%, between 5% and 100%, between 5% and 90%, between 5% and 80%, between 5% and 70%, between 5% and 60%, between 5% and 50%, between 5% and 40%, between 5% and 30%, between 5% and 20%, between 5% and 15%, between 10% and 100%, between 10% and 90%, between 10% and 80%, between 10% and 70%, between 10% and 60%, between 10% and 50%, between 10% and 40%, between 10% and 30%, between 10% and 20%, between 10% and 15%, between 20% and 100%, between 20% and 90%, between 20% and 80%, between 20% and 70%, between 20% and 60%, between 20% and 50%, between 20% and 40%, between 20% and 30%, between 30% and 100%, between 30% and 90%, between 30% and 80%, between 30% and 70%, between 30% and 60%, between 30% and 50%, between 30% and 40%, between 40% and 100%, between 40% and 90%, between 40% and 80%, between 40% and 70%, between 40% and 60%, between 40% and 50%, between 50% and 100%, between 50% and 90%, between 50% and 80%, between 50% and 70%, between 50% and 60%, between 60% and 100%, between 60% and 90%, between 60% and 80%, between 60% and 70%, between 70% and 100%, between 70% and 90%, between 70% and 80%, between 80% and 100%, between 80% and 90%, or between 90% and 100% compared to before administration. In some embodiments, after administration of an anti-HJV antibody, the subject’s level of red blood cells increases by more than 100% compared to before administration.[000123] In some embodiments, a subject having IBD (e.g., UC, CD, IBD-U) has decreased blood hematocrit (i.e., HCT; proportion of blood that is cellular). In some embodiments, a subject having IBD has decreased HCT. In some embodiments, an IBD subject having decreases HCT has anemia associated with IBD. In some embodiments, the severity of IBD increases with decreasing levels of hematocrit. Generally, a normal hematocrit level is between about 37% and about 52%. In some embodiments, a subject’s hematocrit level is determined (e.g., prior to treatment with an anti-HJV antibody) and compared to posttreatment hematocrit level in the subject. In some embodiments, after administration of ananti-HJV antibody, the subject’s hematocrit level increases by between 1% and 100%, between 5% and 100%, between 5% and 90%, between 5% and 80%, between 5% and 70%, between 5% and 60%, between 5% and 50%, between 5% and 40%, between 5% and 30%, between 5% and 20%, between 5% and 15%, between 10% and 100%, between 10% and 90%, between 10% and 80%, between 10% and 70%, between 10% and 60%, between 10% and 50%, between 10% and 40%, between 10% and 30%, between 10% and 20%, between 10% and 15%, between 20% and 100%, between 20% and 90%, between 20% and 80%, between 20% and 70%, between 20% and 60%, between 20% and 50%, between 20% and 40%, between 20% and 30%, between 30% and 100%, between 30% and 90%, between 30% and 80%, between 30% and 70%, between 30% and 60%, between 30% and 50%, between 30% and 40%, between 40% and 100%, between 40% and 90%, between 40% and 80%, between 40% and 70%, between 40% and 60%, between 40% and 50%, between 50% and 100%, between 50% and 90%, between 50% and 80%, between 50% and 70%, between 50% and 60%, between 60% and 100%, between 60% and 90%, between 60% and 80%, between 60% and 70%, between 70% and 100%, between 70% and 90%, between 70% and 80%, between 80% and 100%, between 80% and 90%, or between 90% and 100% compared to before administration. In some embodiments, after administration of an anti-HJV antibody, the subject’s HCT level increases by more than 100% (e.g., at least 2-fold, at least 3 -fold, at least 5-fold, at least 10-fold, at least 20-fold, at least 50-fold, at least 100-fold, at least 500- fold, at least 1000-fold, or more) compared to before administration.[000124] In some embodiments, a subject having IBD (e.g., UC, CD, IBD-U) has increased soluble transferrin receptor levels. Soluble transferrin receptor (sTfR) is a peptide cleaved from transferrin receptor 1, a receptor required for iron import into cells; levels of sTfR are commonly used as a measure of transferrin receptor 1 and functional iron status. In some embodiments, an IBD subject having high sTfR levels has anemia associated with IBD. In some embodiments, the severity of IBD increases with increasing levels of sTfR. Generally, healthy subjects have an sTfR level between 1.15-2.75mg / L. In some embodiments, a subject’s sTfR level is determined (e.g., prior to treatment with an anti-HJV antibody) and compared to post-treatment sTfR level in the subject. In some embodiments, after administration of an anti-HJV antibody, the subject’s sTfR level decreases by between 1% and 100%, between 5% and 100%, between 5% and 90%, between 5% and 80%, between 5% and 70%, between 5% and 60%, between 5% and 50%, between 5% and 40%, between 5% and 30%, between 5% and 20%, between 5% and 15%, between 10% and 100%, between 10% and 90%, between 10% and 80%, between 10% and 70%, between 10% and 60%,between 10% and 50%, between 10% and 40%, between 10% and 30%, between 10% and 20%, between 10% and 15%, between 20% and 100%, between 20% and 90%, between 20% and 80%, between 20% and 70%, between 20% and 60%, between 20% and 50%, between 20% and 40%, between 20% and 30%, between 30% and 100%, between 30% and 90%, between 30% and 80%, between 30% and 70%, between 30% and 60%, between 30% and 50%, between 30% and 40%, between 40% and 100%, between 40% and 90%, between 40% and 80%, between 40% and 70%, between 40% and 60%, between 40% and 50%, between 50% and 100%, between 50% and 90%, between 50% and 80%, between 50% and 70%, between 50% and 60%, between 60% and 100%, between 60% and 90%, between 60% and 80%, between 60% and 70%, between 70% and 100%, between 70% and 90%, between 70% and 80%, between 80% and 100%, between 80% and 90%, or between 90% and 100% compared to before administration.[000125] In some embodiments, a subject having IBD (e.g., UC, CD, IBD-U) has increased sTfR / log ferritin index (tfR-F index). The TfR-F index has been shown to be useful for differentiating between anemia from confounding factors (e.g., increased sTfR as a result of inflammation instead of reduced iron stores; see: Miicke, V., et al. (2016). Diagnosis and treatment of anemia in patients with inflammatory bowel disease. Annals of gastroenterology: quarterly publication of the Hellenic Society of Gastroenterology, 30(1), 15.). Accordingly, tfR-F index may be useful for IBD subjects in an active phase of IBD. In some embodiments, an IBD subject having high tfR-index has anemia associated with IBD. In some embodiments, the severity of IBD increases with increasing levels of tfR-index. Generally, healthy subjects have an sTfR level between 0.63-1.8. In some embodiments, a subject’s tfR-index is determined (e.g., prior to treatment with an anti-HJV antibody) and compared to post-treatment tfR-index in the subject. In some embodiments, after administration of an anti-HJV antibody, the subject’s tfR-index decreases by between 1% and 100%, between 5% and 100%, between 5% and 90%, between 5% and 80%, between 5% and 70%, between 5% and 60%, between 5% and 50%, between 5% and 40%, between 5% and 30%, between 5% and 20%, between 5% and 15%, between 10% and 100%, between 10% and 90%, between 10% and 80%, between 10% and 70%, between 10% and 60%, between 10% and 50%, between 10% and 40%, between 10% and 30%, between 10% and 20%, between 10% and 15%, between 20% and 100%, between 20% and 90%, between 20% and 80%, between 20% and 70%, between 20% and 60%, between 20% and 50%, between 20% and 40%, between 20% and 30%, between 30% and 100%, between 30% and 90%, between 30% and 80%, between 30% and 70%, between 30% and 60%, between 30% and 50%,between 30% and 40%, between 40% and 100%, between 40% and 90%, between 40% and 80%, between 40% and 70%, between 40% and 60%, between 40% and 50%, between 50% and 100%, between 50% and 90%, between 50% and 80%, between 50% and 70%, between 50% and 60%, between 60% and 100%, between 60% and 90%, between 60% and 80%, between 60% and 70%, between 70% and 100%, between 70% and 90%, between 70% and 80%, between 80% and 100%, between 80% and 90%, or between 90% and 100% compared to before administration.[000126] In some embodiments, a subject having IBD (e.g., UC, CD, IBD-U) has decreased transferrin saturation percentage (TSAT%) (i.e., a measure of the amount of iron in the blood that is bound to transferrin). In some embodiments, an IBD subject having decreased TSAT% levels has anemia associated with IBD. In some embodiments, the severity of IBD increases with decreasing levels of TSAT%. Generally, a normal TSAT% is between about 20% to about 50%. In some embodiments, a subject’s TSAT% is determined (e.g., prior to treatment with an anti-HJV antibody) and compared to post-treatment TSAT% in the subject. In some embodiments, after administration of an anti-HJV antibody, the subject’s TSAT% increases by between 1% and 100%, between 5% and 100%, between 5% and 90%, between 5% and 80%, between 5% and 70%, between 5% and 60%, between 5% and 50%, between 5% and 40%, between 5% and 30%, between 5% and 20%, between 5% and 15%, between 10% and 100%, between 10% and 90%, between 10% and 80%, between 10% and 70%, between 10% and 60%, between 10% and 50%, between 10% and 40%, between 10% and 30%, between 10% and 20%, between 10% and 15%, between 20% and 100%, between 20% and 90%, between 20% and 80%, between 20% and 70%, between 20% and 60%, between 20% and 50%, between 20% and 40%, between 20% and 30%, between 30% and 100%, between 30% and 90%, between 30% and 80%, between 30% and 70%, between 30% and 60%, between 30% and 50%, between 30% and 40%, between 40% and 100%, between 40% and 90%, between 40% and 80%, between 40% and 70%, between 40% and 60%, between 40% and 50%, between 50% and 100%, between 50% and 90%, between 50% and 80%, between 50% and 70%, between 50% and 60%, between 60% and 100%, between 60% and 90%, between 60% and 80%, between 60% and 70%, between 70% and 100%, between 70% and 90%, between 70% and 80%, between 80% and 100%, between 80% and 90%, or between 90% and 100% compared to before administration. In some embodiments, after administration of an anti-HJV antibody, the subject’s TSAT% increases by more than 100% (e.g., at least 2- fold, at least 3-fold, at least 5-fold, at least 10-fold, at least 20-fold, at least 50-fold, at least 100-fold, at least 500-fold, at least 1000-fold, or more) compared to before administration.[000127] In some embodiments, a subject having IBD (e.g., UC, CD, IBD-U) has decreased serum iron levels. In some embodiments, an IBD subject having decreased iron levels has anemia associated with IBD. In some embodiments, the severity of IBD increases with decreasing levels of serum iron. Generally, a normal level of serum iron is between about 60 pg / dL and about 170 pg / dL. In some embodiments, a subject’s serum iron level is determined (e.g., prior to treatment with an anti-HJV antibody) and compared to post-treatment serum iron level in the subject. In some embodiments, after administration of an anti-HJV antibody, the subject’s serum iron level increases by between 1% and 100%, between 5% and 100%, between 5% and 90%, between 5% and 80%, between 5% and 70%, between 5% and 60%, between 5% and 50%, between 5% and 40%, between 5% and 30%, between 5% and 20%, between 5% and 15%, between 10% and 100%, between 10% and 90%, between 10% and 80%, between 10% and 70%, between 10% and 60%, between 10% and 50%, between 10% and 40%, between 10% and 30%, between 10% and 20%, between 10% and 15%, between 20% and 100%, between 20% and 90%, between 20% and 80%, between 20% and 70%, between 20% and 60%, between 20% and 50%, between 20% and 40%, between 20% and 30%, between 30% and 100%, between 30% and 90%, between 30% and 80%, between 30% and 70%, between 30% and 60%, between 30% and 50%, between 30% and 40%, between 40% and 100%, between 40% and 90%, between 40% and 80%, between 40% and 70%, between 40% and 60%, between 40% and 50%, between 50% and 100%, between 50% and 90%, between 50% and 80%, between 50% and 70%, between 50% and 60%, between 60% and 100%, between 60% and 90%, between 60% and 80%, between 60% and 70%, between 70% and 100%, between 70% and 90%, between 70% and 80%, between 80% and 100%, between 80% and 90%, or between 90% and 100% compared to before administration. In some embodiments, after administration of an anti-HJV antibody, the subject’s serum iron level increases by more than 100% (e.g., at least 2-fold, at least 3-fold, at least 5-fold, at least 10-fold, at least 20-fold, at least 50-fold, at least 100-fold, at least 500-fold, at least 1000- fold, or more) compared to before administration.[000128] In some embodiments, a subject having IBD (e.g., UC, CD, IBD-U) has anemia and an elevated level of serum ferritin relative to healthy subjects. In some embodiments, a subject having IBD and having elevated serum ferritin levels has anemia associated with IBD. In some embodiments, the severity of IBD increases with increasing levels of serum ferritin. The normal range of serum ferritin is 24-336pg / L for man, and 11-307 pg / L for women. In some embodiments, a subject having IBD (e.g., UC, CD, IBD-U) has a level of serum ferritin level of >75pg / L. In some embodiments, a subject’s serum ferritin level isdetermined (e.g., prior to treatment with an anti-HJV antibody) and compared to posttreatment ferritin level in the subject. In some embodiments, after administration of an anti- HJV antibody, the subject’s serum ferritin level increases by between 1% and 100%, between 5% and 100%, between 5% and 90%, between 5% and 80%, between 5% and 70%, between 5% and 60%, between 5% and 50%, between 5% and 40%, between 5% and 30%, between 5% and 20%, between 5% and 15%, between 10% and 100%, between 10% and 90%, between 10% and 80%, between 10% and 70%, between 10% and 60%, between 10% and 50%, between 10% and 40%, between 10% and 30%, between 10% and 20%, between 10% and 15%, between 20% and 100%, between 20% and 90%, between 20% and 80%, between 20% and 70%, between 20% and 60%, between 20% and 50%, between 20% and 40%, between 20% and 30%, between 30% and 100%, between 30% and 90%, between 30% and 80%, between 30% and 70%, between 30% and 60%, between 30% and 50%, between 30% and 40%, between 40% and 100%, between 40% and 90%, between 40% and 80%, between 40% and 70%, between 40% and 60%, between 40% and 50%, between 50% and 100%, between 50% and 90%, between 50% and 80%, between 50% and 70%, between 50% and 60%, between 60% and 100%, between 60% and 90%, between 60% and 80%, between 60% and 70%, between 70% and 100%, between 70% and 90%, between 70% and 80%, between 80% and 100%, between 80% and 90%, or between 90% and 100% compared to before administration.[000129] In some embodiments, a subject having IBD (e.g., UC, CD, IBD-U) has an elevated level of serum hepcidin relative to healthy subjects. In some embodiments, a subject having IBD and having elevated serum hepcidin levels has anemia associated with IBD. In some embodiments, the severity of IBD increases with increasing levels of serum hepcidin. The normal range of serum hepcidin is l-55ng / mL. In some embodiments, a subject having IBD (e.g., UC, CD, IBD-U) has a level of serum hepcidin level of >55ng / mL. In some embodiments, a subject’s serum hepcidin level is determined (e.g., prior to treatment with an anti-HJV antibody) and compared to post-treatment HGB level in the subject. In some embodiments, after administration of an anti-HJV antibody, the subject’s serum hepcidin level decreases by between about 1 ng / mL and about 300 ng / mL. In some embodiments, the subject’s serum hepcidin level decreases by between about 1 ng / mL and about 200 ng / mL, between about 1 ng / mL and about 100 ng / mL, between about 1 ng / mL and about 50 ng / mL, between about 1 ng / mL and about 10 ng / mL, between about 10 ng / mL and about 100 ng / mL, or between about 10 ng / mL and about 50 ng / mL.[000130] In some embodiments, a subject having IBD (e.g., UC, CD, IBD-U) has a decreased reticulocytes hemoglobin content (CHr or RET -He). Reticulocyte hemoglobin content measures the amount of hemoglobin in reticulocytes. Generally, the normal range of CHr is about 28 to 36 pg / cell. In some embodiments, the subject has a CHr lower than the normal range. In some embodiments, the subject has a CHr less than 28 pg / ml. In some embodiments, a subject’s CHr is determined (e.g., prior to treatment with an anti-HJV antibody) and compared to post-treatment HGB level in the subject. In some embodiments, after administration of an anti-HJV antibody, the subject’s CHr increases by 1% to 100%, between 5% and 100%, between 5% and 90%, between 5% and 80%, between 5% and 70%, between 5% and 60%, between 5% and 50%, between 5% and 40%, between 5% and 30%, between 5% and 20%, between 5% and 15%, between 10% and 100%, between 10% and 90%, between 10% and 80%, between 10% and 70%, between 10% and 60%, between 10% and 50%, between 10% and 40%, between 10% and 30%, between 10% and 20%, between 10% and 15%, between 20% and 100%, between 20% and 90%, between 20% and 80%, between 20% and 70%, between 20% and 60%, between 20% and 50%, between 20% and 40%, between 20% and 30%, between 30% and 100%, between 30% and 90%, between 30% and 80%, between 30% and 70%, between 30% and 60%, between 30% and 50%, between 30% and 40%, between 40% and 100%, between 40% and 90%, between 40% and 80%, between 40% and 70%, between 40% and 60%, between 40% and 50%, between 50% and 100%, between 50% and 90%, between 50% and 80%, between 50% and 70%, between 50% and 60%, between 60% and 100%, between 60% and 90%, between 60% and 80%, between 60% and 70%, between 70% and 100%, between 70% and 90%, between 70% and 80%, between 80% and 100%, between 80% and 90%, or between 90% and 100% compared to before administration. In some embodiments, after administration of an anti-HJV antibody, the subject’s CHr increases by more than 100% (e.g., at least 2-fold, at least 3-fold, at least 5- fold, at least 10-fold, at least 20-fold, at least 50-fold, at least 100-fold, at least 500-fold, at least 1000-fold, or more) compared to before administration.[000131] In some embodiments, a subject having IBD (e.g., UC, CD, IBD-U) has increased total iron binding capacity (TIBC). Total iron binding capacity (TIBC) can be used as an indirect assessment of transferrin concentration. In individuals with iron deficiency (e.g., in IBD subjects with anemia), the relative transferrin content increases compared to iron content, resulting in high TIBC levels. In some embodiments, an IBD subject having a high TIBC has anemia associated with IBD. In some embodiments, the severity of IBD increases with increasing levels of TIBC. Generally, healthy subjects have a TIBC between 240-450mcg / dL. In some embodiments, a subject’s TIBC is determined (e.g., prior to treatment with an anti-HJV antibody) and compared to post-treatment TIBC-index in the subject. In some embodiments, after administration of an anti-HJV antibody, the subject’s TIBC-index decreases by between 1% and 100%, between 5% and 100%, between 5% and 90%, between 5% and 80%, between 5% and 70%, between 5% and 60%, between 5% and 50%, between 5% and 40%, between 5% and 30%, between 5% and 20%, between 5% and 15%, between 10% and 100%, between 10% and 90%, between 10% and 80%, between 10% and 70%, between 10% and 60%, between 10% and 50%, between 10% and 40%, between 10% and 30%, between 10% and 20%, between 10% and 15%, between 20% and 100%, between 20% and 90%, between 20% and 80%, between 20% and 70%, between 20% and 60%, between 20% and 50%, between 20% and 40%, between 20% and 30%, between 30% and 100%, between 30% and 90%, between 30% and 80%, between 30% and 70%, between 30% and 60%, between 30% and 50%, between 30% and 40%, between 40% and 100%, between 40% and 90%, between 40% and 80%, between 40% and 70%, between 40% and 60%, between 40% and 50%, between 50% and 100%, between 50% and 90%, between 50% and 80%, between 50% and 70%, between 50% and 60%, between 60% and 100%, between 60% and 90%, between 60% and 80%, between 60% and 70%, between 70% and 100%, between 70% and 90%, between 70% and 80%, between 80% and 100%, between 80% and 90%, or between 90% and 100% compared to before administration. In some embodiments, after administration of an anti-HJV antibody, the subject’s TIBC increases by more than 100% (e.g., at least 2-fold, at least 3-fold, at least 5-fold, at least 10-fold, at least 20-fold, at least 50-fold, at least 100-fold, at least 500-fold, at least 1000-fold, or more) compared to before administration.[000132] In some embodiments, a subject having IBD (e.g., UC, CD, IBD-U) has an increased zinc protoporphyrin (ZPP) level (see:, e.g., Leventi, Eleni, et al. "Zinc protoporphyrin is a reliable marker of functional iron deficiency in patients with inflammatory bowel disease." Diagnostics 11.2 (2021): 366.). Zinc protoporphyrin (ZPP) refers to the end product of zinc incorporation into protoporphyrin IX (PPIX). In healthy subjects, PPIX typically incorporates iron during erythropoiesis to produce heme; however, when iron availability is low, zinc is incorporated instead, resulting in ZPP. Accordingly, ZPP can provide a measure of iron status during erythropoiesis, and may be a useful marker of iron deficiency (e.g., in IBD subjects with anemia). In some embodiments, an IBD subject having high ZPP levels has anemia associated with IBD. In some embodiments, the severity of IBD increases with increasing levels of ZPP. Generally, healthy subjects have a ZPP levelof less than 80 pmol / mol heme. In some embodiments, a subject’s ZPP level is determined (e.g., prior to treatment with an anti-HJV antibody) and compared to post-treatment ZPP level in the subject. In some embodiments, after administration of an anti-HJV antibody, the subject’s ZPP level decreases by between 1% and 100%, between 5% and 100%, between 5% and 90%, between 5% and 80%, between 5% and 70%, between 5% and 60%, between 5% and 50%, between 5% and 40%, between 5% and 30%, between 5% and 20%, between 5% and 15%, between 10% and 100%, between 10% and 90%, between 10% and 80%, between 10% and 70%, between 10% and 60%, between 10% and 50%, between 10% and 40%, between 10% and 30%, between 10% and 20%, between 10% and 15%, between 20% and 100%, between 20% and 90%, between 20% and 80%, between 20% and 70%, between 20% and 60%, between 20% and 50%, between 20% and 40%, between 20% and 30%, between 30% and 100%, between 30% and 90%, between 30% and 80%, between 30% and 70%, between 30% and 60%, between 30% and 50%, between 30% and 40%, between 40% and 100%, between 40% and 90%, between 40% and 80%, between 40% and 70%, between 40% and 60%, between 40% and 50%, between 50% and 100%, between 50% and 90%, between 50% and 80%, between 50% and 70%, between 50% and 60%, between 60% and 100%, between 60% and 90%, between 60% and 80%, between 60% and 70%, between 70% and 100%, between 70% and 90%, between 70% and 80%, between 80% and 100%, between 80% and 90%, or between 90% and 100% compared to before administration.[000133] In some embodiments, a subject having severe IBD (e.g., UC, CD, IBD-U) as described here require hospitalization. In some embodiments, administration of an anti-HJV antibody reduces the frequency of hospitalization associated with severe IBD (e.g., UC, CD, IBD-U) by between 1% and 100%, between 5% and 100%, between 5% and 90%, between 5% and 80%, between 5% and 70%, between 5% and 60%, between 5% and 50%, between 5% and 40%, between 5% and 30%, between 5% and 20%, between 5% and 15%, between 10% and 100%, between 10% and 90%, between 10% and 80%, between 10% and 70%, between 10% and 60%, between 10% and 50%, between 10% and 40%, between 10% and 30%, between 10% and 20%, between 10% and 15%, between 20% and 100%, between 20% and 90%, between 20% and 80%, between 20% and 70%, between 20% and 60%, between 20% and 50%, between 20% and 40%, between 20% and 30%, between 30% and 100%, between 30% and 90%, between 30% and 80%, between 30% and 70%, between 30% and 60%, between 30% and 50%, between 30% and 40%, between 40% and 100%, between 40% and 90%, between 40% and 80%, between 40% and 70%, between 40% and 60%, between 40% and 50%, between 50% and 100%, between 50% and 90%, between 50% and 80%,between 50% and 70%, between 50% and 60%, between 60% and 100%, between 60% and 90%, between 60% and 80%, between 60% and 70%, between 70% and 100%, between 70% and 90%, between 70% and 80%, between 80% and 100%, between 80% and 90%, or between 90% and 100% relative to the frequency of hospitalization in the subject prior to the administration or to a subject not receiving the administration.[000134] In some embodiments, a subject with IBD does not have increased serum iron. In some embodiments, a subject with IBD does not have a condition or disease that induces iron overload (e.g., hereditary hemochromatosis). i. Ulcerative Colitis[000135] In some embodiments, the condition associated with barrier dysfunction is Ulcerative Colitis. Ulcerative Colitis (UC) is a relapsing and remitting IBD characterized by mucosal inflammation, which starts distally and can extend proximally to involve the entire colon. In some embodiments, the subject has uncreative colitis (UC). Ulcerative colitis most commonly presents as bloody diarrhea with or without mucus. Patients commonly describe tenesmus (i.e., a sensation of incomplete evacuation) and abdominal pain. The physical exam may reveal predominantly left lower or left upper quadrant abdominal pain. Signs of an acute abdomen, including guarding, rebound tenderness, or percussion tenderness, warrant investigation for toxic megacolon.