TL1A patient selection methods, systems, and devices

Abstract

Provided are methods, systems, and kits for selecting a patient for treatment with a therapeutic agent based on a presence of a genotype associated with a positive therapeutic response to the therapeutic agent. The therapeutic agent, in some embodiments, is an inhibitor of TL1A activity or expression, such as for example, an anti-TL1A antibody.

Description

TL1A PATIENT SELECTION METHODS, SYSTEMS, AND DEVICES CROSS-REFERENCE

[0001] This application claims the benefit of U.S. Patent Application No. 62 / 847,798, filed May 14, 2019, which is hereby incorporated by reference in its entirety. SEQUENCE LISTING

[0002] The instant application contains a Sequence Listing which has been submitted electronically in ASCII format and is hereby incorporated by reference in its entirety. Said ASCII copy, created on May 6, 2020, is named 56884-761_601_SL.txt and is 14,467,905 bytes in size. BACKGROUND

[0003] Inflammatory disease, fibrostenotic disease, and fibrotic disease pose a significant health burden worldwide due to the vast number of individuals affected and heterogeneous disease pathogenesis and varied clinical manifestations. One such disease is inflammatory bowel disease (IBD), which has two common forms, Crohn’s disease (CD) and ulcerative colitis (UC). IBD is the chronic, relapsing inflammatory disorders of the gastrointestinal tract. Incidences of IBD are prevalent, affecting nearly three million individuals in the United States alone.

[0004] Few treatment options are available to patients that suffer from inflammatory disease, fibrostenotic disease, and fibrotic disease. Existing anti-inflammatory therapy such as steroids and tumor necrosis factor (TNF) inhibitors are typically used as a first line treatment for treating IBD. Unfortunately, a significant number of patients experience a lack of response or a loss of response to existing anti-inflammatory therapies, especially TNF inhibitors. While the patient is treated with an anti-inflammatory therapy that is ineffective, the disease worsens. Surgery, in the form of structureplasty (reshaping of the intestine) or resection (removal of the intestine), is the only treatment option for patients that do not respond to first line therapies. Surgical treatments for IBD are invasive, causing post-operative risks for an estimated third of patients undergoing surgery, such as anastomotic leak, infection, and bleeding.

[0005] The pathogenesis of inflammatory disease, fibrostenotic disease, and fibrotic disease, like IBD, is thought to involve an uncontrolled immune response that may be triggered by certain environmental factors in a genetically susceptible individual. The heterogeneity of disease pathogenesis and clinical course, combined with the variable response to treatment and its associated side effects, suggests a personalized medicine approach to treating these diseases is the best treatment strategy. Yet there are very few personalized therapies available to patients. Accordingly, there is a need to identify targeted therapeutic approaches for the treatment of inflammatory disease, fibrostenotic disease, and fibrotic disease and subclinical phenotypes thereof, and an even greater need to develop reliable methodology to identifying patients who, based on their genotype, may respond to any given therapeutic approach. The needed methodologies would also identify subjects not yet diagnosed who are at risk of developing the disease, for which preventative interventions could be prescribed to reduce the growing health burden.

[0006] Genome Wide Association Studies (GW AS) have provided researchers the ability to identify genetic variants (e.g., polymorphisms) that are significantly associated with IBD and subclinical phenotypes of IBD. GWAS compare the allele frequency in a given population of a particular genetic variant between unrelated cases and controls, each case representing an affected individual (e.g., patient with IBD) and each control representing an individual without IBD. GWAS, the Immunochip, and their meta-analysis have enabled the discovery of over 200 polymorphisms associated with IBD, including CD and UC.

[0007] The first GWAS on IBD identified ZNFSF / 5 as an IBD locus containing several polymorphisms associated with IBD. TNFSF15 protein, also known as TL1A, isa proinflammatory molecule which stimulates proliferation and effector functions of CD8 (+) cytotoxic T cells as well as Th, Th2, and Th17 cells in the presence of TCR stimulation. TL1A is believed to be involved in the pathogenesis of IBD by bridging the innate and adaptive immune response, modulating adaptive immunity by augmenting Th1, Th2, and Th17 effector cell function, and T-cell accumulation and immunopathology of inflamed tissue. Studies have demonstrated that patients with IBD who carry certain risk alleles at the 7NFSF / 5 locus show an increase in TNFSF15 (TL1A) expression and are more likely to develop severe forms of IBD, as compared to individuals who do not carry the risk alleles. These findings suggest that inhibiting TL1A expression and / or activity may be a promising therapeutic strategy in a variety of T cell- dependent autoimmune diseases, including IBD. These findings also suggest that certain TNFSF15 genotypes in patients that confer a risk of increased TL1A expression and / or severe forms of disease may prove useful in the prognosis, diagnosis and treatment of these individuals.