[000136] In some embodiments, a subject with UC has intestinal mucosal inflammation. In some embodiments, intestinal mucosal inflammation presents with edema, ulcers, bleeding (e.g., bloody diarrhea with or without mucous), and / or electrolyte losses. In some embodiments, after administration with an anti-HJV antibody, the subject’s mucosal inflammation decreases compared to a subject not receiving an anti-HJV antibody. Nonlimiting methods of assessing mucosal inflammation include colonoscopy, sigmoidoscopy (e.g., flexible sigmoidoscopy), histological evaluation of biopsy, magnetic resonance enterography (MRE), computed tomography (CT) enterography, laboratory tests (e.g., C- reactive protein and Erythrocyte sedimentation rate), fecal calprotectin test, and small bowel endoscopy. In some embodiments, a subject with UC experiences tenesmus, abdominal pain, and / or pancolitis (inflammation of the entire colon). As UC becomes chronic, the colon often becomes more rigid and shortens (e.g., intestinal stricturing), leading to a loss of haustral markings and a “lead-pipe” appearance via barium enema, contrast computed tomography, or Abdominal X-ray (Pandit et cd.. “Lead-Pipe Colon” of Chronic Ulcerative Colitis onAbdominal X-Ray. Indian J Surg 83 , 1086-1087 (2021)). In some embodiments, a subject with UC has lead-pipe colon.[000137] In some embodiments, after treatment with an anti-HJV antibody, a subject does not have lead-pipe colon. In some embodiments, after treatment with an anti-HJV antibody, a subject with intestinal stricturing has improved intestinal rigidity and / or colon length. In some embodiments, after treatment with an anti-HJV antibody, a subject’s colon length increases by l%-100%, 5%-100%, 5%-90%, 5%-80%, 5%-70%, 5%-60%, 5%-50%, 5%- 40%, 5%-30%, 5%-20%, 5%-10%, 10%-100%, 10%-90%, 10%-80%, 10%-70%, 10%-60%, 10%-50%, 10%-40%, 10%-30%, 10%-20%, 20%-100%, 20%-90%, 20%-80%, 20%-70%, 20%-60%, 20%-50%, 20%-40%, 20%-30%, 30%-100%, 30%-90%, 30%-80%, 30%-70%, 30%-60%, 30%-50%, 30%-40%, 40%-100%, 40%-90%, 40%-80%, 40%-70%, 40%-60%, 40%-50%, 50%-100%, 50%-90%, 50%-80%, 50%-70%, 50%-60%, 60%-100%, 60%-90%, 60%-80%, 60%-70%, 70%-100%, 70%-90%, 70%-80%, 80%-100%, 80%-90%, or 90%- 100% compared to before administration of the anti-HJV antibody or compared to a subject not administered with an anti-HJV antibody. In some embodiments, after treatment with an anti-HJV antibody, a subject’s intestinal rigidity decreases by 1%-100%, 5%-100%, 5%-90%, 5%-80%, 5%-70%, 5%-60%, 5%-50%, 5%-40%, 5%-30%, 5%-20%, 5%-10%, 10%-100%, 10%-90%, 10%-80%, 10%-70%, 10%-60%, 10%-50%, 10%-40%, 10%-30%, 10%-20%, 20%-100%, 20%-90%, 20%-80%, 20%-70%, 20%-60%, 20%-50%, 20%-40%, 20%-30%, 30%-100%, 30%-90%, 30%-80%, 30%-70%, 30%-60%, 30%-50%, 30%-40%, 40%-100%, 40%-90%, 40%-80%, 40%-70%, 40%-60%, 40%-50%, 50%-100%, 50%-90%, 50%-80%, 50%-70%, 50%-60%, 60%-100%, 60%-90%, 60%-80%, 60%-70%, 70%-100%, 70%-90%, 70%-80%, 80%-100%, 80%-90%, or 90%-100% compared to before administration of the anti-HJV antibody or compared to a subject not administered with an anti-HJV antibody. Methods to assess intestinal rigidity and colon length are known in the art, any one of which can be used (e.g., colonoscopy, ultrasound, CT coIonography, MRI, biopsy, and histological evaluation) (see, e.g., Kawasaki et al., Cancer Imaging. 2021 Dec 7;21(66):2641; Utano et al., Jpn J Radiol. 2022;40(3):298-307).[000138] In some embodiments, a subject with UC has extraintestinal manifestations, such as arthritis, osteoporosis, kidney stones, uveitis, corneal ulcers, retinal vascular disease, psoriasis, oral Crohn’s disease, and fatigue (Levine and Burakoff, Gastroenterol Hepatol (NY). 2011 Apr;7(4):235-241). In some embodiments, an anti-HJV antibody is used to treat extraintestinal manifestations ofUC. In some embodiments, after treatment with an anti-HJV antibody, a subject has a reduction in arthritis, osteoporosis, kidney stones, uveitis, cornealulcers, retinal vascular disease, psoriasis, and / or oral Crohn’s disease. In some embodiments, after treatment with an anti-HJV antibody, a subject with UC has an improved quality of life (e.g., as assessed by a self-reporting questionnaire).[000139] In some embodiments, a subject having UC may experience fatigue (i.e., feeling of tiredness, exhaustion, burnout, or lack of energy that does not go away with usual amount of rest or sleep). In some embodiments, a subject having UC has physical fatigue (e.g., low energy or strength, or a feeling of heaviness). In some embodiments, a subject having UC has mental fatigue (e.g., low motivation, concentration, or alertness). In some embodiments, a subject having UC has both physical and mental fatigue. In some embodiments, a subject having active UC has fatigue associated with UC (i.e., flare up). In some embodiments, a subject who previously had surgery to treat UC is more susceptible to having fatigue (i.e., has higher chance of having fatigue relative to UC subject that did not have surgery). In some embodiments, a female UC subject is more susceptible to having fatigue relative to male UC subjects. In some embodiments, UC subjects who also has depression or anxiety is more susceptible to having fatigue relative to UC subjects who do not have depression or anxiety. In some embodiments, a UC subject with one or more extraintestinal manifestations is more susceptible to having fatigue relative to subjects who do not have extraintestinal manifestations. In some embodiments, fatigue is assessed via patient self-reported questionnaires, the fatigue severity scale (FSS), the visual analog scale (VAS), the numeric rating scale (NRS), the multidimensional fatigue inventory (MFI), the mental fatigue scale (MFS), the wood mental fatigue inventory (WMFI), the fatigue-assessment scale (FAS), the functional assessment of chronic illness therapy -fatigue (FACIT-F), interviews and clinical assessment, activity monitoring (e.g., wearable devices), and / or any other method known in the art (Billones et al. , Brain Behav Immun Health. 202) Aug; 15: 100266). Other non-limiting examples of methods to assess fatigue include the fatigue catastrophizing scale, the multidimensional assessment of fatigue (MAF), the revised piper fatigue scale (PFS), the checklist of individual strength (CIS), the isometric muscle strength test (physiological test of fatigue), the Manchester COPD fatigue scale, the modified fatigue impact scale, the multidimensional daily diary of fatigue-fibromyalgia- 17 (MDF-Fibro-17) instrument, the Brugmann fatigue scale (BFS), the Chalder fatigue scale, the fatigue assessment scale (FAS), the fatigue impact scale, the fatigue symptom inventory (F SI), the health assessment questionnaire (HAQ), the functional assessment of cancer therapy scale for anemia and fatigue (e.g., FACT-Anemia), and the MG fatigue scale (MGFS).[000140] In some embodiments, fatigue can be assessed by the Inflammatory Bowel Disease- Fatigue (IBD-F) patient self-assessment scale (see, e.g., Varbobitis etal., The IBD-F Patient Self-Assessment Scale Accurately Depicts the Level of Fatigue and Predicts a Negative Effect on the Quality of Life of Patients With IBD in Clinical Remission, Inflamm Bowel Dis. 2021 May 17;27(6):826-835, the contents regarding IBD-F patient self-assessment scale is incorporated herein by reference. IBD-F patient self-assessment scale is a scoring system includes two sections of questions for a subject. Score 1 is a Fatigue Assessment Scale including five questions, which measures the severity of fatigue with a scoring scale of 0-20. If a subject scored 1 or more than 1 in score 1, the subject should proceed to answer the questions in score 2. Section 2 of Fatigue Rating Scale for IBD is IBD-Fatigue impact on Daily Activities Scale, which includes 30 questions and measures the impact of fatigue to quality of life (QoL) with a scoring scale of 0-120. In some embodiments, a score 1 value more than 7.5 indicates significant fatigue (e.g., clinically significant fatigue). In some embodiments, a subject having UC with fatigue has a score 1 based on IBD-F patient selfassessment scale in the range of 7.5 to 20, 7.5 to 19, 7.5 to 18, 7.5 to 17, 7.5 to 16, 7.5 to 15, 7.5 to 14, 7.5 to 13, 7.5 to 12, 7.5 to 11, 7.5 to 10, 7.5 to 9, 7.5 to 8, 8 to 20, 8 to 19, 8 to 18, 8 to 17, 8 to 16, 8 to 15, 8 to 14, 8 to 13, 8 to 12, 8 to 11, 8 to 10, 8 to 9, 9 to 20, 9 to 19, 9 to 18, 9 to 17, 9 to 16, 9 to 15, 9 to 14, 9 to 13, 9 to 12, 9 to 11, 9 to 10, 10 to 20, 10 to 19, 10 to 18, 10 to 17, 10 to 16, 10 to 15, 10 to 14, 10 to 13, 10 to 12, 10 to 11, 11 to 20, 11 to 19, 11 to18, 11 to 17, 11 to 16, 11 to 15, 11 to 14, 11 to 13, 11 to 12, 12 to 20, 12 to 19, 12 to 18, 12 to17, 12 to 16, 12 to 15, 12 to 14, 12 to 13, 13 to 20, 13 to 19, 13 to 18, 13 to 17, 13 to 16, 13 to15, 13 to 14, 14 to 20, 14 to 19, 14 to 18, 14 to 17, 14 to 16, 14 to 15, 15 to 20, 15 to 19, 15 to18, 15 to 17, 15 to 16, 16 to 20, 16 to 19, 16 to 18, 16 to 17, 17 to 20, 17 to 19, 17 to 18, 18 to20, 18 to 19, or 19 to 20. In some embodiments, a subject having UC with fatigue affects the quality of life (QoL). In some embodiments, a subject having UC with fatigue as a score 2 based on IBD-F patient self-assessment scale in the range of 0-120, 5-120, 10-120, 20-120, 30-120, 40-120, 50-120, 60-120, 70-120, 80-120, 90-120, 100-120, 110-120, 0-110, 5-110, 10-110, 20-110, 30-110, 40-110, 50-110, 60-110, 70-110, 80-110, 90-110, 100-110, 0-100, 5- 100, 10-100, 20-100, 30-100, 40-100, 50-100, 60-100, 70-100, 80-100, 90-100, 0-90, 5-90, 10-90, 20-90, 30-90, 40-90, 50-90, 60-90, 70-90, 80-90, 0-80, 5-80, 10-80, 20-80, 30-80, 40- 80, 50-80, 60-80, 70-80, 0-70, 5-70, 10-70, 20-70, 30-70, 40-70, 50-70, 60-70, 0-60, 5-60, 10-60, 20-60, 30-60, 40-60, 50-60, 0-50, 5-50, 10-50, 20-50, 30-50, 40-50, 0-40, 5-40, 10-40, 20-40, 30-40, 0-30, 5-30, 10-30, 20-30, 0-20, 5-20, 10-20, 0-10, 5-10, or 0-5. In some embodiments, the administration reduces fatigue in the subject relative to the subject prior tothe administration or to a subject that did not receive the administration. In some embodiments, the administration reduces fatigue based on IBD-F patient self-assessment scale in the subject relative to the subject prior to the administration or to a subject that did not receive the administration. In some embodiments, the administration reduces score 1 based on IBD-F patient self-assessment scale in the subject by at least 0.5 point, by at least 1 point, by at least 2 points, by at least 2.5 points, by at least 3 points, by at least 4 points, by at least 5 points, by at least 6 points, by at least 7 points, by at least 8 points, by at least 9 points, by at least 10 points, by at least 11 points, by at least 12 points, by at least 13 points, by at least 14 points, by at least 15 points, by at least 16 points, by at least 17 points, by at least 18 points, by at least 19 points, or by at least 20 points relative to the subject prior to the administration or to a subject that did not receive the administration. In some embodiments, the administration reduces score 1 based on IBD-F patient self-assessment scale in the subject in the range of 1-2 points, 1-5 points, 1-10 points, 1-15 points, 1-20 points, 2-5 points, 2-8 points, 2-10 points, 2-12 points, 2-15 points, 2-20 points, 5-8 points, 5-10 points, 5-12 points, 5-15 points, 5-18 points, 5-20 points, 8-10 points, 8-12 points, 8-15 points, 8-18 points, 8-20 points, 10-12 points, 10-15 points, 10-18 points, 10-20 points, 12-15 points, 12-15 points, 12- 18 points, 12-20 points, 15-18 points, 15-20 points, 16-18 points, 16-20 points, or 18-20 points relative to the subject prior to the administration or to a subject that did not receive the administration. In some embodiments, the administration reduces score 2 based on IBD-F patient self-assessment scale in the subject by at by at least 1 point, by at least 5 points, by at least 10 points, by at least 15 points, by at least 25 points, by at least 25 points, by at least 30 points, by at least 40 points, by at least 50 points, by at least 60 points, by at least 70 points, by at least 80 points, by at least 90 points, by at least 100 points, by at least 110 points, or by at least 120 points relative to the subject prior to the administration or to a subject that did not receive the administration. In some embodiments, the administration reduces score 2 based on IBD-F patient self-assessment scale in the subject in the range of 1-120 points, 1-110 points, 1-100 points, 1-90 points, 1-80 points, 1-70 points, 1-60 points, 1-50 points, 1-40 points, 1-30 points, 1-20 points, 1-10 points, 1-5 points, 5-120 points, 5-110 points, 5-100 points, 5-90 points, 5-80 points, 5-70 points, 5-60 points, 5-50 points, 5-40 points, 5-30 points, 5-20 points, 5-10 points, 10-120 points, 10-110 points, 10-100 points, 10-90 points, 10-80 points, 10-70 points, 10-60 points, 10-50 points, 10-40 points, 10-30 points, 10-20 points, 20-120 points, 20-110 points, 20-100 points, 20-90 points, 20-80 points, 20-70 points, 20-60 points, 20-50 points, 20-40 points, 20-30 points, 30-120 points, 30-110 points, 30-100 points, 30-90 points, 30-80 points, 30-70 points, 30-60 points, 30-50 points, 30-40 points, 40-120 points, 40-110 points, 40-100 points, 40-90 points, 40-80 points, 40-70 points, 40-60 points, 40-50 points, 50-120 points, 50-110 points, 50-100 points, 50-90 points, 50-80 points, 50-70 points, 50-60 points, 60-120 points, 60-110 points, 60-100 points, 60-90 points, 60-80 points, 60-70 points, 70-120 points, 70-110 points, 70-100 points, 70-90 points, 70-80 points, 80-120 points, 80-110 points, 80-100 points, 80-90 points, 90-120 points, 90-110 points, 90- 100 points, 100-120 points, 100-110 points, or 110-120 points relative to the subject prior to the administration or to a subject that did not receive the administration.[000141] In some embodiments, fatigue can be assessed by the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue (FACIT-F) scale (see, e.g., Tinsley, A., Macklin, E. A., Korzenik, J. R., & Sands, B. E. (2011). Validation of the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) in patients with inflammatory bowel disease. Alimentary pharmacology & therapeutics, 34(11-12), 1328-1336; and facit.org / measures / facit-f) and / or the Functional Assessment of Cancer Therapy (FACT) Anemia (FACT-An) scale (see, e.g., Celia D. The Functional Assessment of Cancer Therapy- Anemia (FACT-An) Scale: a new tool for the assessment of outcomes in cancer anemia and fatigue. Seminars in Hematology. 1997 Jul;34(3 Suppl 2): 13-19; and facit.org / measures / fact- an). The FACIT-F scale contains 40 questions relating to 5 categories of well-being: physical well-being (7 questions), social well-being (7 questions), emotional well-being (6 questions), function well-being (7 questions), and fatigue (13 questions). The FACT-An scale contains the questions of the FACIT-F scale and an additional 7 questions relating to anemia. For both assessments, patients provide a score between 0-4 (inclusive) for each item. For each category, individual items are summed, multiplied by the number of items presented, and divided by the number of items answered to calculate a category score; for example, fatigue category scores for either FACIT-F or FACT-An can range from 0-52. Category scores are then summed to derive a total score, ranging from 0-160 for FACIT-F or 0-188 for FACT- An. Higher scores within these ranges indicate better quality of life (QoL). Typically, healthy individuals have a FACIT-F fatigue category score of 40 or greater (e.g., Celia D, Lai JS, Chang CH, Peterman A, Slavin M. Fatigue in cancer patients compared with fatigue in the general United States population. Cancer. 2002;94(2):528-38). In some embodiments, a score value of less than about 40 points in the fatigue category of the FACIT-F scale indicates significant fatigue (e.g., clinically significant fatigue). In some embodiments, a subject having UC with fatigue has a FACIT-F fatigue category score in the range of 0-40, 0-39, 0- 38, 0-37, 0-36, 0-35, 0-34, 0-33, 0-32, 0-31, 0-30, 0-29, 0-28, 0-27, 0-26, 0-25, 0-24, 0-23, 0- 22, 0-21, 0-20, 0-19, 0-18, 0-17, 0-16, 0-15, 0-14, 0-13, 0-12, 0-11, 0-10, 0-9, 0-8, 9-7, 0-6,or 0-5. In some embodiments, the administration reduces fatigue based on the FACIT-F scale in the subject relative to the subject prior to the administration or to a subject that did not receive the administration. In some embodiments, the administration increases a FACIT-F fatigue category score of the subject by at least 0.5 point, by at least 1 point, by at least 2 points, by at least 2.5 points, by at least 3 points, by at least 4 points, by at least 5 points, by at least 7 points, by at least 7 points, by at least 8 points, by at least 9 points, by at least 10 points, by at least 11 points, by at least 12 points, by at least 13 points, by at least 14 points, by at least 15 points, by at least 16 points, by at least 17 points, by at least 18 points, by at least 19 points, or by at least 20 points relative to the subject prior to the administration or to a subject that did not receive the administration. In some embodiments, the administration increases a FACIT-F fatigue category score in the subject in the range of 1-2 points, 1-5 points, 1-10 points, 1-15 points, 1-20 points, 2-5 points, 2-8 points, 2-10 points, 2-12 points, 2-15 points, 2-20 points, 5-8 points, 5-10 points, 5-12 points, 5-15 points, 5-18 points, 5-20 points, 8-10 points, 8-12 points, 8-15 points, 8-18 points, 8-20 points, 10-12 points, 10-15 points, 10-18 points, 10-20 points, 12-15 points, 12-15 points, 12-18 points, 12-20 points, 15- 18 points, 15-20 points, 16-18 points, 16-20 points, or 18-20 points relative to the subject prior to the administration or to a subject that did not receive the administration.[000142] In some embodiments, the administration improves a patient’s quality of life (QoL). In some embodiments, QoL is assessed by the Patient’s Global Impression of Change (PGL C) self-assessment (see: Hurst, Hugh, and Jennifer Bolton. "Assessing the clinical significance of change scores recorded on subjective outcome measures." Journal of manipulative and physiological therapeutics 27.1 (2004): 26-35.). The PGI-C self-assessment contains a single question related to changes in condition from the beginning of a treatment, scored on a numerical scale of 1-7. Patients scoring a 6-7 on the PGI-C scale are considered to have experienced clinically significant improvements in their condition. In some embodiments, the administration improves QoL based on the PGI-C scale in the subject relative to a subject that did not receive the administration. In some embodiments, subjects having UC and receiving the administration report a PGI-C score of 5, 6, or 7.[000143] In some embodiments, QoL is assessed by the Medical Outcomes Study Short Form 36 (SF-36) (see, e.g.: Garratt AM, Schmidt L, Mackintosh A, Fitzpatrick R. Quality of life measurement: bibliographic study of patient assessed health outcome measures. Brit Med J. 2002;324: 1417-9; Contopoulos-Ioannidis DG, Karvouni A, Kouri I, loannidis JPA. SF-36 outcomes in randomized trials: a systematic review. Brit Med J. 2009;338:a3006). The SF-36 consists of 8 subscales: 1) Physical Functioning; 2) Role Limitations due to PhysicalProblems; 3) General Health Perceptions; 4) Vitality; 5) Social Functioning; 6) Role Limitations due to Emotional Problems; 7) General Mental Health; and 8) Health Transition. Items within each subscale are totaled, multiplied by 10, and added to 50 to linearly transform each value to fit within a scale ranging from 0 (negative health) to 100 (positive health), wherein 50 represents the mean value; the transformed value is the corresponding score for each subscale. Certain subscale scores can be assessed together to generate a physical component summary (“PCS”) or mental component summary (“MCS”) based on factor analysis (e.g., Ware JE, Kosinski M, Bayliss MS, McHomey C, Rogers WH, Raczek A. Comparison of methods for scoring and statistical analysis of the SF-36 health profile and summary measures: summary of results from the Medical Outcomes Study. Med Care. 1995;33:AS264-79.). In some embodiments, the administration reduces fatigue in the subject relative to the subject prior to the administration or to a subject that did not receive the administration. In some embodiments, the administration reduces fatigue based on IBD-F patient self-assessment scale in the subject relative to the subject prior to the administration or to a subject that did not receive the administration. In some embodiments, the administration increases a subscale score of SF-36 in the subject by at least 1 point, by at least 2 points, by at least 3 points, by at least 4 points, by at least 5 points, by at least 6 points, by at least 7 points, by at least 8 points, by at least 9 points, by at least 10 points, by at least 11 points, by at least 12 points, by at least 13 points, by at least 14 points, by at least 15 points, by at least 16 points, by at least 17 points, by at least 18 points, by at least 19 points, by at least 20 points, by at least 21 points, by at least 22 points, by at least 23 points, by at least 24 points, by at least 25 points, by at least 26 points, by at least 27 points, by at least 28 points, by at least 29 points, or by at least 30 points relative to the subject prior to the administration or to a subject that did not receive the administration. In some embodiments, the administration increases a subscale score of SF-36 in the subject in the range of 1-2 points, 1-5 points, 1-10 points, 1-15 points, 1-20 points, 1-25 points, 1-30 points, 2-5 points, 2-8 points, 2-10 points, 2-12 points, 2-15 points, 2-20 points, 2-25 points, 2-30 points, 5-8 points, 5-10 points, 5-12 points, 5-15 points, 5-18 points, 5-20 points, 5-25 points, 5-30 points, 8-10 points, 8-12 points, 8-15 points, 8-18 points, 8-20 points, 8-25 points, 5-30 points, 10-12 points, 10-15 points, 10-18 points, 10-20 points, 10-25 points, 10-30 points, 12- 15 points, 12-15 points, 12-18 points, 12-20 points, 12-25 points, 12-30 points, 15-18 points, 15-20 points, 15-25 points, 15-30 points, 20-25 points, 20-30 points, or 25-30 points relative to the subject prior to the administration or to a subject that did not receive the administration. In some embodiments, the administration increases a PCS score of SF-36 inthe subject by at least 1 point, by at least 2 points, by at least 3 points, by at least 4 points, by at least 5 points, by at least 6 points, by at least 7 points, by at least 8 points, by at least 9 points, by at least 10 points, by at least 11 points, by at least 12 points, by at least 13 points, by at least 14 points, by at least 15 points, by at least 16 points, by at least 17 points, by at least 18 points, by at least 19 points, by at least 20 points, by at least 21 points, by at least 22 points, by at least 23 points, by at least 24 points, by at least 25 points, by at least 26 points, by at least 27 points, by at least 28 points, by at least 29 points, or by at least 30 points relative to the subject prior to the administration or to a subject that did not receive the administration. In some embodiments, the administration increases a PCS score of SF-36 in the subject in the range of 1-2 points, 1-5 points, 1-10 points, 1-15 points, 1-20 points, 1-25 points, 1-30 points, 2-5 points, 2-8 points, 2-10 points, 2-12 points, 2-15 points, 2-20 points, 2-25 points, 2-30 points, 5-8 points, 5-10 points, 5-12 points, 5-15 points, 5-18 points, 5-20 points, 5-25 points, 5-30 points, 8-10 points, 8-12 points, 8-15 points, 8-18 points, 8-20 points, 8-25 points, 5-30 points, 10-12 points, 10-15 points, 10-18 points, 10-20 points, 10-25 points, 10-30 points, 12-15 points, 12-15 points, 12-18 points, 12-20 points, 12-25 points, 12- 30 points, 15-18 points, 15-20 points, 15-25 points, 15-30 points, 20-25 points, 20-30 points, or 25-30 points relative to the subject prior to the administration or to a subject that did not receive the administration. In some embodiments, the administration increases a MCS score of SF-36 in the subject by at least 1 point, by at least 2 points, by at least 3 points, by at least 4 points, by at least 5 points, by at least 6 points, by at least 7 points, by at least 8 points, by at least 9 points, by at least 10 points, by at least 11 points, by at least 12 points, by at least 13 points, by at least 14 points, by at least 15 points, by at least 16 points, by at least 17 points, by at least 18 points, by at least 19 points, by at least 20 points, by at least 21 points, by at least 22 points, by at least 23 points, by at least 24 points, by at least 25 points, by at least 26 points, by at least 27 points, by at least 28 points, by at least 29 points, or by at least 30 points relative to the subject prior to the administration or to a subject that did not receive the administration. In some embodiments, the administration increases a MCS score of SF-36 in the subject in the range of 1-2 points, 1-5 points, 1-10 points, 1-15 points, 1-20 points, 1-25 points, 1-30 points, 2-5 points, 2-8 points, 2-10 points, 2-12 points, 2-15 points, 2-20 points, 2-25 points, 2-30 points, 5-8 points, 5-10 points, 5-12 points, 5-15 points, 5-18 points, 5-20 points, 5-25 points, 5-30 points, 8-10 points, 8-12 points, 8-15 points, 8-18 points, 8-20 points, 8-25 points, 5-30 points, 10-12 points, 10-15 points, 10-18 points, 10-20 points, 10-25 points, 10-30 points, 12-15 points, 12-15 points, 12-18 points, 12-20 points, 12-25 points, 12- 30 points, 15-18 points, 15-20 points, 15-25 points, 15-30 points, 20-25 points, 20-30 points,or 25-30 points relative to the subject prior to the administration or to a subject that did not receive the administration.[000144] The etiology of UC involves interactions between the environment, immune system, gut microbiome, and genetic predisposition (Kobayashi et al., Nat Rev Dis Primers. 2020 Sep 10;6(l):74). In some embodiments, severity of UC is assessed using the Truelove and Richards Index (Truelove and Richards, BrMedJ. 1956 Jun 9; 1 (4979):