[0008] Identifying potential therapeutic targets for the treatment of disease and methods of selecting patients for treatment on the basis of GWAS alone suffer from significant drawbacks. For example, GWAS relies on linear polymorphism-polymorphism associations between known risk loci and phenotypic traits, which fail to capture high-dimensional non-linear polymorphism interactions, such as the types of relationships reflective of unknown biology. In addition, individual polymorphisms identified using GWAS often have small effect sizes in a given population. Thus, polymorphisms identified by GWAS are of limited use in predicting a susceptibility to complex diseases, such as IBD (e.g., CD, UC). Further, GWAS fail to convey or account for the biological mechanisms underlying the genetic associations between a genetic variant and a phenotypic outcome (e.g., IBD), rendering them of limited use in identifying therapeutic targets. SUMMARY

[0009] Provided herein are genotypes associated with, and therefore predictive of, a positive therapeutic response of a subject or patient to an inhibitor of TL1A activity or expression (e.g., anti-TL1A antibody) that have been identified using a machine-learning based approach. The machine-learning based approach described herein enables the identification of combinations of polymorphisms with linear and non-linear interactions that more accurately predict phenotypes of complex disease, such as IBD, as compared to traditional GWAS alone. The genotypes described herein are associated with an increase in a level of ZNFSF / 5 (TL1A) protein expression in a sample obtained from a subject or patient, as compared to a reference level of TNFSF15 (TL1A) protein expression (e.g., derived from a normal individual). The genotypes disclosed herein are located at gene or genetic loci that are involved either directly or indirectly with TL1A-mediated or T-cell dependent inflammatory pathways. In addition, some of the genotypes provided herein are also significantly associated with inflammatory bowel disease (IBD), such as Crohn’s disease (CD). The genotypes are useful for selecting a patient or a subject for treatment with an inhibitor of TL1A activity or expression. The patient may be diagnosed with IBD, CD, or both. The subject may be suspected of having IBD, CD, or both.

[0010] Non-limiting practical applications of the associations between the genotypes described herein and incidences of clinical and subclinical phenotypes in certain populations of individuals are provided herein. For example, some genotypes of the present disclosure can be used to predict a risk that a subject will develop a TL1A-mediated inflammatory disease, fibrostenotic disease, or a fibrotic disease. The genotypes are also useful to predict whether a patient diagnosed with some form of an inflammatory, fibrotic or fibrostenotic disease will develop a severe form of the disease, such as a subclinical phenotype thereof.

[0011] Further practical applications of the associations between the genotypes described herein include, without limitation, methods, systems, and kits for selecting a patient diagnosed with IBD or a subject suspected of having IBD for treatment with an inhibitor of TL1A activity or expression, provided the patient or the subject is a carrier of the genotype described herein. In addition, or alternatively, practical applications of the associations between the genotypes disclosed herein and a variation in an expression of ZNFSF15 (TL1A) are provided herein. In some cases, the genotypes can be used to identify a patient who may be suitable for treatment with a targeted TL1A therapy (e.g., a patient carrying a genotype associated with an increase in TL1A may be suitable for a treatment with an anti-TL1A therapy). An exemplary condition includes Crohn’s disease (CD). An exemplary inhibitor of TL1A activity or expression is an anti- TL1A antibody. In some instances, the anti-TL1A antibody is a neutralizing anti-TL1A antibody.

[0012] Aspects disclosed herein provide methods of treating an inflammatory, a fibrotic, or a fibrostenotic disease or condition in a subject, the method comprising administering to the subject a therapeutically effective amount of an inhibitor of Tumor necrosis factor-like cytokine 1A (TL1A) activity or expression, provided a presence of at least three polymorphisms is detected in a sample obtained from the subject, wherein the at least three polymorphisms are predictive that the subject will therapeutically respond to the inhibitor of TL1A at a positive predictive value of at least about 70%. In some embodiments, the at least three polymorphisms comprises rs1892231, rs56124762, rs6478109, 12070558, rs2070561, rs11897732, rs6740739, 1517796285, rs7935393, 1512934476, 1512457255, 152070557, 154246905, 1510974900, 1512434976, rs16901748, rs2815844, rs889702, rs2409750, rs1541020, rs4942248, rs12934476, 1512457255, rs2297437, rs41309367, rs10733509, 1510750376, rs10932456, rs1326860, 151528663, 15951279, rs9806914, 157935393, rs1690492, 15420726, rs7759385, rs10974900, 151326860, 152548147, 152815844, 15889702, rs9806914, rs7278257, or rs11221332, or a proxy polymorphism in linkage disequilibrium therewith as determined with an R? of at least 0.85, or a combination thereof