[1315] -l 318, 1322-2), the Gomes index (Gomes et aL, Gut. 1986 Jan;27(l):92-95), the Riley score (Riley et aL, Gut. 1991 Feb;32(2): 174-178), the Geboes Score (Geboes et al., Gut. 2000 Sep; 47(3):404- 409), the Harpaz / Mount Sinai Index (Fiel et al, Modern Pathology. 2003 ;83 (1): 118A), the Modified Riley Score (Feagan et al. , N Eng J Med. 2005 Jun 16;352(24):2499-507), the Chicago / Rubin / Histologic inflammation Activity Scale (Rubin et al, In Gasteroenterol. 2007 Apr 1; 134(4): A19-A19), the Modified Harpaz Index (Theede et al., Clin Gastroenterol Hepatol. 2015 Nov;13(l l): 1929-36.31), the Simplified Geboes Score (Jauregui-Amezaga et al., J Crohns Colitis. 2017 Mar 1;11 (3):305-313), the Nancy Index (Marchal-Bressenot et al., Gut. 2017 Jan;66(l):43-49), the Robarts Histopathology Score (Hosli et al., Gut. 2017 Jan;66(l):50-58). In some embodiments, UC patients are classified using MRI imaging. In some embodiments, subjects with UC are classified using the Montreal classification system (Satsangi et al., Gut. 2006 Jun;55(6):749-753) and / or the Truelove-Witts criteria (Truelove and Witts, BrMedJ. 1955 Oct 29;2(4947): 1041-8). In some embodiments, UC severity is classified as mild, moderate, or severe. In some embodiments, UC severity is classified as mild, moderate-to-severe, or fulminant (Pabla et al., Gastroenterol Clin North Am. 2020 Dec;49(4):671-688).[000145] In some embodiments, the term “disease activity” with reference to UC refers to a cross-sectional, moment-in-time assessment of inflammation. In some embodiments, the term “disease severity” with reference to UC refers to longitudinal and historical factors of a patient, such as prior biologic failure, history of maximum disease extent, and health care use metrics such as hospitalization and disability scoring tools. In some embodiments, disease severity of IBD is assessed by (1) impact of disease on the patient (e.g., clinical symptoms, patient-reported outcomes, quality of life, and disability); (2) inflammatory burden (e.g., extent, location, and severity of bowel involvement at a given time); and (3) disease course, including structural damage (Peyrin-Biroulet et al., Clin Gastroenterol Hepatol. 2016 Mar;14(3):348-354.el7). Besides disease extent, the main risk factors for colorectal cancer in UC include disease duration, active inflammation (endoscopic or histological), presence of strictures, presence of post-inflammatory polyps, family history of colorectal cancer, andassociated primary sclerosing cholangitis. An intestinal stricture refers to a narrowing or constriction of the intestinal lumen. In some embodiments, administration of an anti-HJV antibody prevents or treats an intestinal stricture. In some embodiments, an anti-HJV antibody prevents the development of colorectal cancer associated with UC. In some embodiments, treatment with an anti-HJV antibody reduces the need for hospitalization in a subject with UC. In some embodiments, a subject administered with an anti-HJV antibody is hospitalized less frequently compared to a subject that is not administered with an anti-HJV antibody.[000146] In some embodiments, a subject with UC is currently taking or has taken another therapy for the treatment of UC and / or its associated symptoms. In some embodiments, a subject with UC is unresponsive to another therapy for the treatment of UC and / or its associated symptoms. In some embodiments, a subject with UC is unable to tolerate treatment with another therapy for the treatment of UC and / or its associated symptoms. As used herein, “another therapy” refers to a therapy that is not an HJV antagonist. Non-limiting examples of UC therapies include aminosalicylates (5-ASA), corticosteroids, sphingosine 1- phosphate receptor modulators (e.g., Estrasimod, Ozanimod), immunomodulators (e.g., Azathioprine, 6-mercaptopurine, Cyclosporine, or Tacrolimus), Janus kinase (JAK) inhibitors (e.g., Upadacitinib, Tofacitinib), tumor necrosis factor (TNF) inhibitors (e.g., adalimumab, Certolizumab pegol, Infliximab, Golimumab), integrin antagonists (e.g., natalizumab, Vedolizumab), interleukin (IL)-23 antagonists (e.g., Risankizumab-rzaa), or IL-12 / IL23 antagonists (e.g., Ustekinumab), nicotine, Sulfasalazine (e.g., Azulfidine, Salazopyrin, Sulazine), Mesalamine (e.g., Delzicol, Canasa, Asacol HD, Sfrowasa, Apriso, Lialda, Pentasa), Olsalazine, Balsalazide, or Azathioprine. In some embodiments, a subject with UC is currently taking or has taken a corticosteroid for the treatment of UC and / or its associated symptoms. In some embodiments, a subject with US is unresponsive to corticosteroids for the treatment of UC and / or its associated symptoms. In some embodiments, a subject with UC is unable to tolerate corticosteroids for the treatment of UC and / or its associated symptoms. Non-limiting examples of corticosteroids for the treatment of UC include hydrocortisone, Prednisone (e.g., Prednisone Intensol, Deltasone, Rayos), Methylprednisolone (e.g., Depo- Medrol, Medrol, Solu-Medrol, P-Care D80, ReadySharp Methylprednisolone, P-Care D40), Prednisolone (e.g., Omnipred, Pred Mild, Pred Forte, Orapred ODT, Millipred DP, Veripred 20, Pediapred), and Budenoside (e.g., Entocort, Uceris, Rhinocort Allergy, Pulmicort Flexhaler, Pulmicort). In some embodiments, a subject is currently taking or has taken atopical corticosteroid as an acute therapy of distal colitis. In some embodiments, an anti-HJV antibody reduces the need for corticosteroid use in a subject with UC.[000147] In some embodiments, an anti-HJV antibody is used to promote and / or maintain remission of UC in a subject. In some embodiments, severity and remission are assessed by a patient-reported outcome (PRO). In some embodiments, a PRO is a patient questionnaire, such as a questionnaire assessing quality of life and validated symptom scores. In some embodiments, severity and remission are assessed by the resolution of clinical UC symptoms. In some embodiments, remission comprises reduction or cessation of rectal bleeding. In some embodiments, remission comprises improvement in bowel habits (e.g., stool frequency). In some embodiments, remission comprises endoscopic healing. In some embodiments, remission in a subject is assessed by an activity index, such as the Mayo Score, Seo Index, Rachmilewitz Index, Simple Clinical Colitis Activity Index (SCCAI), PRO2, or the Pediatric UC Activity Index (PUCAI) (Rubin et al., Am. J of Gastroenterol. 2019 Mar;l 14(3): 384- 413).[000148] In some embodiments, UC severity and remission is assessed by Disease Activity Index (DAI). In some embodiments, the DAI used to assess UC severity and remission is the Ulcerative Colitis Endoscopic Index of Severity (UCEIS). The UCEIS scoring system for assessment of ulcerative colitis severity ranges from 0-8, with higher scores indicating more severe disease. The score is the sum of 3 subscores: (1) vascular pattern (scored 0-2); (2) bleeding (scored 0-3); and erosions and ulcers (scored 0-3) (Ikeya etal., J Grohns Colitis. 2016 Mar;10(3):286-295). In some embodiments, a subject with a UCEIS score of 5-8 has severe UC. In some embodiments, a subject with a UCEIS score of 2-4 has mild-to-moderate UC. In some embodiments, a subject with a UCEIS score of 0-1 is in remission. In some embodiments, UC remission is indicated by a UCEIS score of 1. In some embodiments, UC remission is indicated by a UCEIS score of 0. In some embodiments, a subject is said to be in UC remission if no individual UCEIS subscore is greater than 1. In some embodiments, a subject is said to be in UC remission if no individual subscore is greater than 0.[000149] In some embodiments, the DAI used to assess UC severity and remission is the Mayo score (i.e., Mayo disease activity index) (Ungaro et al., Lancet. 2017 Apr 29;389(10080): 1756-1770). The Mayo scoring system for assessment of ulcerative colitis activity ranges from 0-12, with higher scores indicating more severe disease. The score is the sum of 4 subscores: (1) stool frequency; (2) rectal bleeding; (3) endoscopy; and (4) physician’s global assessment, each of which ranges from 0 (normal) to 3 (severe disease) (Rutgeerts et al., N Engl J Med 2005;353:2462-2476). In some embodiments, a subject with aMayo score of 8-12 has severe UC. In some embodiments, a subject with a Mayo score of 5-7 has moderate UC. In some embodiments, a subject with a Mayo score of 2-4 has mild UC. In some embodiments, UC remission is indicated by a Mayo score of 2. In some embodiments, UC remission is indicated by a Mayo score of 1. In some embodiments, UC remission is indicated by a Mayo score of 0. In some embodiments, a subject is said to be in UC remission if no individual Mayo subscore is greater than 1. In some embodiments, a subject is said to be in UC remission if no individual Mayo subscore is greater than 0. In some embodiments, a subject is said to be in UC remission if each individual Mayo subscore is 0 or 1.[000150] In some embodiments, the DAI used to assess UC severity and remission is the Partial Mayo Score (PMS) (i.e., Mayo score without endoscopy). PMS ranges from 0 (normal or inactive disease) to 9 (severe disease) and is calculated as the sum of 3 subscores (stool frequency, rectal bleeding, and physician’s global assessment), each of which ranges from 0 (normal) to 3 (severe disease). In some embodiments, a subject with a PMS of 7-9 has severe UC. In some embodiments, a subject with a PMS of 5-6 (inclusive) has moderate disease. In some embodiments, a subject with a PMS of 2-4 (inclusive) has mild disease. In some embodiments, a subject with a PMS of 1 is in UC remission. In some embodiments, a subject with a PMS of 0 is in UC remission. In some embodiments, a subject is said to be in UC remission if no individual PMS subscore is greater than 1. In some embodiments, a subject is said to be in UC remission if no individual PMS subscore is greater than 0. In some embodiments, a subject is said to be in UC remission if each individual PMS subscore is 0 or 1.[000151] In some embodiments, the DAI used to assess UC severity and remission is the Ulcerative Colitis Colonoscopic Index of Severity (UCCIS) (Samuel et al., Clin Gastroenterol Hepatol. 2013 Jan; 1 l(l):49-54.31). The UCCIS scoring system for assessment of ulcerative colitis severity includes subscores based on: vascular pattern (0-2), granularity (0-2), erosions / ulcers (0-4), bleeding friability (0-2), segmental endoscopic severity (4-point scale), and global endoscopic severity (4-point scale and a 10-cm visual analog scale). A higher UCCIS score indicates more severe disease.[000152] In some embodiments, an HJV antagonist (e.g., an anti-HJV antibody) reduces the severity of UC. In some embodiments, an HJV antagonist (e.g., an anti-HJV antibody) maintains remission of UC. In some embodiments, administration of an anti-HJV antibody reduces a subject’s UCEIS classification from severe (i.e., UCEIS score of 5-8) to mild-to- moderate (i.e., UCEIS score of 2-4). In some embodiments, administration of an anti-HJV antibody reduces a subject’s UCEIS classification from severe (i.e., UCEIS score of 5-8) toremission (i.e., UCEIS score of 0 or 1). In some embodiments, administration of an anti-HJV antibody reduces a subject’s UCEIS classification from mild-to-moderate (i.e., UCEIS score of 2-4) to remission (i.e., UCEIS score of 0 or 1). In some embodiments, administration of an anti-HJV antibody maintains a subject’s UCEIS classification at remission (i.e., UCEIS score of 0 or 1) after administration.[000153] In some embodiments, administration of an anti-HJV antibody reduces a subject’s Mayo score classification from severe (i.e., Mayo score of 8-12) to moderate (i.e., Mayo score of 5-7). In some embodiments, administration of an anti-HJV antibody reduces a subject’s Mayo score classification from severe (i.e., Mayo score of 8-12) to mild (i.e., Mayo score of 2-4). In some embodiments, administration of an anti-HJV antibody reduces a subject’s Mayo score classification from severe (i.e., Mayo score of 8-12) to remission (i.e., Mayo score of 0 or 1). In some embodiments, administration of an anti-HJV antibody reduces a subject’s Mayo score classification from moderate (i.e., Mayo score of 5-7) to mild (i.e., Mayo score of 2-4). In some embodiments, administration of an anti-HJV antibody reduces a subject’s Mayo score classification from mild (i.e., Mayo score of 2-4) to remission (i.e., Mayo score of 0 or 1). In some embodiments, administration of an anti-HJV antibody reduces a subject’s Mayo score classification from mild (i.e., Mayo score of 2-4) to remission (i.e., Mayo score of 0 or 1). In some embodiments, administration of an anti-HJV antibody maintains a subject’s Mayo score classification at remission (i.e., Mayo score of 0 or 1) after administration.[000154] In some embodiments, administration of an anti-HJV antibody reduces a subject’s PMS classification from severe (i.e., PMS of 7-9) to moderate (i.e., PMS of 5-6). In some embodiments, administration of an anti-HJV antibody reduces a subject’s PMS classification from severe (i.e., PMS of 7-9) to mild (i.e., PMS of 2-4). In some embodiments, administration of an anti-HJV antibody reduces a subject’s PMS classification from severe (i.e., PMS of 7-9) to remission (i.e., PMS of 0 or 1). In some embodiments, administration of an anti-HJV antibody reduces a subject’s PMS classification from moderate (i.e., PMS of 5- 6) to mild (i.e., PMS of 2-4). In some embodiments, administration of an anti-HJV antibody reduces a subject’s PMS classification from moderate (i.e., PMS of 5-6) to remission (i.e., PMS of 0 or 1). In some embodiments, administration of an anti-HJV antibody reduces a subject’s PMS classification from mild (i.e., PMS of 2-4) to remission (i.e., PMS of 0 or 1). In some embodiments, administration of an anti-HJV antibody maintains a subject’s PMS classification at remission (i.e., PMS of 0 or 1) after administration.[000155] As used herein, the term “remission” encompasses clinical remission, endoscopic remission, histologic remission, biomarker-based (e.g., biochemical) remission, radiological remission, and patient-reported remission. In some embodiments, radiological remission is assessed by imaging studies (e.g., CT or MRI) to evaluate inflammation in the intestinal tract (Shaban et al., Gastroenterol. 2022;13:e28-e34). In some embodiments, patient-reported remission (e.g., Manitoba IBD Index (MIBDI)) is used to assess overall remission (Clara et al.. Am J Gastroenterol. 2009 Ju; 104(7): 1754-63). In some embodiments, patient-reported outcomes encompass quality of life, overall well-being, and the ability to perform daily activities. In some embodiments, patient-reported remission is evaluated through a patient questionnaire. In some embodiments, biomarker-based (i.e., biochemical) remission is based on the measurement of biomarkers of inflammation (e.g., C-reactive protein) (Kessel etal., Sci Rep. 2021 Mar 23; 11 :6690). In some embodiments, inflammatory biomarkers can be used to assess the level of inflammation in the body, and low or normal levels of these biomarkers indicate remission.[000156] In some embodiments, clinical remission comprises the absence or significant reduction of clinical symptoms associated with IBD, such as abdominal pain, diarrhea, fatigue, weight loss, and rectal bleeding (Vuitton et al.. Aliment Pharmacol Ther. 2017 Mar;45(6):801-813). In some embodiments, after administration of an anti-HJV antibody, a subject has decreased abdominal pain, decreased diarrhea, decreased fatigue, decreased weight loss, and / or decreased rectal bleeding compared to before administration of the anti- HJV antibody or compared to a subject not administered with an anti-HJV antibody. In some embodiments, clinical remission is assessed through patient-reported outcomes. In some embodiments, clinical remission is evaluated using the clinical activity index (CAI), which comprises 7 items: stool frequency (0-3); blood in stool (0-4); general well-being (0-3); abdominal discomfort (0-3); fever (0-3); extra-intestinal manifestations (0-9); and laboratory findings (erythrocyte sedimentation rate and hemoglobin) (0-4) (Rachmilewitz D, BMJ. 1989 Jan 14;298(6666):82-6), wherein a higher CAI score indicates more severe disease. In some embodiments, clinical remission is defined as a CAI of < 3. In some embodiments, after administration of an anti-HJV antibody to a subject with UC, the CAI score of a subject decreases by the range of l%-100%, 5%-100%, 5%-90%, 5%-80%, 5%-70%, 5%-60%, 5%- 50%, 5%-40%, 5%-30%, 5%-20%, 5%-10%, 10%-100%, 10%-90%, 10%-80%, 10%-70%, 10%-60%, 10%-50%, 10%-40%, 10%-30%, 10%-20%, 20%-100%, 20%-90%, 20%-80%, 20%-70%, 20%-60%, 20%-50%, 20%-40%, 20%-30%, 30%-100%, 30%-90%, 30%-80%, 30%-70%, 30%-60%, 30%-50%, 30%-40%, 40%-100%, 40%-90%, 40%-80%, 40%-70%,40%-60%, 40%-50%, 50%-100%, 50%-90%, 50%-80%, 50%-70%, 50%-60%, 60%-100%, 60%-90%, 60%-80%, 60%-70%, 70%-100%, 70%-90%, 70%-80%, 80%-100%, 80%-90%, or 90%-100% relative to the subject prior to administration or to a subject that did not receive the administration.[000157] In some embodiments, UC severity (e.g., remission) is assessed via endoscopy. In some embodiments, endoscopic remission is assessed via endoscopic index. Non-limiting examples of endoscopic indices include the Baron Score (Baron et al., BrMed J. 1964 Jan 11 ; 1 (5375): 89-91), Rachmilewitz Index (also known as CAI, described above), Ulcerative Colitis Endoscopic Index of Severity, Mayo Clinic Endoscopic Subscore, and Ulcerative Colitis Colonoscopic Index of Severity. In some embodiments, endoscopic remission is assessed via endoscopy by presence of edema, loss of vascularity, erythema, mucosal granularity and friability, erythema, erosions, and ulcers, and pseudopolyps (Spiceland and Lodhia, World J Gastroenterol. 2018 Sep 21;24(35):4014-4020). In some embodiments, endoscopic remission is determined by examining the mucosal lining of the digestive tract using endoscopy (Kim KO, Clin Endosc. 2022 Jul;55(4):480-4). In some embodiments, remission (e.g., endoscopic remission) is indicated by mucosal healing. In some embodiments, mucosal healing is characterized by the reduction or absence of intestinal erythematous mucosa, friability, blood, erosions, ulcers, or other signs of inflammation of the intestinal tract (D’Haens et al., Gastroenterol. 2007 Feb;132(2):763-86). In some embodiments, mucosal healing is characterized by the absence of all mucosal ulceration, both microscopic and macroscopic, providing a sigmoidoscopy score of 0, as assessed by the Ulcerative Colitis Disease Activity Index (Lichtenstein and Rutgeerts, Inflamm Bowel Dis. 2010 Feb;16(2):338-46). In some embodiments, the absence of visible signs of intestinal inflammation indicates endoscopic remission and / or mucosal healing. In some embodiments, signs of improvement in the appearance of the mucosa indicate endoscopic remission and / or mucosal healing. In some embodiments, the improvement of intestinal vascular patterns indicates endoscopic remission and / or mucosal healing. In some embodiments, a decrease in intestinal erosion and / or ulcers indicates endoscopic remission and / or mucosal healing. In some embodiments, a decrease in intestinal (e.g., colon) bleeding indicates endoscopic remission and / or mucosal healing. In some embodiments, a decrease in intestinal erythematous mucosa indicates endoscopic remission and / or mucosal healing. In some embodiments, administration of an anti-HJV antibody promotes mucosal healing in a subject. In some embodiments, after administration of an anti-HJV antibody to a subject with UC, the endoscopic index decreases by the range of 1%- 100%, 5%-100%, 5%-90%, 5%-80%, 5%-70%, 5%-60%, 5%-50%, 5%-40%, 5%-30%, 5%-20%, 5%-10%, 10%-100%, 10%-90%, 10%-80%, 10%-70%, 10%-60%, 10%-50%, 10%-40%, 10%-30%, 10%-20%, 20%-100%, 20%-90%, 20%-80%, 20%-70%, 20%-60%, 20%-50%, 20%-40%, 20%-30%, 30%-100%, 30%-90%, 30%-80%, 30%-70%, 30%-60%, 30%-50%, 30%-40%, 40%-100%, 40%-90%, 40%-80%, 40%-70%, 40%-60%, 40%-50%, 50%-100%, 50%-90%, 50%-80%, 50%-70%, 50%-60%, 60%-100%, 60%-90%, 60%-80%, 60%-70%, 70%-100%, 70%-90%, 70%-80%, 80%-100%, 80%-90%, or 90%-100% relative to the subject prior to administration or to a subject that did not receive the administration, (e.g., as assessed by any of the indices described above or any other suitable methods). In some embodiments, after administration of an anti-HJV antibody to a subject with UC, the subject has improved intestinal vascular patterns, decreased intestinal erosion, decreased intestinal ulcers, decreased intestinal bleeding, decreased intestinal erythematous mucosa, and / or decreased intestinal friability compared to before administration of the anti-HJV antibody or compared to a subject not administered with the anti-HJV antibody.[000158] In some embodiments, histologic remission (also referred to as “histologic improvement” or “histologic healing”) is based on microscopic examination of tissue samples (i.e., biopsies) taken during endoscopy (Bryant et al., J Crohns Colitis. 2014 Dec;8(12): 1582- 97). In some embodiments, even when the mucosa appears normal via endoscopy, histologic remission requires confirmation at the cellular level to indicate the absence of microscopic inflammation. Non-limiting examples of methods to assess histologic remission include study designs by Truelove and Richards (Truelove and Richards, Br Med J. 1956;1 : 1315-1318), Riley et al. (Riley et al., Gut. 1991;32: 174-178), Geboes etal., (Geboes etal., Gut.2000;47:404-409), Floren et al., (Floren et al., Scand J Gastroenterol. 1987;22:459-462), Hanauer et al. , (Hanauer et al., Am J Gastroenterol. 1993;88:1188-1197; Hanauer et al. , Gastroenterology. 1998;115:525-532), and Gupta et al. (Gupta et al., Gastroenterology. 2007;133: 1099-1105). In some embodiments, histologic improvement is assessed by structural architecture of the intestine, chronic inflammatory cell infiltrate, surface epithelial integrity, mucin depletion, crypt abscesses or distortion, gland enhancement, gland and mucosal atrophy, fulminant inflammation, neutrophils in the epithelium, lamina propria neutrophils and eosinophils, crypt destruction, and / or erosion or ulceration (Peyrin-Biroulet et al., Clin Gastroenterol Hepatol. 2014 Jun;12(6):929-34.e2).[000159] In some embodiments, after administration of an anti-HJV antibody to a subject, the subject has improved structural architecture of the intestine, decreased chronic inflammatory cell infiltrate, increased surface epithelial integrity, decreased mucin depletion, decreasedcrypt abscesses or distortion, decreased gland and mucosal atrophy, decreased fulminant inflammation, decreased neutrophils in the epithelium, decreased lamina propria neutrophils and eosinophils, decreased crypt destruction, and / or decreased intestinal erosion or ulceration compared to before administration of the anti-HJV antibody or compared to a subject not administered with an anti-HJV antibody (e.g., as assessed by any of the methods described above or known in the art).[000160] In some embodiments, an anti-HJV antibody promotes remission in a subject if the Mayo score of said subject is reduced by at least 1%, at least 2%, at least 3%, at least 4%, at least 5%, at least 6%, at least 7%, at least 8%, at least 9%, at least 10%, at least 11%, at least 12%, at least 13%, at least 14%, at least 15%, at least 16%, at least 17%, at least 18%, at least 19%, at least 20%, at least 22%, at least 24%, at least 26%, at least 28%, at least 30%, at least 32.5%, at least 35%, at least 37.5%, at least 40%, at least 42.5%, at least 45%, at least 47.5%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% from baseline following the administration of the anti-HJV antibody. In some embodiments, an anti-HJV antibody promotes remission in a subject if the Mayo score of said subject is reduced by the range of 1%- 100%, 5%-100%, 5%-90%, 5%-80%, 5%-70%, 5%-60%, 5%-50%, 5%-40%, 5%-30%, 5%-20%, 5%-10%, 10%-100%, 10%-90%, 10%-80%, 10%-70%, 10%-60%, 10%-50%, 10%-40%, 10%-30%, 10%-20%, 20%-100%, 20%-90%, 20%-80%, 20%-70%, 20%-60%, 20%-50%, 20%-40%, 20%-30%, 30%-100%, 30%-90%, 30%-80%, 30%-70%, 30%-60%, 30%-50%, 30%-40%, 40%-100%, 40%-90%, 40%-80%, 40%-70%, 40%-60%, 40%-50%, 50%-100%, 50%-90%, 50%-80%, 50%-70%, 50%-60%, 60%-100%, 60%-90%, 60%-80%, 60%-70%, 70%-100%, 70%-90%, 70%-80%, 80%-100%, 80%-90%, or 90%-100% relative to the subject prior to administration or to a subject that did not receive the administration.[000161] In some embodiments, an anti-HJV antibody promotes remission in a subject if the Mayo score of said subject decreases by at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, or 12 from baseline following the administration of the anti-HJV antibody. In some embodiments, an anti-HJV antibody promotes remission in a subject if the Mayo score of said subject decreases by the range of 1- 12, 1-11, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, 1-2, 2-12, 2-11, 2-10, 2-9, 2-8, 2-7, 2-6, 2-5, 2-4, 2-3, 3-12, 3-11, 3-10, 3-9, 3-8, 3-7, 3-6, 3-5, 3-4, 4-12, 4-11, 4-10, 4-9, 4-8, 4-7, 4-6, 4-5, 5-12, 5-11, 5-10, 5-9, 5-8, 5-7, 5-6, 6-12, 6-11, 6-10, 6-9, 6-8, 6-7, 7-12, 7-11, 7-10, 7-9, 7-8, 8-12, 8-11, 8-10, 8-9, 9-12, 9-11, 9-10, 10-12, 10-11, or 11-12 relative to the subject prior to administration or to a subject that did not receive the administration.[000162] In some embodiments, an anti-HJV antibody promotes remission in a subject with UC (e.g., with a Mayo score of > 2) if the Mayo score of said subject is in the range of 0-1 or1-2 following administration of the anti-HJV antibody in said subject.[000163] In some embodiments, an anti-HJV antibody promotes remission in a subject if the PMS of said subject is reduced by at least 1%, at least 2%, at least 3%, at least 4%, at least 5%, at least 6%, at least 7%, at least 8%, at least 9%, at least 10%, at least 11%, at least 12%, at least 13%, at least 14%, at least 15%, at least 16%, at least 17%, at least 18%, at least 19%, at least 20%, at least 22%, at least 24%, at least 26%, at least 28%, at least 30%, at least 32.5%, at least 35%, at least 37.5%, at least 40%, at least 42.5%, at least 45%, at least 47.5%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% from baseline following the administration of the anti-HJV antibody. In some embodiments, an anti-HJV antibody promotes remission in a subject if the PMS of said subject is reduced by the range of 1%- 100%, 5%-100%, 5%- 90%, 5%-80%, 5%-70%, 5%-60%, 5%-50%, 5%-40%, 5%-30%, 5%-20%, 5%-10%, 10%- 100%, 10%-90%, 10%-80%, 10%-70%, 10%-60%, 10%-50%, 10%-40%, 10%-30%, 10%- 20%, 20%-100%, 20%-90%, 20%-80%, 20%-70%, 20%-60%, 20%-50%, 20%-40%, 20%- 30%, 30%-100%, 30%-90%, 30%-80%, 30%-70%, 30%-60%, 30%-50%, 30%-40%, 40%- 100%, 40%-90%, 40%-80%, 40%-70%, 40%-60%, 40%-50%, 50%-100%, 50%-90%, 50%- 80%, 50%-70%, 50%-60%, 60%-100%, 60%-90%, 60%-80%, 60%-70%, 70%-100%, 70%- 90%, 70%-80%, 80%-100%, 80%-90%, or 90%-100% relative to the subject prior to administration or to a subject that did not receive the administration. In some embodiments, an anti-HJV antibody promotes remission in a subject if the PMS of said subject decreases by at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, or 9 from baseline following the administration of the anti-HJV antibody. In some embodiments, an anti-HJV antibody promotes remission in a subject if the PMS of said subject decreases by 0- 1, 0-2, 0-3, 0-4, 0-5, 0-6, 0-7, 0-8, 0-9, 1-2, 1-3, 1-4, 1-5, 1-6, 1-7, 1-8, 1-9, 2-3, 2-4, 2-5, 2-6,2-7, 2-8, 2-9, 3-4, 3-5, 3-6, 3-7, 3-8, 3-9, 4-5, 4-6, 4-7, 4-8, 4-9, 5-6, 5-7, 5-8, 5-9, 6-7, 6-8, 6- 9, 7-8, 7-9, or 8-9. In some embodiments, an anti-HJV antibody promotes remission in a subject with active (i.e., acute) UC (e.g., with a PMS of > 2) if the Mayo score of said subject is in the range of 0-1 or 1-2 following administration of the anti-HJV antibody in said subject. [000164] In some embodiments, an anti-HJV antibody promotes remission in a subject if a subject with acute (e.g., active) IBD (i.e., with a Mayo score of 2-12 or a PMS of 2-9) reaches remission (i.e., a Mayo score or PMS of 0 or 1) within less than 5 days, less than 6 days, less than 7 days, less than 8 days, less than 9 days, less than 10 days, less than 11 days, less than12 days, less than 13 days, less than 14 days, less than 15 days, less than 16 days, less than 17 days, less than 18 days, less than 19 days, less than 20 days, less than 22 days, less than 24 days, less than 26 days, less than 28 days, less than 30 days, less than 32 days, less than 34 days, less than 36 days, less than 38 days, less than 40 days, less than 42 days, less than 44 days, less than 46 days, less than 48 days, less than 50 days, less than 55 days, less than 60 days, less than 65 days, less than 70 days, less than 75 days, less than 80 days, less than 85 days, less than 90 days, less than 95 days, less than 100 days, less than 110 days, less than 120 days, less than 130 days, less than 140 days, less than 150 days, less than 160 days, less than 170 days, less than 180 days, less than 190 days, or less than 200 days, less than 220 days, less than 240 days, less than 260 days, less than 280 days, or less than 280 days following administration of the anti-HJV antibody. In some embodiments, an anti-HJV antibody promotes remission in a subject if a subject with active (i.e., acute) IBD (i.e., with a Mayo score of 2-12 or a PMS of 2-9) reaches remission (i.e., a Mayo score or PMS of 0 or 1) within 5-10 days, within 10-15 days, within 15-20 days, within 20-25 days, within 25-30 days, within 30-35 days, within 35-40 days, within 40-45 days, within 45-50 days, within SO- 55 days, within 55-60 days, within 60-65 days, within 65-70 days, within 70-75 days, within 75-80 days, within 80-85 days, within 85-90 days, within 90-95 days, within 95-100 days, within 100-110 days, within 110-120 days, within 120-130 days, within 130-140 days, within 140-150 days, within 150-160 days, within 160-170 days, within 170-180 days, within 180- 190 days, within 190-200 days, within 200-220 days, within 220-240 days, within 240-260 days, within 260-280 days, or within 280-300 days following administration of the anti-HJV antibody.[000165] In some embodiments, administration of an HJV antagonist (e.g., an anti-HJV antibody) maintains remission in a subject with IBD. In some embodiments, administration of an HJV antagonist (e.g., an anti-HJV antibody) maintains endoscopic remission in a subject. In some embodiments, administration of an HJV antagonist (e.g., an anti-HJV antibody) maintains clinical remission in a subject. In some embodiments, administration of an HJV antagonist (e.g., an anti-HJV antibody) maintains biomarker-based (i.e., biochemical) remission in a subject. In some embodiments, administration of an HJV antagonist (e.g., an anti-HJV antibody) maintains histologic remission in a subject. In some embodiments, administration of an HJV antagonist (e.g., an anti-HJV antibody) maintains radiological remission in a subject. In some embodiments, administration of an HJV antagonist (e.g., an anti-HJV antibody) maintains patient-reported remission in a subject.[000166] In some embodiments, administration of an HJV antagonist (e.g., an anti-HJV antibody) maintains remission in a subject with IBD. In some embodiments, administration of an HJV antagonist (e.g., an anti-HJV antibody) maintains endoscopic remission in a subject. In some embodiments, administration of an HJV antagonist (e.g., an anti-HJV antibody) maintains clinical remission in a subject. In some embodiments, administration of an HJV antagonist (e.g., an anti-HJV antibody) maintains biomarker-based (i.e., biochemical) remission in a subject. In some embodiments, administration of an HJV antagonist (e.g., an anti-HJV antibody) maintains histologic remission in a subject. In some embodiments, administration of an HJV antagonist (e.g., an anti-HJV antibody) maintains radiological remission in a subject. In some embodiments, administration of an HJV antagonist (e.g., an anti-HJV antibody) maintains patient-reported remission in a subject.[000167] In some embodiments, an HJV antagonist (e.g., an anti-HJV antibody) is said to maintain remission in a subject with IBD if said subject shows longer amounts of time spent in remission compared to a subject who is not administered an HJV antagonist. In some embodiments, an HJV antagonist (e.g., an anti-HJV antibody) is said to maintain remission in a subject with IBD if said subject shows longer amounts of time spent in remission compared to time spent in remission before being administered an HJV antagonist. In some embodiments, an anti-HJV antibody maintains remission in a subject if a subject with a Mayo score of 1 has a Mayo score of 1 after administration of the anti-HJV antibody. In some embodiments, an anti-HJV antibody maintains remission in a subject if a subject with a Mayo score of 1 has a Mayo score of 0 after administration of the anti-HJV antibody. In some embodiments, an anti-HJV antibody maintains remission in a subject if a subject with a Mayo score of 0 has a Mayo score of 1 after administration of the anti-HJV antibody. In some embodiments, an anti-HJV antibody maintains remission in a subject if a subject with a Mayo score of 0 has a Mayo score of 0 after administration of the anti-HJV antibody. In some embodiments, an anti-HJV antibody maintains remission in a subject if a subject with a Mayo score of 0-1 (inclusive) has a Mayo score of 0-1 (inclusive) after administration of the anti- HJV antibody.[000168] In some embodiments, an anti-HJV antibody maintains remission in a subject if a subject with a PMS of 1 has a PMS of 1 after administration of the anti-HJV antibody. In some embodiments, an anti-HJV antibody maintains remission in a subject if a subject with a PMS of 1 has a PMS of 0 after administration with the anti-HJV antibody. In some embodiments, an anti-HJV antibody maintains remission in a subject if a subject with a PMS of 0 has a PMS of 1 after administration with the anti-HJV antibody. In some embodiments,an anti-HJV antibody maintains remission in a subject if a subject with a PMS of 0 has a PMS of 0 after administration with the anti-HJV antibody. In some embodiments, an anti- HJV antibody maintains remission in a subject if a subject with a PMS of 0-1 (inclusive) has a PMS of 0-1 (inclusive) after administration of the anti-HJV antibody.[000169] In some embodiments, an anti-HJV antibody maintains remission in a subject if a subject with a Mayo score and / or a PMS of 0 or 1 maintains a Mayo score and / or PMS of 0 or 1 after administration of an anti-HJV antibody for at least 10 days, at least 15 days, at least 20 days, at least 30 days, at least 40 days, at least 50 days, at least 60 days, at least 70 days, at least 80 days, at least 90 days, at least 100 days, at least 110 days, at least 120 days, at least 130 days, at least 140 days, at least 150 days, at least 160 days, at least 170 days, at least 180 days, at least 190 days, at least 200 days, at least 220 days, at least 240 days, at least 260 days, at least 280 days, at least 300 days, at least 325 days, at least 350 days, at least 375 days, at least 400 days, at least 425 days, at least 450 days, at least 475 days, at least 500 days, at least 550 days, at least 600 days, at least 650 days, at least 700 days, at least 750 days, at least 800 days, at least 850 days, at least 900 days, at least 950 days, at least 1000 days, at least 1100 days, at least 1200 days, at least 1300 days, at least 1400 days, or at least 1500 days. In some embodiments, an anti-HJV antibody maintains remission in a subject if a subject with a Mayo score and / or a PMS of 0 or 1 maintains a Mayo score and / or a PMS score of 0 or 1 after administration of an anti-HJV antibody for about 10-15, about 15-20, about 20-30, about 30-40, about 40-50, about 50-60, about 60-70, about 70-80, about 80-90, about 90-100, about 100-110, about 110-120, about 120-130, about 130-140, about 140-150, about 150-160, about 160-170, about 170-180, about 180-190, about 190-200, about 200-220, about 220-240, about 240-260, about 260-280, about 280-300, about 300-325, about 325-350, about 350-375, about 375-400, about 400-425, about 425-450, about 450-475, about 475-500, about 500-550, about 550-600, about 600-650, about 650-700, about 700-750, about 750-800, about 800-850, about 850-900, about 900-950, about 950-1000, about 1000-1100, about 1100-1200, about 1200-1300, about 1300-1400, about 1400-1500, or more days.[000170] In some embodiments, a subject with a rectal bleeding subscore of 1 is in UC remission. In some embodiments, a subject with a rectal bleeding subscore of 0 is in UC remission. In some embodiments, a subject with a rectal bleeding subscore of 2 is experiencing acute (e.g., active) UC. In some embodiments, a subject with a rectal bleeding subscore of 3 is experiencing acute (e.g., active) UC. In some embodiments, an anti-HJV antibody reduces a rectal bleeding subscore by at least 1, at least 2, or 3. In some embodiments, an anti-HJV antibody reduces a rectal bleeding subscore by 0-1, 1-2, or 2-3. Insome embodiments, a subject with a baseline rectal bleeding subscore of 3 has a rectal bleeding subscore of 2 after administration of an anti-HJV antibody. In some embodiments, a subject with a baseline rectal bleeding subscore of 3 has a rectal bleeding subscore of 1 after administration of an anti-HJV antibody. In some embodiments, a subject with a rectal bleeding subscore of 3 has a rectal bleeding subscore of 0 after administration of an anti-HJV antibody. In some embodiments, a subject with a baseline rectal bleeding subscore of 2 has a rectal bleeding subscore of 1 after administration of an anti-HJV antibody. In some embodiments, a subject with a baseline rectal bleeding subscore of 2 has a rectal bleeding subscore of 0 after administration of an anti-HJV antibody. In some embodiments, a subject with a rectal bleeding subscore of 1 has a rectal bleeding subscore of 1 after administration of an anti-HJV antibody. In some embodiments, a subject with a rectal bleeding subscore of 1 has a rectal bleeding subscore of 0 after administration of an anti-HJV antibody. In some embodiments, a subject with a rectal bleeding subscore of 0 has a rectal bleeding subscore of 1 after administration with an anti-HJV antibody. In some embodiments, a subject with a rectal bleeding subscore of 0 has a rectal bleeding subscore of 0 after administration of an anti-HJV antibody.[000171] In some embodiments, a subject with a stool frequency subscore of 1 is in UC remission. In some embodiments, a subject with a stool frequency subscore of 0 is in UC remission. In some embodiments, a subject with a stool frequency subscore of 2 is experiencing acute (e.g., active) UC. In some embodiments, a subject with a stool frequency subscore of 3 is experiencing acute (e.g., active) UC. In some embodiments, an anti-HJV antibody reduces a stool frequency subscore by at least 1, at least 2, or 3. In some embodiments, an anti-HJV antibody reduces a stool frequency subscore by 0-1, 1-2, or 2-3. In some embodiments, a subject with a stool frequency subscore of 3 has a stool frequency subscore of 2 after administration of an anti-HJV antibody. In some embodiments, a subject with a stool frequency subscore of 3 has a stool frequency subscore of 1 after administration of an anti-HJV antibody. In some embodiments, a subject with a stool frequency subscore of 3 has a stool frequency subscore of 0 after administration of an anti-HJV antibody. In some embodiments, a subject with a stool frequency subscore of 2 has a stool frequency subscore of 1 after administration of an anti-HJV antibody. In some embodiments, a subject with a stool frequency subscore of 2 has a stool frequency subscore of 0 after administration of an anti-HJV antibody. In some embodiments, a subject with a stool frequency subscore of 1 has a stool frequency subscore of 1 after administration of an anti-HJV antibody. In some embodiments, a subject with a stool frequency subscore of 1 has a stool frequency subscoreof 0 after administration of an anti-HJV antibody. In some embodiments, a subject with a stool frequency subscore of 0 has a stool frequency subscore of 1 after administration of an anti-HJV antibody. In some embodiments, a subject with a stool frequency subscore of 0 has a stool frequency subscore of 0 after administration of an anti-HJV antibody.[000172] In some embodiments, a subject with a physician’s global assessment score of 1 is in UC remission. In some embodiments, a subject with a physician’s global assessment subscore of 0 is in UC remission. In some embodiments, a subject with a physician’s global assessment subscore of 2 is experiencing active (i.e., acute) UC. In some embodiments, a subject with a physician’s global subscore of 3 is experiencing active (i.e., acute) UC. In some embodiments, an anti-HJV antibody reduces a physician’s global assessment score by at least 1, at least 2, or 3. In some embodiments, an anti-HJV antibody reduces a physician’s global assessment subscore by 0-1, 1-2, or 2-3. In some embodiments, a subject with a physician’s global assessment subscore of 3 has a physician’s global assessment subscore of 2 after administration of an anti-HJV antibody. In some embodiments, a subject with a physician’s global assessment subscore of 3 has a physician’s global assessment subscore of 1 after administration of an anti-HJV antibody. In some embodiments, a subject with a physician’s global assessment subscore of 3 has a physician’s global assessment subscore of 0 after administration of an anti-HJV antibody. In some embodiments, a subject with a physician’s global assessment subscore of 2 has a physician’s global assessment subscore of 1 after administration of an anti-HJV antibody. In some embodiments, a subject with a physician’s global assessment subscore of 2 has a physician’s global assessment subscore of 0 after administration of an anti-HJV antibody. In some embodiments, a subject with a physician’s global assessment subscore of 1 has a physician’s global assessment subscore of 1 after administration of an anti-HJV antibody. In some embodiments, a subject with physician’s global assessment subscore of 1 has a physician’s global assessment subscore of 0 after administration of an anti-HJV antibody. In some embodiments, a subject with a physician’s global assessment subscore of 0 has a physician’s global assessment subscore of 1 after administration of an anti-HJV antibody. In some embodiments, a subject with a physician’s global assessment subscore of 0 has a physician’s global assessment subscore of 0 after administration of an anti-HJV antibody.[000173] In some embodiments, a subject with an endoscopy subscore (i.e., Mayo endoscopic score) of 0 is in UC remission. In some embodiments, a subject with an endoscopy subscore of 1 has mild UC. In some embodiments, a subject with an endoscopy subscore of 2 has moderate UC. In some embodiments, a subject with an endoscopy subscore of 3 has severeUC. In some embodiments, an anti-HJV antibody reduces an endoscopy subscore by at least 1, at least 2, or at least 3. In some embodiments, an anti-HJV antibody reduces an endoscopy subscore by 0-1, 1-2, or 2-3. In some embodiments, a subject with an endoscopic subscore of 3 has an endoscopic subscore of 2 after administration of an anti-HJV antibody. In some embodiments, a subject with an endoscopic subscore of 3 has an endoscopic subscore of 1 after administration of an anti-HJV antibody. In some embodiments, a subject with an endoscopic subscore of 3 has an endoscopic subscore of 0 after administration of an anti-HJV antibody. In some embodiments, a subject with an endoscopic subscore of 2 has an endoscopic subscore of 1 after administration of an anti-HJV antibody. In some embodiments, a subject with an endoscopic subscore of 2 has an endoscopic subscore of 0 after administration of an anti-HJV antibody. In some embodiments, a subject with an endoscopic subscore of 1 has an endoscopic subscore of 1 after administration of an anti-HJV antibody. In some embodiments, a subject with an endoscopic subscore of 1 has an endoscopic subscore of 0 after administration of an anti-HJV antibody. In some embodiments, a subject with an endoscopic subscore of 0 has an endoscopic subscore of 1 after administration of an anti-HJV antibody. In some embodiments, a subject with an endoscopic subscore of 0 has an endoscopic subscore of 0 after administration of an anti-HJV antibody.[000174] Other non-limiting examples of methods to assess UC severity include biopsy, colonoscopy, sigmoidoscopy, and stool examinations. In some embodiments, UC severity (e.g., remission) is assessed by quality of life. In some embodiments, an anti-HJV antibody is used to promote and / or maintain quality of life in a subject. In some embodiments, UC severity is assessed by disability. In some embodiments, an anti-HJV antibody is used to reduce disability of a subject. ii. Crohn ’s disease[000175] In some embodiments, the subject has Crohn’s disease (CD). Crohn's disease is a type of inflammatory bowel disease (IBD) that may affect any segment of the gastrointestinal tract. Symptoms often include abdominal pain (e.g., lower quadrant pain), diarrhea (e.g., bloody, or non-bloody diarrhea), fever, abdominal distension, weight loss, or fatigue. Complications outside of the gastrointestinal tract (e.g., extraintestinal manifestations) may include anemia, skin rashes, arthritis, inflammation of the eye, and fatigue. Presentations of Crohn disease vary considerably depending on the region of gastrointestinal involvement. Manifestations vary based on the underlying etiology of inflammation, fistula formation, orstricture formation. In some embodiments, fistula formation may result in fecaluria, pneumaturia, and / or rectovaginal fistulas. In some embodiments, a subject has an abscess associated with CD.