[0013] In some embodiments, the at least three polymorphisms comprise: rs6478109, 1556124762, and rs1892231; rs6478109, rs56124762, and rs16901748; rs6478109, rs1892231, and rs16901748; rs56124762, rs1892231, and rs16901748; rs6478109, rs2070558, and 151892231; rs6478109, rs2070558, and rs16901748, rs6478109, rs1892231, and rs16901748; 152070558, 151892231, and rs16901748; rs6478109, rs2070561, and rs1892231; rs6478109, 1$2070561 , and rs16901748; rs6478109, rs1892231, and rs16901748; rs2070561, rs1892231, and rs16901748; rs6478109, rs7935393, and rs1892231; rs6478109, 1s7935393, and rs9806914; 156478109, rs7935393, and rs7278257; rs6478109, rs7935393, and rs2070557; rs6478109, 181892231, and rs9806914; rs6478109, rs1892231, and rs7278257; rs6478109, rs1892231, and 152070557; rs6478109, rs9806914, and rs7278257; rs6478109, rs9806914, and rs2070557; 156478109, rs7278257, and rs2070557; rs7935393, rs1892231, and rs9806914; rs7935393, 1$1892231, and rs7278257, 1s7935393, rs1892231, and rs2070557; rs7935393, rs9806914, and 187278257; 187935393, rs9806914, and rs2070557; rs7935393, 137278257, and rs2070557, 151892231, rs9806914, and rs7278257; rs1892231, rs9806914, and rs2070557; rs1892231, 187278257, and 152070557, or rs9806914, 1s7278257, and rs2070557. In some embodiments, the at least three polymorphisms further comprises a fourth polymorphism comprising rs16901748, 1s1892231, rs56124762, rs6478109, 1s2070558, rs2070561, 1511897732, rs6740739, 1s17796285, 157935393, rs12934476, 1512457255, rs2070557, rs4246905, rs10974900, rs12434976, 152815844, rs889702, rs2409750, 151541020, rs4942248, 1512934476, rs12457255, 152297437, 1541309367, rs10733509, rs10750376, rs10932456, rs1326860, rs1528663, rs951279, rs9806914, 157935393, 151690492, 15420726, 157759385, rs10974900, rs1326860, rs2548147, 1s2815844, 15889702, rs9806914, rs7278257, or rs11221332, or a proxy polymorphism in linkage disequilibrium therewith as determined with an R? of at least 0.85, or a combination thereof. In some embodiments, the at least three polymorphisms comprise rs6478109, rs56124762, and 1s1892231. In some embodiments, the at least three polymorphisms comprise rs6478109, 1$56124762, and rs16901748. In some embodiments, the at least three polymorphisms comprise 1$6478109, 151892231, and rs16901748. In some embodiments, the at least three polymorphisms comprise 1s56124762, rs1892231, and rs16901748. In some embodiments, the proxy polymorphism in linkage disequilibrium is independently associated with a clinical phenotype associated with the inflammatory, the fibrotic, or the fibrostenotic disease or condition in the subject. In some embodiments, the clinical phenotype is stricturing and penetrating disease.

[0014] In some embodiments, the presence of the at least three polymorphisms is predictive that the subject will therapeutically respond to the inhibitor of TL1A at a positive predictive value of at least about 75%. In some embodiments, the presence of the at least three polymorphisms is predictive that the subject will therapeutically respond to the inhibitor of TL1A at a positive predictive value of at least about 80%. In some embodiments, the presence of the at least three polymorphisms is predictive that the subject will therapeutically respond to the inhibitor of TL1A at a positive predictive value of at least about 85%. In some embodiments, the presence of the at least three polymorphisms is predictive that the subject will therapeutically respond to the inhibitor of TL1A at a positive predictive value of at least about 90%. In some embodiments, the presence of the at least three polymorphisms is predictive that the subject will therapeutically respond to the inhibitor of TL1A at a positive predictive value of at least about 95%. In some embodiments, the presence of the at least three polymorphisms is predictive that the subject will therapeutically respond to the inhibitor of TL1A with a specificity of at least about 70%. In some embodiments, the presence of the at least three polymorphisms is predictive that the subject will therapeutically respond to the inhibitor of TL1A with a specificity of at least about 75%. In some embodiments, the presence of the at least three polymorphisms is predictive that the subject will therapeutically respond to the inhibitor of TL1A with a specificity of at least about 80%. In some embodiments, the presence of the at least three polymorphisms is predictive that the subject will therapeutically respond to the inhibitor of TL1A with a specificity of at least about 85%. In some embodiments, the presence of the at least three polymorphisms is predictive that the subject will therapeutically respond to the inhibitor of TL1A with a specificity of at least about 90%. In some embodiments, the presence of the at least three polymorphisms is predictive that the subject will therapeutically respond to the inhibitor of TL1A with a specificity of at least about 95%.