[000176] In some embodiments, the present disclosure provides methods for reducing one or more symptoms associated with CD in a subject, the method comprising administering to the subject an effective amount of an anti-HJV antibody. In some embodiments, the administration reduces inflammation associated with CD in the subject relative to the subject prior to the administration or to a subject that did not receive the administration. In some embodiments, the administration reduces episodes of abdominal pain in the subject (e.g., episodes of abdominal pain reported by the subject) relative to the subject prior to the administration or to a subject that did not receive the administration. In some embodiments, the administration reduces episodes of abdominal pain (e.g., episodes of abdominal pain reported by the subject) by one time, twice, three times, four times, five times, six times, seven times, eight times, nine times, ten times, twenty times, thirty times or more) in a period of time (e.g., 24 hours, two day, three days, four days, five days, six days, one week, two weeks, three weeks, a month or more) relative to the subject prior to the administration or to a subject that did not receive the administration.[000177] In some embodiments, a subject having CD may experience fatigue (i.e., feeling of tiredness, exhaustion, burnout, or lack of energy that does not go away with usual amount of rest or sleep). In some embodiments, a subject having CD has physical fatigue (e.g., low energy or strength, or a feeling of heaviness). In some embodiments, a subject having CD has mental fatigue (e.g., low motivation, concentration, or alertness). In some embodiments, a subject having CD has both physical and mental fatigue. In some embodiments, a subject having active CD has fatigue associated with CD (i.e., flare up). In some embodiments, a subject who previously had surgery to treat CD is more susceptible to having fatigue (i.e., has higher chance of having fatigue relative to CD subject that did not have surgery). In some embodiments, a female CD subject is more susceptible to having fatigue relative to male CD subjects. In some embodiments, CD subjects who also has depression or anxiety is more susceptible to having fatigue relative to CD subjects who do not have depression or anxiety. In some embodiments, a CD subject with one or more extraintestinal manifestations is more susceptible to having fatigue relative to subjects who do not have extraintestinal manifestations. In some embodiments, a subject in remission phase of CD has fatigue associated with CD. In some embodiments, fatigue can be assessed by the Inflammatory Bowel Disease-Fatigue (IBD-F) patient self-assessment scale (see, e.g., Varbobitis etal., TheIBD-F Patient Self- Assessment Scale Accurately Depicts the Level of Fatigue and Predicts a Negative Effect on the Quality of Life of Patients With IBD in Clinical Remission, Inflamm Bowel Dis. 2021 May 17;27(6):826-835, the contents regarding IBD-F patient selfassessment scale is incorporated herein by reference. IBD-F patient self-assessment scale is a scoring system includes two sections of questions for a subject. Score 1 is a Fatigue Assessment Scale including five questions, which measures the severity of fatigue with a scoring scale of 0-20. If a subject scored 1 or more than 1 in score 1, the subject should proceed to answer the questions in score 2. Section 2 of Fatigue Rating Scale for IBD is IBD- Fatigue impact on Daily Activities Scale, which includes 30 questions and measures the impact of fatigue to quality of life (QoL) with a scoring scale of 0-120. In some embodiments, a score 1 value more than 7.5 indicates significant fatigue (e.g., clinically significant fatigue). In some embodiments, a subject having CD with fatigue has a score 1 based on IBD-F patient self-assessment scale in the range of 7.5 to 20, 7.5 to 19, 7.5 to 18, 7.5 to 17, 7.5 to 16, 7.5 to 15, 7.5 to 14, 7.5 to 13, 7.5 to 12, 7.5 to 11, 7.5 to 10, 7.5 to 9, 7.5 to 8, 8 to 20, 8 to 19, 8 to 18, 8 to 17, 8 to 16, 8 to 15, 8 to 14, 8 to 13, 8 to 12, 8 to 11, 8 to 10, 8 to 9, 9 to 20, 9 to 19, 9 to 18, 9 to 17, 9 to 16, 9 to 15, 9 to 14, 9 to 13, 9 to 12, 9 to 11, 9 to 10, 10 to 20, 10 to 19, 10 to 18, 10 to 17, 10 to 16, 10 to 15, 10 to 14, 10 to 13, 10 to 12, 10 to 11, 11 to 20, 11 to 19, 11 to 18, 11 to 17, 11 to 16, 11 to 15, 11 to 14, 11 to 13, 11 to 12, 12 to 20, 12 to 19, 12 to 18, 12 to 17, 12 to 16, 12 to 15, 12 to 14, 12 to 13, 13 to 20, 13 to 19, 13 to 18, 13 to 17, 13 to 16, 13 to 15, 13 to 14, 14 to 20, 14 to 19, 14 to 18, 14 to 17, 14 to 16, 14 to 15, 15 to 20, 15 to 19, 15 to 18, 15 to 17, 15 to 16, 16 to 20, 16 to 19, 16 to 18, 16 to 17, 17 to 20, 17 to 19, 17 to 18, 18 to 20, 18 to 19, or 19 to 20. In some embodiments, a subject having CD with fatigue affects the quality of life (QoL). In some embodiments, a subject having CD with fatigue as a score 2 based on IBD-F patient self-assessment scale in the range of 0-120, 5-120, 10-120, 20-120, 30-120, 40-120, 50-120, 60-120, 70-120, 80-120, 90-120, 100-120, 110-120, 0-110, 5-110, 10-110, 20-110, 30-110, 40-110, 50-110, 60-110, 70-110, 80-110, 90-110, 100-110, 0-100, 5-100, 10-100, 20-100, 30-100, 40-100, 50-100, 60-100, 70- 100, 80-100, 90-100, 0-90, 5-90, 10-90, 20-90, 30-90, 40-90, 50-90, 60-90, 70-90, 80-90, 0- 80, 5-80, 10-80, 20-80, 30-80, 40-80, 50-80, 60-80, 70-80, 0-70, 5-70, 10-70, 20-70, 30-70, 40-70, 50-70, 60-70, 0-60, 5-60, 10-60, 20-60, 30-60, 40-60, 50-60, 0-50, 5-50, 10-50, 20-50, 30-50, 40-50, 0-40, 5-40, 10-40, 20-40, 30-40, 0-30, 5-30, 10-30, 20-30, 0-20, 5-20, 10-20, 0- 10, 5-10, or 0-5. In some embodiments, the administration reduces fatigue in the subject relative to the subject prior to the administration or to a subject that did not receive the administration. In some embodiments, the administration reduces fatigue based on IBD-Fpatient self-assessment scale in the subject relative to the subject prior to the administration or to a subject that did not receive the administration. In some embodiments, the administration reduces score 1 based on IBD-F patient self-assessment scale in the subject by at least 0.5 point, by at least 1 point, by at least 2 points, by at least 2.5 points, by at least 3 points, by at least 4 points, by at least 5 points, by at least 7 points, by at least 7 points, by at least 8 points, by at least 9 points, by at least 10 points, by at least 11 points, by at least 12 points, by at least 13 points, by at least 14 points, by at least 15 points, by at least 16 points, by at least 17 points, by at least 18 points, by at least 18 points, or by at least 20 points relative to the subject prior to the administration or to a subject that did not receive the administration. In some embodiments, the administration reduces score 1 based on IBD-F patient self-assessment scale in the subject in the range of 1-2 points, 1-5 points, 1-10 points, 1-15 points, 1-20 points, 2-5 points, 2-8 points, 2-10 points, 2-12 points, 2-15 points, 2-20 points, 5-8 points, 5-10 points, 5-12 points, 5-15 points, 5-18 points, 5-20 points, 8-10 points, 8-12 points, 8-15 points, 8-18 points, 8-20 points, 10-12 points, 10-15 points, 10-18 points, 10-20 points, 12-15 points, 12-15 points, 12-18 points, 12-20 points, 15-18 points, 15-20 points, 16-18 points, 16-20 points, or 18-20 points relative to the subject prior to the administration or to a subject that did not receive the administration. In some embodiments, the administration reduces score 2 based on IBD-F patient self-assessment scale in the subject by at by at least 1 point, by at least 5 points, by at least 10 points, by at least 15 points, by at least 25 points, by at least 25 points, by at least 30 points, by at least 40 points, by at least 50 points, by at least 60 points, by at least 70 points, by at least 80 points, by at least 90 points, by at least 100 points, by at least 110 points, or by at least 120 points relative to the subject prior to the administration or to a subject that did not receive the administration. In some embodiments, the administration reduces score 2 based on IBD-F patient self-assessment scale in the subject in the range of 1-120 points, 1-110 points, 1-100 points, 1-90 points, 1-80 points, 1-70 points, 1-60 points, 1-50 points, 1-40 points, 1-30 points, 1-20 points, 1-10 points, 1-5 points, 5-120 points, 5-110 points, 5-100 points, 5-90 points, 5-80 points, 5-70 points, 5-60 points, 5-50 points, 5-40 points, 5-30 points, 5-20 points, 5-10 points, 10-120 points, 10-110 points, 10-100 points, 10-90 points, 10-80 points, 10-70 points, 10-60 points, 10-50 points, 10-40 points, 10-30 points, 10-20 points, 20-120 points, 20-110 points, 20-100 points, 20-90 points, 20-80 points, 20-70 points, 20-60 points, 20-50 points, 20-40 points, 20- 30 points, 30-120 points, 30-110 points, 30-100 points, 30-90 points, 30-80 points, 30-70 points, 30-60 points, 30-50 points, 30-40 points, 40-120 points, 40-110 points, 40-100 points, 40-90 points, 40-80 points, 40-70 points, 40-60 points, 40-50 points, 50-120 points, 50-110points, 50-100 points, 50-90 points, 50-80 points, 50-70 points, 50-60 points, 60-120 points, 60-110 points, 60-100 points, 60-90 points, 60-80 points, 60-70 points, 70-120 points, 70-110 points, 70-100 points, 70-90 points, 70-80 points, 80-120 points, 80-110 points, 80-100 points, 80-90 points, 90-120 points, 90-110 points, 90-100 points, 100-120 points, 100-110 points, or 110-120 points relative to the subject prior to the administration or to a subject that did not receive the administration.[000178] In some embodiments, fatigue can be assessed by the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue (FACIT-F) scale (see, e.g., Tinsley, A., Macklin, E. A., Korzenik, J. R., & Sands, B. E. (2011). Validation of the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) in patients with inflammatory bowel disease. Alimentary pharmacology & therapeutics, 34(11-12), 1328-1336; and facit.org / measures / facit-f) and / or the Functional Assessment of Cancer Therapy (FACT) Anemia (FACT-An) scale (see, e.g., Celia D. The Functional Assessment of Cancer Therapy- Anemia (FACT-An) Scale: a new tool for the assessment of outcomes in cancer anemia and fatigue. Seminars in Hematology. 1997 Jul;34(3 Suppl 2): 13-19; and facit.org / measures / fact- an). The FACIT-F scale contains 40 questions relating to 5 categories of well-being: physical well-being (7 questions), social well-being (7 questions), emotional well-being (6 questions), function well-being (7 questions), and fatigue (13 questions). The FACT-An scale contains the questions of the FACIT-F scale and an additional 7 questions relating to anemia. For both assessments, patients provide a score between 0-4 (inclusive) for each item. For each category, individual items are summed, multiplied by the number of items presented, and divided by the number of items answered to calculate a category score; for example, fatigue category scores for either FACIT-F or FACT-An can range from 0-52. Category scores are then summed to derive a total score, ranging from 0-160 for FACIT-F or 0-188 for FACT- An. Higher scores within these ranges indicate better quality of life (QoL). Typically, healthy individuals have a FACIT-F fatigue category score of 40 or greater (e.g., Celia D, Lai JS, Chang CH, Peterman A, Slavin M. Fatigue in cancer patients compared with fatigue in the general United States population. Cancer. 2002;94(2):528-38). In some embodiments, a score value of less than about 40 points in the fatigue category of the FACIT-F scale indicates significant fatigue (e.g., clinically significant fatigue). In some embodiments, a subject having CD with fatigue has a FACIT-F fatigue category score in the range of 0-40, 0-39, 0- 38, 0-37, 0-36, 0-35, 0-34, 0-33, 0-32, 0-31, 0-30, 0-29, 0-28, 0-27, 0-26, 0-25, 0-24, 0-23, 0- 22, 0-21, 0-20, 0-19, 0-18, 0-17, 0-16, 0-15, 0-14, 0-13, 0-12, 0-11, 0-10, 0-9, 0-8, 9-7, 0-6, or 0-5. In some embodiments, the administration reduces fatigue based on the FACIT-F scalein the subject relative to the subject prior to the administration or to a subject that did not receive the administration. In some embodiments, the administration increases a FACIT-F fatigue category score of the subject by at least 0.5 point, by at least 1 point, by at least 2 points, by at least 2.5 points, by at least 3 points, by at least 4 points, by at least 5 points, by at least 7 points, by at least 7 points, by at least 8 points, by at least 9 points, by at least 10 points, by at least 11 points, by at least 12 points, by at least 13 points, by at least 14 points, by at least 15 points, by at least 16 points, by at least 17 points, by at least 18 points, by at least 19 points, or by at least 20 points relative to the subject prior to the administration or to a subject that did not receive the administration. In some embodiments, the administration increases a FACIT-F fatigue category score in the subject in the range of 1-2 points, 1-5 points, 1-10 points, 1-15 points, 1-20 points, 2-5 points, 2-8 points, 2-10 points, 2-12 points, 2-15 points, 2-20 points, 5-8 points, 5-10 points, 5-12 points, 5-15 points, 5-18 points, 5-20 points, 8-10 points, 8-12 points, 8-15 points, 8-18 points, 8-20 points, 10-12 points, 10-15 points, 10-18 points, 10-20 points, 12-15 points, 12-15 points, 12-18 points, 12-20 points, 15- 18 points, 15-20 points, 16-18 points, 16-20 points, or 18-20 points relative to the subject prior to the administration or to a subject that did not receive the administration.[000179] In some embodiments ,the administration improves a patient’s quality of life (QoL). In some embodiments, QoL is assessed by the Patient’s Global Impression of Change (PGL C) self-assessment (see: Hurst, Hugh, and Jennifer Bolton. "Assessing the clinical significance of change scores recorded on subjective outcome measures." Journal of manipulative and physiological therapeutics 27.1 (2004): 26-35.). The PGI-C self-assessment contains a single question related to changes in condition from the beginning of a treatment, scored on a numerical scale of 1-7. Patients scoring a 6-7 on the PGI-C scale are considered to have experienced clinically significant improvements in their condition. In some embodiments, the administration improves QoL based on the PGI-C scale in the subject relative to a subject that did not receive the administration. In some embodiments, subjects having UC and receiving the administration report a PGI-C score of 5, 6, or 7.[000180] In some embodiments, QoL is assessed by the Medical Outcomes Study Short Form 36 (SF-36) (see, e.g.: Garratt AM, Schmidt L, Mackintosh A, Fitzpatrick R. Quality of life measurement: bibliographic study of patient assessed health outcome measures. Brit Med J. 2002;324: 1417-9; Contopoulos-Ioannidis DG, Karvouni A, Kouri I, loannidis JPA. SF-36 outcomes in randomized trials: a systematic review. Brit Med J. 2009;338:a3006). The SF-36 consists of 8 subscales: 1) Physical Functioning; 2) Role Limitations due to Physical Problems; 3) General Health Perceptions; 4) Vitality; 5) Social Functioning; 6) RoleLimitations due to Emotional Problems; 7) General Mental Health; and 8) Health Transition. Items within each subscale are totaled, multiplied by 10, and added to 50 to linearly transform each value to fit within a scale ranging from 0 (negative health) to 100 (positive health), wherein 50 represents the mean value; the transformed value is the corresponding score for each subscale. Certain subscale scores can be assessed together to generate a physical component summary (“PCS”) or mental component summary (“MCS”) based on factor analysis (e.g., Ware JE, Kosinski M, Bayliss MS, McHomey C, Rogers WH, Raczek A. Comparison of methods for scoring and statistical analysis of the SF-36 health profile and summary measures: summary of results from the Medical Outcomes Study. Med Care. 1995;33:AS264-79.). In some embodiments, the administration reduces fatigue in the subject relative to the subject prior to the administration or to a subject that did not receive the administration. In some embodiments, the administration reduces fatigue based on IBD-F patient self-assessment scale in the subject relative to the subject prior to the administration or to a subject that did not receive the administration. In some embodiments, the administration increases a subscale score of SF-36 in the subject by at least 1 point, by at least 2 points, by at least 3 points, by at least 4 points, by at least 5 points, by at least 6 points, by at least 7 points, by at least 8 points, by at least 9 points, by at least 10 points, by at least 11 points, by at least 12 points, by at least 13 points, by at least 14 points, by at least 15 points, by at least 16 points, by at least 17 points, by at least 18 points, by at least 19 points, by at least 20 points, by at least 21 points, by at least 22 points, by at least 23 points, by at least 24 points, by at least 25 points, by at least 26 points, by at least 27 points, by at least 28 points, by at least 29 points, or by at least 30 points relative to the subject prior to the administration or to a subject that did not receive the administration. In some embodiments, the administration increases a subscale score of SF-36 in the subject in the range of 1-2 points, 1-5 points, 1-10 points, 1-15 points, 1-20 points, 1-25 points, 1-30 points, 2-5 points, 2-8 points, 2-10 points, 2-12 points, 2-15 points, 2-20 points, 2-25 points, 2-30 points, 5-8 points, 5-10 points, 5-12 points, 5-15 points, 5-18 points, 5-20 points, 5-25 points, 5-30 points, 8-10 points, 8-12 points, 8-15 points, 8-18 points, 8-20 points, 8-25 points, 5-30 points, 10-12 points, 10-15 points, 10-18 points, 10-20 points, 10-25 points, 10-30 points, 12- 15 points, 12-15 points, 12-18 points, 12-20 points, 12-25 points, 12-30 points, 15-18 points, 15-20 points, 15-25 points, 15-30 points, 20-25 points, 20-30 points, or 25-30 points relative to the subject prior to the administration or to a subject that did not receive the administration. In some embodiments, the administration increases a PCS score of SF-36 in the subject by at least 1 point, by at least 2 points, by at least 3 points, by at least 4 points, byat least 5 points, by at least 6 points, by at least 7 points, by at least 8 points, by at least 9 points, by at least 10 points, by at least 11 points, by at least 12 points, by at least 13 points, by at least 14 points, by at least 15 points, by at least 16 points, by at least 17 points, by at least 18 points, by at least 19 points, by at least 20 points, by at least 21 points, by at least 22 points, by at least 23 points, by at least 24 points, by at least 25 points, by at least 26 points, by at least 27 points, by at least 28 points, by at least 29 points, or by at least 30 points relative to the subject prior to the administration or to a subject that did not receive the administration. In some embodiments, the administration increases a PCS score of SF-36 in the subject in the range of 1-2 points, 1-5 points, 1-10 points, 1-15 points, 1-20 points, 1-25 points, 1-30 points, 2-5 points, 2-8 points, 2-10 points, 2-12 points, 2-15 points, 2-20 points, 2-25 points, 2-30 points, 5-8 points, 5-10 points, 5-12 points, 5-15 points, 5-18 points, 5-20 points, 5-25 points, 5-30 points, 8-10 points, 8-12 points, 8-15 points, 8-18 points, 8-20 points, 8-25 points, 5-30 points, 10-12 points, 10-15 points, 10-18 points, 10-20 points, 10-25 points, 10-30 points, 12-15 points, 12-15 points, 12-18 points, 12-20 points, 12-25 points, 12- 30 points, 15-18 points, 15-20 points, 15-25 points, 15-30 points, 20-25 points, 20-30 points, or 25-30 points relative to the subject prior to the administration or to a subject that did not receive the administration. In some embodiments, the administration increases a MCS score of SF-36 in the subject by at least 1 point, by at least 2 points, by at least 3 points, by at least 4 points, by at least 5 points, by at least 6 points, by at least 7 points, by at least 8 points, by at least 9 points, by at least 10 points, by at least 11 points, by at least 12 points, by at least 13 points, by at least 14 points, by at least 15 points, by at least 16 points, by at least 17 points, by at least 18 points, by at least 19 points, by at least 20 points, by at least 21 points, by at least 22 points, by at least 23 points, by at least 24 points, by at least 25 points, by at least 26 points, by at least 27 points, by at least 28 points, by at least 29 points, or by at least 30 points relative to the subject prior to the administration or to a subject that did not receive the administration. In some embodiments, the administration increases a MCS score of SF-36 in the subject in the range of 1-2 points, 1-5 points, 1-10 points, 1-15 points, 1-20 points, 1-25 points, 1-30 points, 2-5 points, 2-8 points, 2-10 points, 2-12 points, 2-15 points, 2-20 points, 2-25 points, 2-30 points, 5-8 points, 5-10 points, 5-12 points, 5-15 points, 5-18 points, 5-20 points, 5-25 points, 5-30 points, 8-10 points, 8-12 points, 8-15 points, 8-18 points, 8-20 points, 8-25 points, 5-30 points, 10-12 points, 10-15 points, 10-18 points, 10-20 points, 10-25 points, 10-30 points, 12-15 points, 12-15 points, 12-18 points, 12-20 points, 12-25 points, 12- 30 points, 15-18 points, 15-20 points, 15-25 points, 15-30 points, 20-25 points, 20-30 points,or 25-30 points relative to the subject prior to the administration or to a subject that did not receive the administration.[000181] In some embodiments, the administration reduces diarrhea in the subject by one or more times (e.g., one time, twice, three times, four times, five times, six times, seven times, eight times, nine times, ten times, twenty times, thirty times or more) in a period of time (e.g., 24 hours, two day, three days, four days, five days, six days, one week, two weeks, three weeks, a month or more) relative to the subject prior to the administration or to a subject that did not receive the administration.[000182] In some embodiments, the administration reduces weight loss in the subject by at least 1%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100% relative to the subject prior to the administration or to a subject that did not receive the administration. In some embodiments, the administration reduces weight loss in the subject by between 1% and 100%, between 5% and 100%, between 5% and 90%, between 5% and 80%, between 5% and 70%, between 5% and 60%, between 5% and 50%, between 5% and 40%, between 5% and 30%, between 5% and 20%, between 5% and 15%, between 10% and 100%, between 10% and 90%, between 10% and 80%, between 10% and 70%, between 10% and 60%, between 10% and 50%, between 10% and 40%, between 10% and 30%, between 10% and 20%, between 10% and 15%, between 20% and 100%, between 20% and 90%, between 20% and 80%, between 20% and 70%, between 20% and 60%, between 20% and 50%, between 20% and 40%, between 20% and 30%, between 30% and 100%, between 30% and 90%, between 30% and 80%, between 30% and 70%, between 30% and 60%, between 30% and 50%, between 30% and 40%, between 40% and 100%, between 40% and 90%, between 40% and 80%, between 40% and 70%, between 40% and 60%, between 40% and 50%, between 50% and 100%, between 50% and 90%, between 50% and 80%, between 50% and 70%, between 50% and 60%, between 60% and 100%, between 60% and 90%, between 60% and 80%, between 60% and 70%, between 70% and 100%, between 70% and 90%, between 70% and 80%, between 80% and 100%, between 80% and 90%, or between 90% and 100% relative to the subject prior to the administration or to a subject that did not receive the administration.[000183] In some embodiments, Crohn’s disease can be categorized by the GI track region affected. For example, in some embodiments, CD may affect the ileum (e.g., terminal ileum) of the subject. In some embodiments, CD may affect the colon of the subject. In some embodiments, CD may affect the ileocolon of the subject. In some embodiments, CD may affect the upper GI of the subject. In some embodiments, a subject has gastroduodenalCrohn's disease which affects the stomach and the duodenum. In some embodiments, a subject has jejunoileitis which causes spotty patches of inflammation in the jejunum. In some embodiments, CD may affect part of the digestive tract, from mouth to anus, in a subject. In some embodiments, the method provided herein reduces the extent of the intestine affected by CD, the method comprising administering an effective amount of an anti-HJV antibody to the subject. In some embodiments, the administration reduces the type of intestine affected by CD (e.g., prior to treatment, the subject has CD in ileum and colon and the administration reduced the affected intestinal segment to only ileum). In some embodiments, the administration inhibits the progression (e.g., pathological progression) of CD. In some embodiments, the administration inhibits the pathological progression of CD by reducing the affected area of the intestine. In some embodiments, the administration reduces the affected area of the intestine by at least at least 1%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100% relative to the affected area prior to administration. In some embodiments, the administration reduces the affected area of the intestine by between 1% and 100%, between 5% and 100%, between 5% and 90%, between 5% and 80%, between 5% and 70%, between 5% and 60%, between 5% and 50%, between 5% and 40%, between 5% and 30%, between 5% and 20%, between 5% and 15%, between 10% and 100%, between 10% and 90%, between 10% and 80%, between 10% and 70%, between 10% and 60%, between 10% and 50%, between 10% and 40%, between 10% and 30%, between 10% and 20%, between 10% and 15%, between 20% and 100%, between 20% and 90%, between 20% and 80%, between 20% and 70%, between 20% and 60%, between 20% and 50%, between 20% and 40%, between 20% and 30%, between 30% and 100%, between 30% and 90%, between 30% and 80%, between 30% and 70%, between 30% and 60%, between 30% and 50%, between 30% and 40%, between 40% and 100%, between 40% and 90%, between 40% and 80%, between 40% and 70%, between 40% and 60%, between 40% and 50%, between 50% and 100%, between 50% and 90%, between 50% and 80%, between 50% and 70%, between 50% and 60%, between 60% and 100%, between 60% and 90%, between 60% and 80%, between 60% and 70%, between 70% and 100%, between 70% and 90%, between 70% and 80%, between 80% and 100%, between 80% and 90%, or between 90% and 100% relative to the subject prior to the administration or to a subject that did not receive the administration. Affected area of intestine by CD can be measured by any suitable methods, e.g., endoscopy, MRI, or CT scan.[000184] In some embodiments, Crohn's disease may also be categorized by the behavior of disease as it progresses, which formalized in the Vienna classification of the disease (see, Gasche et al., A simple classification of Crohn's disease: report of the Working Party for the World Congresses of Gastroenterology, Vienna 1998, Inflammatory Bowel Diseases. 6 (1): 8-15)). Unter this categorization, there are three categories of disease presentation in Crohn's disease: nonstricturing / nonpenetrating, stricturing, penetrating. Stricturing CD causes narrowing of the bowel that may lead to bowel obstruction or changes in the caliber of the feces. Penetrating CD creates abnormal passageways (fistulae) between the bowel and other structures, such as the skin. Nonstricturing / nonpenetrating CD causes inflammation without causing strictures or fistula. In some embodiments, a subject having CD is at risk of developing or has one or more fistulas.[000185] In some embodiments, a subject has fistulizing CD. In some embodiments, a subject having CD has one or more fistulas. A fistula is a chronic tract of granulation tissue between two epithelial lined surfaces. In some embodiments, chronic, transmural inflammation of the bowel wall in CD, can result in the development of sinus tracts that, once penetrating the serosa, can result in a fistula (an abnormal communication between two epithelialized surfaces). In some embodiments, a subject having CD has one or more internal fistula. An internal fistula, as used herein, refers to a fistula that arises internally. Internal fistula that forms an internal communication with another bowel layer is an enteroenteric fistula. Internal fistular that forms a communication between the intestine and other organs is an enterocutaneous or enterovesical fistula. In some embodiments, a subject has draining enterocutaneous fistula (e.g., drainage from the fistula upon gentle compression). In some embodiments, a subject has one or more enteroenteric or enterovesical fistula. In some embodiments, a subject having CD has one or more perianal fistulas. A perianal fistula is an abnormal connection between a portion of the intestine and the anorectum and / or skin on the buttock. In some embodiments, a subject having CD has one or more perianal fistula and one or more internal fistula. (McGregor et al., Pathogenesis of Fistulating Crohn’s Disease: A Review, Cellular and Molecular Gastroenterology and Hepatology, Volume 15, Issue 1, 2023, Pages 1-11). In some embodiments, the present disclosure provides methods to reduce fistula in a subject having CD, the method comprising administering the subject an effective amount of an anti-HJV antibody. In some embodiments, the administration inhibits pathologic progression of CD by reducing fistula in a subject having CD. In some embodiments, the administration fistula closure in a subject having CD. In some embodiments, the administration reduces internal fistula (e.g., draining enterocutaneousfistula) by at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, or more relative to the number of internal fistulas in the subject prior to administration or to the number of internal fistula in a subject that did not receive the administration. In some embodiments, the administration reduces internal fistula (e.g., draining enterocutaneous fistula) in the range of 1-20, 1-18, 1-15, 1-12,1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-2, 2-20, 2-18, 2-15, 2-12, 2-10, 2-9, 2-8, 2-7, 2-6, 2-5, 2-4,2-3, 3-20, 3-18, 3-15, 3-12, 3-10, 3-9, 3-8, 3-7, 3-6, 3-5, 3-4, 4-20, 4-18, 4-15, 4-12, 4-10, 4-9, 4-8, 4-7, 4-6, 4-5, 5-20, 5-18, 5-15, 5-12, 5-10, 5-9, 5-8, 5-7, 5-6, 6-20, 6-18, 6-15, 6-12, 6-10, 6-9, 6-8, 6-7, 7-20, 7-18, 7-15, 7-12, 7-10, 7-9, 7-8, 8-20, 8-18, 8-15, 8-12, 8-10, 8-9, 9- 20, 9-18, 9-15, 9-12, 9-10, 10-20, 10-18, 10-15, 10-12, 12-20, 12-18, 12-15, 15-18, 15-20, 18-20, or 20-50 relative to the number of internal fistulas in the subject prior to administration or to the number of internal fistula in a subject that did not receive the administration. In some embodiments, the administration reduces internal fistula (e.g., draining enterocutaneous fistula) by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100% relative to the number of internal fistulas in the subject prior to administration or to the number of internal fistulas in a subject that did not receive the administration. In some embodiments, the administration reduces internal fistula (e.g., draining enterocutaneous fistula) in the range of l%-100%, 5%-100%, 5%-90%, 5%-80%, 5%-70%, 5%-60%, 5%-50%, 5%-40%, 5%-30%, 5%-20%, 5%-10%, 10%-100%, 10%-90%, 10%-80%, 10%-70%, 10%-60%, 10%-50%, 10%-40%, 10%-30%, 10%-20%, 20%-100%, 20%-90%, 20%-80%, 20%-70%, 20%-60%, 20%-50%, 20%-40%, 20%-30%, 30%-100%, 30%-90%, 30%-80%, 30%-70%, 30%-60%, 30%-50%, 30%-40%, 40%-100%, 40%-90%, 40%-80%, 40%-70%, 40%-60%, 40%-50%, 50%-100%, 50%-90%, 50%-80%, 50%-70%, 50%-60%, 60%-100%, 60%-90%, 60%-80%, 60%-70%, 70%-100%, 70%-90%, 70%-80%, 80%-100%, 80%-90%, or 90%-100% relative to the number of internal fistulas in the subject prior to administration or to the number of internal fistula in a subject that did not receive the administration. In some embodiments, the administration induces fistula response in a subject. Fistula response refers to reduction of draining enterocutaneous fistula by at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or 100% in at least 2 consecutive clinic visits without increase of medication or needing surgery in a CD subject.[000186] In some embodiments, the administration reduces perianal fistula by at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, or more relative to the number of perianal fistulas in the subject priorto administration or to the number of perianal fistula in a subject that did not receive the administration. In some embodiments, the administration reduces perianal fistula relative to the number of fistula in the range of 1-20, 1-18, 1-15, 1-12, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-2, 2-20, 2-18, 2-15, 2-12, 2-10, 2-9, 2-8, 2-7, 2-6, 2-5, 2-4, 2-3, 3-20, 3-18, 3-15, 3-12, 3- 10, 3-9, 3-8, 3-7, 3-6, 3-5, 3-4, 4-20, 4-18, 4-15, 4-12, 4-10, 4-9, 4-8, 4-7, 4-6, 4-5, 5-20, 5- 18, 5-15, 5-12, 5-10, 5-9, 5-8, 5-7, 5-6, 6-20, 6-18, 6-15, 6-12, 6-10, 6-9, 6-8, 6-7, 7-20, 7-18, 7-15, 7-12, 7-10, 7-9, 7-8, 8-20, 8-18, 8-15, 8-12, 8-10, 8-9, 9-20, 9-18, 9-15, 9-12, 9-10, 10- 20, 10-18, 10-15, 10-12, 12-20, 12-18, 12-15, 15-18, 15-20, 18-20, or 20-50 relative to the number of perianal fistulas in the subject prior to administration or to the number of perianal fistula in a subject that did not receive the administration. In some embodiments, the administration reduces perianal fistula by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100% relative to the number of perianal fistulas in the subject prior to administration or to the number of perianal fistula in a subject that did not receive the administration. In some embodiments, the administration reduces perianal fistula in the range of 1%- 100%, 5%-100%, 5%-90%, 5%- 80%, 5%-70%, 5%-60%, 5%-50%, 5%-40%, 5%-30%, 5%-20%, 5%-10%, 10%-100%, 10%- 90%, 10%-80%, 10%-70%, 10%-60%, 10%-50%, 10%-40%, 10%-30%, 10%-20%, 20%- 100%, 20%-90%, 20%-80%, 20%-70%, 20%-60%, 20%-50%, 20%-40%, 20%-30%, 30%- 100%, 30%-90%, 30%-80%, 30%-70%, 30%-60%, 30%-50%, 30%-40%, 40%-100%, 40%- 90%, 40%-80%, 40%-70%, 40%-60%, 40%-50%, 50%-100%, 50%-90%, 50%-80%, 50%- 70%, 50%-60%, 60%-100%, 60%-90%, 60%-80%, 60%-70%, 70%-100%, 70%-90%, 70%- 80%, 80%-100%, 80%-90%, or 90%-100% relative to the number of perianal fistulas in the subject prior to administration or to the number of perianal fistula in a subject that did not receive the administration.[000187] In some embodiments, a subject having CD has both internal and perianal fistulas. In some embodiments, the administration reduces the total number of fistulas (e.g., combined number of internal and perianal fistulas) by at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, or more relative to the total number of fistulas (e.g., combined number of internal and perianal fistulas) in the subject prior to administration or to the total number of fistulas (e.g., combined number of internal and perianal fistulas) in a subject that did not receive the administration. In some embodiments, the administration reduces the total number of fistulas (e.g., combined number of internal and perianal fistulas) in the range of 1-20, 1-18, 1-15, 1- 12, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-2, 2-20, 2-18, 2-15, 2-12, 2-10, 2-9, 2-8, 2-7, 2-6, 2-5,2-4, 2-3, 3-20, 3-18, 3-15, 3-12, 3-10, 3-9, 3-8, 3-7, 3-6, 3-5, 3-4, 4-20, 4-18, 4-15, 4-12, 4- 10, 4-9, 4-8, 4-7, 4-6, 4-5, 5-20, 5-18, 5-15, 5-12, 5-10, 5-9, 5-8, 5-7, 5-6, 6-20, 6-18, 6-15, 6- 12, 6-10, 6-9, 6-8, 6-7, 7-20, 7-18, 7-15, 7-12, 7-10, 7-9, 7-8, 8-20, 8-18, 8-15, 8-12, 8-10, 8- 9, 9-20, 9-18, 9-15, 9-12, 9-10, 10-20, 10-18, 10-15, 10-12, 12-20, 12-18, 12-15, 15-18, 15- 20, 18-20, or 20-50 relative to the total number of fistulas (e.g., combined number of internal and perianal fistulas) in the subject prior to administration or to the total number of fistula (e.g., combined number of internal and perianal fistulas) in a subject that did not receive the administration. In some embodiments, the administration reduces the total number of fistulas (e.g., combined number of internal and perianal fistulas) by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100% relative to the total number of fistulas (e.g., combined number of internal and perianal fistulas) in the subject prior to administration or to the total number of fistula (e.g., combined number of internal and perianal fistulas) in a subject that did not receive the administration. In some embodiments, the administration reduces the total number of fistulas (e.g., combined number of internal and perianal fistulas) in the range of l%-100%, 5%-100%, 5%-90%, 5%- 80%, 5%-70%, 5%-60%, 5%-50%, 5%-40%, 5%-30%, 5%-20%, 5%-10%, 10%-100%, 10%- 90%, 10%-80%, 10%-70%, 10%-60%, 10%-50%, 10%-40%, 10%-30%, 10%-20%, 20%- 100%, 20%-90%, 20%-80%, 20%-70%, 20%-60%, 20%-50%, 20%-40%, 20%-30%, 30%- 100%, 30%-90%, 30%-80%, 30%-70%, 30%-60%, 30%-50%, 30%-40%, 40%-100%, 40%- 90%, 40%-80%, 40%-70%, 40%-60%, 40%-50%, 50%-100%, 50%-90%, 50%-80%, 50%- 70%, 50%-60%, 60%-100%, 60%-90%, 60%-80%, 60%-70%, 70%-100%, 70%-90%, 70%- 80%, 80%-100%, 80%-90%, or 90%-100% relative to the total number of fistulas (e.g., combined number of internal and perianal fistulas) in the subject prior to administration or to the total number of fistula (e.g., combined number of internal and perianal fistulas) in a subject that did not receive the administration.[000188] In some embodiments, a subject having CD is at risk of developing or has intestinal strictures. Intestinal stricture is characterized by thickening of all layers of the intestinal wall and narrowing the intestine lumen. In some embodiments, a subject having CD associated intestinal stricture develops intestinal obstruction. In some embodiments, a subject having CD associated intestinal stricture becomes resistant to CD treatment (e.g., biologic treatment). In some embodiments, the present disclosure provides methods for treating intestinal strictures associated with CD in a subject, the method comprising administering to the subject an effective amount of an anti-HJV antibody. In some embodiments, the administration reduces the thickness of intestinal wall at the site of intestinal stricture by atleast 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100% relative to the thickness of the intestinal wall at the intestinal stricture site in the subject prior to administration or to the thickness of the intestinal wall at the intestinal stricture site in a subject that did not receive the administration. In some embodiments, the administration reduces the thickness of intestinal wall at the site of intestinal stricture in the range of 1 %- 100%, 5%-100%, 5%-90%, 5%-80%, 5%-70%, 5%-60%, 5%-50%, 5%-40%, 5%-30%, 5%-20%, 5%-10%, 10%-100%, 10%-90%, 10%-80%, 10%-70%, 10%-60%, 10%-50%, 10%-40%, 10%-30%, 10%-20%, 20%-100%, 20%-90%, 20%-80%, 20%-70%, 20%-60%, 20%-50%, 20%-40%, 20%-30%, 30%-100%, 30%-90%, 30%-80%, 30%-70%, 30%-60%, 30%-50%, 30%-40%, 40%-100%, 40%-90%, 40%-80%, 40%-70%, 40%-60%, 40%-50%, 50%-100%, 50%-90%, 50%-80%, 50%-70%, 50%-60%, 60%-100%, 60%-90%, 60%-80%, 60%-70%, 70%-100%, 70%-90%, 70%-80%, 80%-100%, 80%-90%, or 90%-100% relative to the thickness of the intestinal wall at the intestinal stricture site in the subject prior to administration or to the thickness of the intestinal wall at the intestinal stricture site in a subject that did not receive the administration. In some embodiments, the administration reduces the number of intestinal strictures by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100% relative to the number of intestinal strictures in the subject prior to administration or to the number of intestinal strictures in a subject that did not receive the administration. In some embodiments, the administration reduces the number of intestinal strictures in the range of l%-100%, 5%-100%, 5%-90%, 5%-80%, 5%- 70%, 5%-60%, 5%-50%, 5%-40%, 5%-30%, 5%-20%, 5%-10%, 10%-100%, 10%-90%, 10%-80%, 10%-70%, 10%-60%, 10%-50%, 10%-40%, 10%-30%, 10%-20%, 20%-100%, 20%-90%, 20%-80%, 20%-70%, 20%-60%, 20%-50%, 20%-40%, 20%-30%, 30%-100%, 30%-90%, 30%-80%, 30%-70%, 30%-60%, 30%-50%, 30%-40%, 40%-100%, 40%-90%, 40%-80%, 40%-70%, 40%-60%, 40%-50%, 50%-100%, 50%-90%, 50%-80%, 50%-70%, 50%-60%, 60%-100%, 60%-90%, 60%-80%, 60%-70%, 70%-100%, 70%-90%, 70%-80%, 80%-100%, 80%-90%, or 90%-100% relative to the number of intestinal strictures in the subject prior to administration or to the number of intestinal strictures in a subject that did not receive the administration. In some embodiments, the administration inhibits the development and / or progression of intestinal strictures associated with CD by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100% relative to the subject prior to administration or to a subject that did not receive the administration. In some embodiments, the administration inhibits the development and / orprogression of intestinal strictures associated with CD in the range of l%-100%, 5%-100%, 5%-90%, 5%-80%, 5%-70%, 5%-60%, 5%-50%, 5%-40%, 5%-30%, 5%-20%, 5%-10%, 10%-100%, 10%-90%, 10%-80%, 10%-70%, 10%-60%, 10%-50%, 10%-40%, 10%-30%, 10%-20%, 20%-100%, 20%-90%, 20%-80%, 20%-70%, 20%-60%, 20%-50%, 20%-40%, 20%-30%, 30%-100%, 30%-90%, 30%-80%, 30%-70%, 30%-60%, 30%-50%, 30%-40%, 40%-100%, 40%-90%, 40%-80%, 40%-70%, 40%-60%, 40%-50%, 50%-100%, 50%-90%, 50%-80%, 50%-70%, 50%-60%, 60%-100%, 60%-90%, 60%-80%, 60%-70%, 70%-100%, 70%-90%, 70%-80%, 80%-100%, 80%-90%, or 90%-100% relative to the subject prior to administration or to a subject that did not receive the administration. In some embodiments, CD can be classified based on disease severity according to the Crohn’s Disease Activity Index (CD Al). CD Al is scored on a scale from 0 to 600 according to patient reported stool pattern, average abdominal pain rating over seven days, general wellbeing each day over seven days, complications (e.g., the presence of joint pains (arthralgia) or frank arthritis, inflammation of the iris or uveitis, presence of erythema nodosum, pyoderma gangrenosum, aphthous ulcers, anal fissures, fistulae or abscesses, other fistulae and / or fever during the previous week), abdominal mass, and anemia and weight change (Chen et al., Overview of Diagnosis and Medical Treatment of Inflammatory Bowel Diseases, Interventional Inflammatory Bowel Disease: Endoscopic Management and Treatment of Complications, 2018, Pages 1-15). In some embodiments, a subject that has a CD Al score of less than 150 is in remission phase of CD. In some embodiments, the subject in remission is asymptomatic. In some embodiments, the subject in remission does not have any symptomatic inflammatory sequelae.[000189] In some embodiments, a subject that has a CD Al score in the range of 150 to 220 has mild to moderate CD. In some embodiments, the subject having mild CD is ambulatory. In some embodiments, a subject having mild CD is able to tolerate oral alimentation without one or more of manifestations of dehydration, systemic toxicity, abdominal tenderness, painful mass, intestinal obstruction, or more than 10% weight loss. In some embodiments, the present disclosure provides methods for treating mild to moderate CD (e.g., treating a subject having a CD Al score in the range of 150-220, 150-210, 150-200, 150-190, 150-180, 150-170, 150-160, 160-220, 160-210, 160-200, 160-190, 160-180, 160-170, 170-220, 170-210, 170- 200, 170-190, 170-180, 180-220, 180-210, 180-200, 180-190, 190-220, 190-210, 190-200, 200-210, 200-220, or 210-220), the method comprising administering the subject an effective amount of an anti-HJV antibody. In some embodiments, the administration induces remission in a subject having mild to moderate CD and reduces the CD Al score to below 150. In someembodiments, the administration reduces the CD Al score in a subject having CD by at least 10, at least 20, at least 30, at least 40, at least 50, at least 60, at least 70, at least 80, at least 90, at least 100, at least 110, at least 120, at least 130, at least 140, at least 150, at least 160, at least 170, at least 180, at least 190, at least 200, at least 210, or at least 220 relative to the subject prior to administration or to a subject that did not receive the administration. In some embodiments, the administration reduces the CD Al score in a subject having CD by the range of 10-220, 10-210, 10-200, 10-190, 10-180, 10-170, 10-160, 10-150, 10-140, 10-130, 10-120, 10-110, 10-100, 10-90, 10-80, 10-70, 10-60, 10-50, 10-40, 10-30, 10-20, 20-220, 20-220, 20- 200, 20-190, 20-180, 20-170, 20-160, 20-150, 20-140, 20-130, 20-120, 20-110, 20-100, 20- 90, 20-80, 20-70, 20-60, 20-50, 20-40, 20-30, 30-220, 30-210, 30-200, 30-190, 30-180, 30- 170, 30-160, 30-150, 30-140, 30-130, 30-120, 30-110, 30-100, 30-90, 30-80, 30-70, 30-60, 30-50, 30-40, 40-220, 40-210, 40-200, 40-190, 40-180, 40-170, 40-160, 40-150, 40-140, 40- 130, 40-120, 40-110, 40-100, 40-90, 40-80, 40-70, 40-60, 40-50, 50-220, 50-210, 50-200, 50- 190, 50-180, 50-170, 50-160, 50-150, 50-140, 50-130, 50-120, 50-110, 50-100, 50-90, 50-80, 50-70, 50-60, 60-220, 60-210, 60-200, 60-190, 60-180, 60-170, 60-160, 60-150, 60-140, 60- 130, 60-120, 60-110, 60-100, 60-90, 60-80, 60-70, 70-220, 70-210, 70-200, 70-190, 70-180, 70-170, 70-160, 70-150, 70-140, 70-130, 70-120, 70-110, 70-100, 70-90, 70-80, 80-220, 80- 210, 80-200, 80-190, 80-180, 80-170, 80-160, 80-150, 80-140, 80-130, 80-120, 80-110, 80- 100, 80-90, 90-220, 90-210, 90-200, 90-190, 90-180, 90-170, 90-160, 90-150, 90-140, 90- 130, 90-120, 90-110, 90-100, 100-220, 100-210, 100-200, 100-190, 100-180, 100-170, 100- 160, 100-150, 100-140, 100-130, 100-120, 100-110, 110-220, 110-210, 110-200, 110-190, 110-180, 110-170, 110-160, 110-150, 110-140, 110-130, 110-120, 120-220, 120-210, 120- 200, 120-190, 120-180, 120-170, 120-160, 120-150, 120-140, 120-130, 130-220, 130-210, 130-200, 130-190, 130-180, 130-170, 130-160, 130-150, 130-140, 140-220, 140-210, 140- 200, 140-190, 140-180, 140-170, 140-160, 140-150, 150-220, 150-210, 150-200, 150-190, 150-180, 150-170, 150-160, 160-220, 160-210, 160-200, 160-190, 160-180, 160-170, 170- 220, 170-210, 170-200, 170-190, 170-180, 180-220, 180-210, 180-200, 180-190, 190-220, 190-210, 190-200, 200-210, 200-220, or 210-220 relative to the subject prior to administration or to a subject that did not receive the administration. In some embodiments, a subject has a CD Al score in the range of 220 to 450 has moderate to severe CD. In some embodiments, the subject has moderate to severe CD fails to respond to treatment for mild to moderate disease. In some embodiments, the subject that has moderate to severe CD has fever. In some embodiments, the subject that has moderate to severe CD has significant weight loss. In some embodiments, the subject that has moderate to severe CD has abdominalpain or tenderness. In some embodiments, the subject that has moderate to severe CD has intermittent nausea or vomiting. In some embodiments, the subject that has moderate to severe CD has significant anemia. In some embodiments, the present disclosure provides methods for treating moderate to severe CD (e.g., treating a subject having a CD Al score in the range of 220-450, 220-440, 220-430, 220-420, 220-410, 220-400, 220-380, 220-370, 220- 360, 220-350, 220-340, 220-330, 220-320, 220-310, 220-300, 220-290, 220-280, 220-270, 220-260, 220-250, 220-240, 220-230), the method comprising administering the subject an effective amount of an anti-HJV antibody. In some embodiments, the administration reduces the severity of CD in a subject from moderate to severe CD to mild to moderate CD (e.g., reducing the CD Al score from the range of 220-450 to the range of 150-220). In some embodiments, the administration induces remission in a subject having moderate to severe CD and reduces the CD Al score to below 150. In some embodiments, the administration reduces the CD Al score in a subject having CD by at least 10, at least 20, at least 30, at least 40, at least 50, at least 60, at least 70, at least 80, at least 90, at least 100, at least 110, at least 120, at least 130, at least 140, at least 150, at least 160, at least 170, at least 180, at least 190, at least 200, at least 210, at least 220, at least 220, at least 230, at least 240, at least 250, at least 260, at least 270, at least 280, at least 290, at least 300, at least 310, at least 320, at least 330, at least 340, at least 350, at least 360, at least 370, at least 380, at least 390, at least 400, at least 410, at least 420, at least 430, at least 440, or at least 450 relative to the subject prior to administration or to a subject that did not receive the administration. In some embodiments, the administration reduces the CD Al score in a subject having CD by the range of 10-450, 10-400, 10-350, 10-300, 10-250, 10-200, 10-150, 10-100, 10-50, 10-20, 50-450, 50-400, 50-350, 50-300, 50-250, 50-200, 50-150, 50-100, 70-450, 70-400, 70-350, 70-300, 70-250, 70-200, 70-150, 70-100, 100-450, 100-400, 100-350, 100-300, 100-250, 100-200, 100-150, 100-120, 150-450, 150-400, 150-350, 150-300, 150-250, 150-200, 150-180, 180- 450, 180-400, 180-350, 180-300, 180-250, 180-200, 200-450, 200-400, 200-350, 200-300, 200-250, 250-450, 250-400, 250-350, 250-300, 300-450, 300-400, 300-350, 350-450, 350- 400, or 400-450 relative to the subject prior to administration or to a subject that did not receive the administration.[000190] In some embodiments, a subject has a CD Al score of more than 450 has severe CD. In some embodiments, the subject having severe CD has a CD Al score in the range of 450- 1100 (e.g., 450-1100, 500-1100, 600-1100, 700-1100, 800-1100, 900-1100, 1000-1100). In some embodiments, the subject that has severe CD has persistent symptoms despite the introduction of conventional therapy (e.g., 5-ASA, corticosteroids, immunomodulators,and / or or biologies). In some embodiments, the subject that has severe CD has high fevers. In some embodiments, the subject that has severe CD has persistent vomiting. In some embodiments, the subject that has severe CD has intestinal obstruction. In some embodiments, the subject that has severe CD has peritoneal signs such as involuntary guarding or rebound tenderness, cachexia, or an abscess. (Entyvio (Vedolizumab) Common Drug Review, Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2016 Dec). In some embodiments, the administration reduces the severity of CD in a subject from severe CD to mild to moderate CD (e.g., reducing the CD Al score from the range of more than 450 to the range of 150-220). In some embodiments, the administration reduces the severity of CD in a subject from severe CD to moderate to severe CD (e.g., reducing the CD Al score from the range of more than 450 to the range of 220-450). In some embodiments, the administration induces remission in a subject having severe CD and reduces the CD Al score to below 150. In some embodiments, the administration reduces the CD Al score in a subject having CD by at least 10, at least 50, at least 70, at least 100, at least 150, at least 200, at least 250, at least 300, at least 350, at least 400, at least 450, at least 500, at least 550, at least 600, at least 650, at least 700, at least 750, at least 800, at least 850, at least 900, at least 950, at least 1000, or at least 1100 relative to the subject prior to administration or to a subject that did not receive the administration. In some embodiments, the administration reduces the CD Al score in a subject having CD by the range of 10-1100, 10-1000, 10-900, 10-800, 10-700, 10-600, 10-500, 10-400, 10-300, 10-200, 10-100, 10-50, 50-1100, 50-1000, 50-900, 50-800, 50-700, 50-600, 50-500, 50-400, 50-300, 50-200, 50-100, 100-1100, 100- 1000, 100-900, 100-800, 100-700, 100-600, 100-500, 100-400, 100-300, 100-200, 200-1100, 200-1000, 200-900, 200-800, 200-700, 200-600, 200-500, 200-400, 200-300, 300-1100, 300- 1000, 300-900, 300-800, 300-700, 300-600, 300-500, 300-400, 400-1100, 400-1000, 400- 900, 400-800, 400-700, 400-600, 400-500, 500-1100, 500-1000, 500-900, 500-800, 500-700, 500-600, 600-1100, 600-1000, 600-900, 600-800, 600-700, 700-1100, 700-1000, 700-900, 700-800, 800-1100, 800-1000, 800-900, 900-1100, 900-1000, or 1000-1100 relative to the subject prior to administration or to a subject that did not receive the administration. In some embodiments, CD can be categorized by Harvey-Bradshaw index (HBI) (Elliott etal., (1980). Simple index of Crohn's disease activity. Lancet. 1 (8173): 876). Harvey-Bradshaw index categorizes CD by only clinical parameters, including general well-being (0 = very well, 1 = slightly below average, 2 = poor, 3 = very poor, 4 = terrible), abdominal pain (0 = none, 1 = mild, 2 = moderate, 3 = severe), number of liquid stools per day, abdominal mass (0 = none, 1 = dubious, 2 = definite, 3 = tender), complications (e.g., the presence of joint pains(arthralgia) or frank arthritis, inflammation of the iris or uveitis, presence of erythema nodosum, pyoderma gangrenosum, aphthous ulcers, anal fissures, fistulae or abscesses, other fistulae and / or fever during the previous week), with one point for each. In some embodiments, a subject that has a HBI score of less than 5 is in remission phase of CD. In some embodiments, a subject that has a HBI score in the range of 5-7 has mild CD. In some embodiments, a subject that has a HBI score in the range of 8-16 has moderate CD. In some embodiments, a subject that has a HBI score more than 16 has severe CD (Baumgart et al., Inflammatory bowel disease: clinical aspects and established and evolving therapies, Lancet. 2007 May 12;369(9573): 1641-57). In some embodiments, the administration reduces CD severity from severe CD to CD of less severity (e.g., mild CD, moderate CD, or remission) based on HBI. In some embodiments, the administration reduces CD severity from moderate CD to CD of less severity (e.g., mild CD, or remission) based on HBI. In some embodiments, the administration reduces CD severity from mild CD to CD of less severity (e.g., remission) based on HBI. In some embodiments, the administration reduces the HBI score by at least 1 point, at least 2 points, at least 3 points, at least 4 points, at least 5 points, at least 6 points, at least 7 points, at least 8 points, at least 9 points, at least 10 points, at least 11 points, at least 12 points, at least 13 points, at least 14 points, at least 15 points, at least 16 points, at least 17 points, at least 18 points, at least 19 points, or at least 20 points relative to the subject prior to administration or to a subject that did not receive the administration. In some embodiments, the administration reduces the HBI score by the range of 1-20 points, 1-18 points, 1-15 points, 1-12 points, 1-10 points, 1-8 points, 1-6 points, 1-5 points, 1-3 points, 1-2 points, 5-20 points, 5-18 points, 5-15 points, 5-12 points, 5-10 points, 5-10 points, 5-15 points, 5-20 points, 2-8 points, 2-6 points, 4-7 pints, 4-10 points, 4-15 points, 3-5 points, 3-8 points, 3-12 points, 3-18 points, 10-20 points, 10-18 points, 10-15 points, 10-12 points, 15-18 points, 15- 20 points, or 18-20 points relative to the subject prior to administration or to a subject that did not receive the administration.[000191] In some embodiments, CD can be characterized and categorized by endoscopic findings. In some embodiments, endoscopic findings in CD include one or more of discontinuous distribution of longitudinal ulcers (i.e., ulcers >4 to 5 cm), cobblestone appearance, and / or small aphthous ulcerations arranged in a longitudinal fashion (Lee et al., Endoscopic Diagnosis and Differentiation of Inflammatory Bowel Disease, Clin Endosc . 2016 Jul; 49(4): 370-375. In some embodiments, the present disclosure provides methods for improving endoscopic appearance in a subject having CD, the method comprising administering the subject an effective amount of an anti-HJV antibody. In someembodiments, the administration induces mucosal healing in a subject having CD (e.g., as measured by endoscopy). In some embodiments, the administration reduces the length of the longitudinal ulcers by 1-10 cm, 2-10 cm, 5-10 cm, 8-10 cm, 1-8 cm, 3-8 cm, 5-8 cm, 7-8 cm, 1-7 cm, 2-7 cm, 4-7 cm, 6-7 cm, 6-9 cm, 6-8 cm, 6-10 cm, 7-9 cm, or 8-10 cm relative to the subject prior to administration or to a subject that did not receive the administration. In some embodiments, the administration reduces the cobblestone appearance in the subject relative to the subject prior to administration or to a subject that did not receive the administration. In some embodiments, the administration reduces the number of small aphthous ulcerations by the range of l%-100%, 5%-100%, 5%-90%, 5%-80%, 5%-70%, 5%-60%, 5%-50%, 5%- 40%, 5%-30%, 5%-20%, 5%-10%, 10%-100%, 10%-90%, 10%-80%, 10%-70%, 10%-60%, 10%-50%, 10%-40%, 10%-30%, 10%-20%, 20%-100%, 20%-90%, 20%-80%, 20%-70%, 20%-60%, 20%-50%, 20%-40%, 20%-30%, 30%-100%, 30%-90%, 30%-80%, 30%-70%, 30%-60%, 30%-50%, 30%-40%, 40%-100%, 40%-90%, 40%-80%, 40%-70%, 40%-60%, 40%-50%, 50%-100%, 50%-90%, 50%-80%, 50%-70%, 50%-60%, 60%-100%, 60%-90%, 60%-80%, 60%-70%, 70%-100%, 70%-90%, 70%-80%, 80%-100%, 80%-90%, or 90%- 100% relative to the subject prior to administration or to a subject that did not receive the administration.[000192] In some embodiments, CD can be characterized and categorized by Simplified Endoscopic Activity Score for Crohn’s Disease (SES-CD) (Daperno etal., Development and validation of a new, simplified endoscopic activity score for Crohn’s disease: the SES-CD, Gastrointestinal Endoscopy, 01 Oct 2004, 60(4):505-512). In some embodiments, SES-CD scores endoscopic findings in a CD subjects in bowel segments (e.g., ileum, right / transverse / left colon, and rectum) based on presence and size of ulcers (none = score 0; diameter 0.1-0.5 cm = score 1; 0.5-2 cm = score 2; >2 cm = score 3); extent of ulcerated surface (none = 0; <10% =1; 10%-30% =2; >30% =3); extent of affected surface (none = 0; <50% =1; 50-75% =2; >75% =3); and presence and type of narrowing (none = 0; single, can be passed = 1; multiple, can be passed = 2; cannot be passed = 3). Under SES-CD, higher SES-CD scores indicate more severe disease. In some embodiments, a subject having CD is in remission with a SES-CD score in the range of 0-2. In some embodiments, a subject has mild CD with a SES-CD score in the range of 3-6. In some embodiments, a subject has moderate CD with a SES-CD score in the range of 7-15. In some embodiments, a subject has severe CD with a SES-CD score more than 16. (Koutroumpakis et al.. Implementation of the Simple Endoscopic Activity Score in Crohn's Disease, Saudi J Gastroenterol. 2016 May- Jun; 22(3): 183-191). In some embodiments, the administration reduces CD severity fromsevere CD to CD of less severity (e.g., mild CD, moderate CD, or remission) based on SES- CD. In some embodiments, the administration reduces CD severity from moderate CD to CD of less severity (e.g., mild CD, or remission) based on SES-CD. In some embodiments, the administration reduces CD severity from mild CD to CD of less severity (e.g., remission) based on SES-CD. In some embodiments, the administration reduces the SES-CD score by at least 1 point, at least 2 points, at least 3 points, at least 4 points, at least 5 points, at least 6 points, at least 7 points, at least 8 points, at least 9 points, at least 10 points, at least 11 points, at least 12 points, at least 13 points, at least 14 points, at least 15 points, at least 16 points, at least 17 points, at least 18 points, at least 19 points, or at least 20 points relative to the subject prior to administration or to a subject that did not receive the administration. In some embodiments, the administration reduces the SES-CD score by the range of 1-20 points, 1-18 points, 1-15 points, 1-12 points, 1-10 points, 1-8 points, 1-6 points, 1-5 points, 1-3 points, 1-2 points, 5-20 points, 5-18 points, 5-15 points, 5-12 points, 5-10 points, 5-10 points, 5-15 points, 5-20 points, 2-8 points, 2-6 points, 4-7 pints, 4-10 points, 4-15 points, 3-5 points, 3-8 points, 3-12 points, 3-18 points, 10-20 points, 10-18 points, 10-15 points, 10-12 points, 15-18 points, 15-20 points, or 18-20 points relative to the subject prior to administration or to a subject that did not receive the administration.[000193] Determination of whether an amount of the antibody (e.g., anti-HJV antibody) achieves the effect (e.g., the therapeutic effect) would be evident to one of skill in the art based on the teachings provided herein. Effective amounts vary, as recognized by those skilled in the art, depending on the particular condition being treated, the severity of the condition, the individual patient parameters including age, physical condition, size, gender and weight, the duration of the treatment, the nature of concurrent therapy (if any), the specific route of administration and like factors within the knowledge and expertise of the health practitioner. The particular dosage regimen, z.e., dose, timing, and repetition, used in the method described herein will depend on the particular subject and that subject's medical history, as discussed herein.[000194] Empirical considerations, such as time to maximum effect, the half-life, and / or time above a specific concentration generally will contribute to the determination of the dosage. For example, antibodies that are compatible with the human immune system, such as humanized antibodies or fully human antibodies, may be used to prolong half-life of the antibody and to prevent the antibody being attacked by the host's immune system. Other reasons for dose-adjusting include differences in pharmacokinetics or pharmacodynamic response driven by sex, age, individual response, polymorphisms on the antibody targetand / or receptors involved in antibody clearance. Frequency of administration may be determined and adjusted over the course of therapy, and is generally, but not necessarily, based on treatment and / or suppression and / or amelioration and / or delay of a target disease / disorder. Alternatively, sustained continuous release formulations of an antibody may be appropriate. Various formulations and devices for achieving sustained release are known in the art.[000195] Dosing frequencies may vary in accordance with the claimed methods. In some embodiments, a composition may be administered once. In some embodiments, a composition will be administered on multiple occasions. In some embodiments, dosing frequency is every week, every 2 weeks, every 3 weeks, every 4 weeks, every 5 weeks, every 6 weeks, every 7 weeks, every 8 weeks, every 9 weeks, or every 10 weeks; or once every month, every 2 months, or every 3 months, or longer. In some embodiments, dosing frequency is once every 20 days, once every 21 days, once every 22 days, once every 23 days, once every 24 days, once every 25 days, once every 26 days, once every 27 days, once every 28 days, once every 29 days, once every 30 days, once every 31 days, once every 32 days, once every 33 days, once every 34 days, once every 35 days, once every 36 days, once every 37 days, once every 38 days, once every 39 days, once every 40 days, once every 41 days, once every 42 days, once every 43 days, once every 44 days, once every 45 days. In some embodiments, a composition will be administered daily, biweekly, weekly, bimonthly, monthly, or at any time interval that provide suitable (e.g., maximal) efficacy while minimizing safety risks to the subject. Generally, the efficacy and the treatment and safety risks may be monitored throughout the course of treatment.[000196] In some embodiments, a subject may be administered a composition provided herein (e.g., an anti-HJV antibody) at one or more intervals during a set period of time. In some cases, periods of time during which a subject is administered a composition at one or more intervals may be separated by periods of time in which the subject is not administered the composition. In some embodiments, the relative durations of respective periods of time may depend on the subject’s response to treatment or severity of disease or both and / or may be determined based on the judgment of a treating physician. For example, in some embodiments, an anti-HJV antibody is administered to a subject during an active phase of inflammation (e.g., during an episode of IBD), but not during an inactive phase of inflammation (e.g., not when IBD is in remission).[000197] Generally, for administration of any of the antibodies described herein, a dose may be about 50 mg, 75 mg, or 100 mg. However, in some embodiments, the dose of the anti-HJV antibody can be in a range of 5 mg to 250 mg. In some embodiments, the dose of the anti-HJV antibody is between 5-250 mg, between 5-240g / kg, between 5-230 mg, between 5- 220 mg, between 5-210 mg, between 5-200 mg, between 5-190 mg, between 5-180 mg, between 5-170 mg, between 5-160 mg, between 5-150 mg, between 5-140 mg, between 5- 130 mg, between 5-120 mg, between 5-110 mg, between 5-100 mg, between 5-90 mg, between 5-80 mg, between 5-70 mg, between 5-60 mg, between 5-50 mg, between 5-40 mg, between 5-30 mg, between 5-20 mg, between 5-10 mg, between 10-250 mg, between 10- 240g / kg, between 10-230 mg, between 10-220 mg, between 10-210 mg, between 10-200 mg, between 10-190 mg, between 10-180 mg, between 10-170 mg, between 10-160 mg, between 10-150 mg, between 10-140 mg, between 10-130 mg, between 10-120 mg, between 10-110 mg, between 10-100 mg, between 10-90 mg, between 10-80 mg, between 10-70 mg, between 10-60 mg, between 10-50 mg, between 10-40 mg, between 10-30 mg, between 10-20 mg, between 20-250 mg, between 20-240g / kg, between 20-230 mg, between 20-220 mg, between 20-210 mg, between 20-200 mg, between 20-190 mg, between 20-180 mg, between 20-170 mg, between 20-160 mg, between 20-150 mg, between 20-140 mg, between 20-130 mg, between 20-120 mg, between 20-110 mg, between 20-100 mg, between 20-90 mg, between 20-80 mg, between 20-70 mg, between 20-60 mg, between 20-50 mg, between 20-40 mg, between 20-30 mg, between 30-250 mg, between 30-240g / kg, between 30-230 mg, between 30-220 mg, between 30-210 mg, between 30-200 mg, between 30-190 mg, between 30-180 mg, between 30-170 mg, between 30-160 mg, between 30-150 mg, between 30-140 mg, between 30-130 mg, between 30-120 mg, between 30-110 mg, between 30-100 mg, between 30-90 mg, between 30-80 mg, between 30-70 mg, between 30-60 mg, between 30-50 mg, between 30-40 mg, between 40-250 mg, between 40-240g / kg, between 40-230 mg, between 40-220 mg, between 40-210 mg, between 40-200 mg, between 40-190 mg, between 40-180 mg, between 40-170 mg, between 40-160 mg, between 40-150 mg, between 40-140 mg, between 40-130 mg, between 40-120 mg, between 40-110 mg, between 40-100 mg, between 40-90 mg, between 40-80 mg, between 40-70 mg, between 40-60 mg, between 40-50 mg, between 50-250 mg, between 50-240g / kg, between 50-230 mg, between 50-220 mg, between 50-210 mg, between 50-200 mg, between 50-190 mg, between 50-180 mg, between 50-170 mg, between 50-160 mg, between 50-150 mg, between 50-140 mg, between 50-130 mg, between 50-120 mg, between 50-110 mg, between 50-100 mg, between 50-90 mg, between 50-80 mg, between 50-70 mg, between 50-60 mg, between 60-250 mg, between 60-240g / kg, between 60-230 mg, between 60-220 mg, between 60-210 mg, between 60-200 mg, between 60-190 mg, between 60-180 mg, between 60-170 mg, between 60-160 mg, between 60-150mg, between 60-140 mg, between 60-130 mg, between 60-120 mg, between 60-110 mg, between 60-100 mg, between 60-90 mg, between 60-80 mg, between 60-70 mg, between 70- 250 mg, between 70-240g / kg, between 70-230 mg, between 70-220 mg, between 70-210 mg, between 70-200 mg, between 70-190 mg, between 70-180 mg, between 70-170 mg, between 70-160 mg, between 70-150 mg, between 70-140 mg, between 70-130 mg, between 70-120 mg, between 70-110 mg, between 70-100 mg, between 70-90 mg, between 70-80 mg, between 80-250 mg, between 80-240g / kg, between 80-230 mg, between 80-220 mg, between 80-210 mg, between 80-200 mg, between 80-190 mg, between 80-180 mg, between 80-170 mg, between 80-160 mg, between 80-150 mg, between 80-140 mg, between 80-130 mg, between 80-120 mg, between 80-110 mg, between 80-100 mg, between 80-90 mg, between 90-250 mg, between 90-240g / kg, between 90-230 mg, between 90-220 mg, between 90-210 mg, between 90-200 mg, between 90-190 mg, between 90-180 mg, between 90-170 mg, between 90-160 mg, between 90-150 mg, between 90-140 mg, between 90-130 mg, between 90-120 mg, between 90-110 mg, between 90-100 mg, between 100-250 mg, between 100- 240g / kg, between 100-230 mg, between 100-220 mg, between 100-210 mg, between 100-200 mg, between 100-190 mg, between 100-180 mg, between 100-170 mg, between 100-160 mg, between 100-150 mg, between 100-140 mg, between 100-130 mg, between 100-120 mg, between 100-110 mg, between 110-250 mg, between 110-240g / kg, between 110-230 mg, between 110-220 mg, between 110-210 mg, between 110-200 mg, between 110-190 mg, between 110-180 mg, between 110-170 mg, between 110-160 mg, between 110-150 mg, between 110-140 mg, between 110-130 mg, between 110-120 mg, between 120-250 mg, between 120-240g / kg, between 120-230 mg, between 120-220 mg, between 120-210 mg, between 120-200 mg, between 120-190 mg, between 120-180 mg, between 120-170 mg, between 120-160 mg, between 120-150 mg, between 120-140 mg, between 120-130 mg, between 130-250 mg, between 130-240g / kg, between 130-230 mg, between 130-220 mg, between 130-210 mg, between 130-200 mg, between 130-190 mg, between 130-180 mg, between 130-170 mg, between 130-160 mg, between 130-150 mg, between 130-140 mg, between 140-250 mg, between 140-240g / kg, between 140-230 mg, between 140-220 mg, between 140-210 mg, between 140-200 mg, between 140-190 mg, between 140-180 mg, between 140-170 mg, between 140-160 mg, between 140-150 mg, between 150-250 mg, between 150-240g / kg, between 150-230 mg, between 150-220 mg, between 150-210 mg, between 150-200 mg, between 150-190 mg, between 150-180 mg, between 150-170 mg, between 150-160 mg, between 160-250 mg, between 160-240g / kg, between 160-230 mg, between 160-220 mg, b...

Claims

CLAIMSWhat is claimed is:

1. A method for inhibiting inflammation in a subject, the method comprising administering an effective amount of an anti-hemojuvelin (HJV) antibody to the subject having inflammation associated with barrier dysfunction.

2. The method of claim 1, wherein the barrier dysfunction is intestinal barrier dysfunction.

3. The method of claim 2, wherein the subject has increased intestinal permeability relative to a subject that does not have intestinal barrier dysfunction.

4. The method of claim 2 or 3, wherein the subject has intestinal mucosal barrier dysfunction.

5. The method of any one of claim 2-4, wherein the subject has an aberrant immune response to a gastrointestinal (GI) tract microbiome.

6. The method of any one of claims 1-5, wherein the administration reduces systemic inflammation in the subject.

7. The method of claim 6, wherein the administration reduces the number of circulating white blood cells.

8. The method of claim 6 or 7, wherein the administration reduces the number of circulating neutrophils.

9. The method of any one of claims 1-8, wherein the administration reduces local inflammation at a site of the barrier dysfunction.

10. The method of claim 9, wherein the administration reduces immune cell infiltration at the site of the barrier dysfunction.

11. The method of claim 9 or 10, wherein the administration reduces neutrophil infiltration at the site of the barrier dysfunction.

12. The method of any one of claims 1-11, wherein the administration improves intestinal barrier function.

13. The method of any one of claims 1-12, wherein the subject has ulcerative colitis.

14. The method of any one of claims 1-12, wherein the subject has Crohn’s disease.

15. A method of treating a subject, the method comprising administering an effective amount of an anti-hemojuvelin (HJV) antibody to a subject having inflammation associated with inflammatory bowel disease (IBD).

16. A method for treating inflammatory bowel disease (IBD) in a subject, the method comprising administering an effective amount of an anti-hemojuvelin (HJV) antibody to the subject, wherein the subject has inflammation associated with IBD.

17. A method for treating a subject having active inflammatory bowel disease (IBD), the method comprising administering an effective amount of an anti-hemojuvelin (HJV) antibody to the subj ect.

18. A method for treating a subject having chronic inflammatory bowel disease (IBD), the method comprising administering an effective amount of an anti-hemojuvelin (HJV) antibody to the subj ect.

19. A method for treating inflammation in a subject having inflammatory bowel disease (IBD), the method comprising administering an effective amount of an anti-hemojuvelin (HJV) antibody to the subject.

20. The method of any one of claims 15-19, wherein the subject has intestinal mucosal inflammation associated with IBD.

21. The method of any one of claims 15-20, wherein the subject has an aberrant immune response to a gastrointestinal (GI) tract microbiome.

22. The method of any one of claims 15-21, wherein the subject has acute phase IBD.

23. The method of any one of claims 15-21, wherein the subject has chronic phase IBD.

24. The method of any one of claims 15-23, wherein the administration reduces systemic inflammation in the subject.

25. The method of claim 24, wherein the administration reduces the number of circulating white blood cells.

26. The method of claim 24 or 25, wherein the administration reduces the number of circulating neutrophils.

27. The method of any one of claims 15-26, wherein the administration reduces intestinal mucosal inflammation at a site of the barrier dysfunction.

28. The method of claim 27, wherein the administration reduces immune cell infiltration in the intestine.

29. The method of claim 27 or 28, wherein the administration reduces neutrophil infiltration in the intestine.

30. The method of any one of claims 15-29, wherein the administration inhibits the development of intestinal stricture.

31. The method of any one of claims 1-30, wherein the subject is not responsive to or cannot tolerate treatment with one or more of aminosalicylates (5-ASAs), corticosteroids, sphingosine 1 -phosphate receptor modulators, immunomodulators, Janus kinase (JAK) inhibitors, tumor necrosis factor (TNF) inhibitors, integrin antagonists, interleukin (IL)-23 antagonists, or IL- 12 antagonists.

32. The method of any one of claims 15-31, wherein the subject has ulcerative colitis.

33. The method of claim 32, wherein the subject has mild to moderate active ulcerative colitis.

34. The method of claim 32, wherein the subject has moderate to severe active ulcerative colitis.

35. The method of claim 32, wherein the subject has severe active ulcerative colitis.

36. The method of any one of claims 32-35, wherein the subject has a Mayo score in the range of 3-12 prior to the administration.

37. The method of any one of claims claim 32-36, wherein the administration decreases the Mayo score by at least 3 points.

38. The method of any one of claims 32-37, wherein the subject has a Mayo endoscopic subscore (MES) of 1-3 prior to the administration.

39. The method of any one of claims 32-38, wherein the administration improves endoscopic appearance in the subject.

40. The method of claim 39, wherein the administration decreases MES by at least 1 point.

41. The method of any one of claim 32-40, wherein the administration induces endoscopic remission in the subject.

42. The method of any one of any one of claims 32-40, wherein the administration maintains endoscopic remission in the subject.

43. The method of any one of claims 32-42, wherein the administration reduces stool frequency or bowel movements.

44. The method of any one of claims 32-43, wherein the administration reduces rectal bleeding.

45. The method of any one of claims 32-44, wherein the administration induces clinical remission in the subject.

46. The method of any one of claims 32-45, wherein the administration maintains clinical remission in the subject.

47. The method of any one of claims 32-46, wherein the administration reduces the need for hospitalization due to severe uncreative colitis.

48. The method of any one of claims 32-47, wherein the administration reduces extraintestinal symptoms of ulcerative colitis in the subject.

49. The method of claim 48, wherein the administration reduces fatigue.

50. The method of any one of claims 15-31, wherein the subject has Crohn’s disease (CD).

51. The method of claim 50, wherein the subject has a Crohn’s Disease Activity Index (CD Al) of at least 150 prior to the administration.

52. The method of claim 50, wherein the subject has a CD Al in the range of 150-450.

53. The method of claim 50, wherein the subject has a CD Al more than 450.

54. The method of any one of claims 52-53, wherein the administration reduces CD Al by at least 70.

55. The method of any one of claims 50-54, wherein the subject has one or more fistulas.

56. The method of claim 55, wherein the administration reduces the number of fistulas in the subject relative to the number of fistulas in the subject prior to the administration.

57. The method of claim 55 or 56, wherein the administration maintains fistular closure in the subject.

58. The method of any one of claims 50-57, wherein the administration reduces the number of draining enterocutaneous fistulas in the subject.

59. The method of any one of claims 50-58, wherein the administration improves endoscopic appearance.

60. The method of any one of claims 50-59, wherein the administration promotes mucosal healing.

61. The method of any one of claims 50-60, wherein the administration reduces hospitalization of the subject.

62. The method of any one of claims 50-61, wherein the administration reduces a need for corticosteroids in the subject.

63. The method of any one of claims 50-62, wherein the administration induces clinical remission in the subject.

64. The method of any one of claims 50-63, wherein the administration maintains clinical remission in the subject.

65. The method of any one of claims 50-64, wherein the administration reduces fatigue in the subject.

66. A method of treating ulcerative colitis (UC), the method comprising administering an effective amount of an anti-hemojuvelin (HJV) antibody to a subject having UC and experiencing mucosal inflammation.

67. The method of claim 66, wherein the subject has acute phase UC.

68. The method of claim 66, wherein the subject has chronic phase UC.

69. The method of any one of claim 66-68, wherein the administration promotes mucosal healing in the subject.

70. The method of any one of claims 66-69, wherein the administration reduces shortening of colon in the subject.

71. The method of any one of claims 66-70, wherein the administration reduces weight loss in the subject.

72. The method of any one of claims 66-71, wherein the administration reduces stool frequency in the subject.

73. The method of any one of claims 66-72, wherein the administration reduces rectal bleeding in the subject.

74. The method of any one of claims 66-73, wherein the administration reduces systemic inflammation in the subject.

75. The method of claim 74, wherein the administration reduces the number of circulating white blood cell in the subject76. The method of claim 74 or 75, wherein the administration reduces the number of circulating neutrophils in the subject.

77. The method of any one of claims 66-76, wherein the administration increases circulating red blood cell levels in the subject.

78. The method of any one of claims 66-77, wherein the administration increases hemoglobin in the subject.

79. The method of any one of claims 66-78, wherein the administration increases mean corpuscular hemoglobin (MCH) in the subject.

80. The method of any one of claims 66-79, wherein the administration increases transferrin saturation (TSAT%) in the subject.

81. The method of any one of claims 66-80, wherein the administration increases serum iron in the subject.

82. The method of any one of claims 1-81, wherein the anti-HJV antibody is administered in combination with one or more of aminosalicylates (5-ASA), corticosteroids, sphingosine1 -phosphate receptor modulators, immunomodulators, Janus kinase (JAK) inhibitors, tumor necrosis factor (TNF) inhibitors, integrin antagonists, interleukin (IL)-23 antagonists, or IL- 12 antagonists.

83. The method of any one of claims 1-82, wherein the anti-HJV antibody is administered intravenously or subcutaneously.

84. The method of any one of claims 1-83, wherein the antibody comprises a heavy chain (HC) complementarity determining region (CDR) 1 (HC CDR1) comprising the amino acid of SEQ ID NO: 1, a HC CDR2 comprising the amino acid of SEQ ID NO: 2, a HC CDR3 comprising the amino acid of SEQ ID NO: 3; a light chain (LC) CDR1 comprising the amino acid of SEQ ID NO: 17, a LC CDR2 comprising the amino acid of SEQ ID NO: 5, and a LC CDR3 comprising the amino acid of SEQ ID NO: 27.

85. The method of any one of claims 1-84, wherein the anti-HJV antibody comprises a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 38, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 39.

86. The method of any one of claims 1-85, wherein the anti-HJV antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 61, and a light chain comprising the amino acid sequence of SEQ ID NO: 62.

87. The method of any one of claims 1-85, wherein the anti-HJV antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 63, and a light chain comprising the amino acid sequence of SEQ ID NO: 62.

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