[0015] In some embodiments, the at least three polymorphisms are detected in the sample by subjecting the sample to an assay configured to detect a presence of at least three nucleotides corresponding to nucleic acid position 501 within SEQ ID NOS: 1-41, or 57-59. In some embodiments, the assay comprises polymerase chain reaction (PCR), quantitative reverse- transcription PCR (qPCR), automated sequencing, or genotype array.

[0016] In some embodiments, the inflammatory, fibrotic, or fibrostenotic disease or condition comprises inflammatory bowel disease, Crohn’s disease, obstructive Crohn’s disease, ulcerative colitis, intestinal fibrosis, intestinal fibrostenosis, rheumatoid arthritis, or primary sclerosing cholangitis. In some embodiments, the Crohn’s disease is ileal, ileocolonic, or colonic Crohn’s disease. In some embodiments, the subject has, or is at risk for developing, a non-response or loss-of-response to a standard therapy comprising glucocorticosteriods, anti-TNF therapy, anti- a4-b7 therapy, anti-IL12p40 therapy, or a combination thereof. In some embodiments, the inhibitor of TL1A is an anti-TL1A antibody or antigen-binding fragment. In some embodiments, the anti-TL1A antibody binds to the same region of human TL1A as a reference antibody selected from Table 2B. In some embodiments, methods further comprise administering an additional therapeutic agent to the subject.

[0017] Aspects disclosed herein provide methods of treating an inflammatory, a fibrotic, or a fibrostenotic disease or condition in a subject, the method comprising administering to the subject a therapeutically effective amount of an inhibitor of Tumor necrosis factor-like cytokine 1A (TL1A) activity or expression, provided at least three polymorphisms comprising rs1892231, 1556124762, rs6478109, rs2070558, 1s2070561, rs11897732, rs6740739, rs17796285, rs7935393, 1512934476, rs12457255, rs2070557, rs4246905, 1$10974900, rs12434976, 1516901748, 152815844, 1889702, rs2409750, rs1541020, rs4942248, 1512934476, rs12457255, rs2297437, 1541309367, rs10733509, rs10750376, rs10932456, rs1326860, rs1528663, rs951279, rs9806914, 157935393, 151690492, rs420726, 157759385, rs10974900, rs1326860, rs2548147, rs2815844, 15889702, rs9806914, rs7278257, or 111221332, or a proxy polymorphism in linkage disequilibrium therewith as determined with an R? of at least 0.85, or a combination thereof, are detected in a sample obtained from the subject.

[0018] In some embodiments, the at least three polymorphisms comprise: rs6478109, 1556124762, and rs1892231; rs6478109, rs56124762, and rs16901748; rs6478109, 151892231, and rs16901748; rs56124762, rs1892231, and rs16901748; rs6478109, rs2070558, and 151892231; rs6478109, rs2070558, and rs16901748; rs6478109, rs1892231, and rs16901748,; 152070558, rs1892231, and rs16901748; rs6478109, rs2070561, and rs1892231; rs6478109, 152070561 , and rs16901748; rs6478109, rs1892231, and rs16901748; rs2070561, rs1892231, and rs16901748; rs6478109, rs7935393, and rs1892231; rs6478109, rs7935393, and rs9806914; 156478109, rs7935393, and rs7278257; rs6478109, rs7935393, and rs2070557; rs6478109, 181892231, and rs9806914; rs6478109, rs1892231, and rs7278257; rs6478109, rs1892231, and 152070557; 156478109, rs9806914, and rs7278257; rs6478109, rs9806914, and rs2070557, 156478109, rs7278257, and rs2070557; rs7935393, rs1892231, and rs9806914; rs7935393, 181892231, and rs7278257, rs7935393, rs1892231, and rs2070557; rs7935393, rs9806914, and 187278257; 157935393, rs9806914, and rs2070557; rs7935393, 137278257, and rs2070557, 151892231, rs9806914, and rs7278257; rs1892231, rs9806914, and rs2070557; rs1892231, 187278257, and 152070557; or rs9806914, 1s7278257, and rs2070557. In some embodiments, the at least three polymorphisms further comprises a fourth polymorphism comprising rs16901748, 1s1892231, rs56124762, rs6478109, 1s2070558, rs2070561, 1511897732, rs6740739, 1s17796285, 157935393, 1512934476, 1512457255, rs2070557, rs4246905, rs10974900, 1512434976, 152815844, rs889702, rs2409750, 151541020, rs4942248, 1512934476, 112457255, 152297437, 1541309367, rs10733509, rs10750376, rs10932456, rs1326860, rs1528663, rs951279, rs9806914, 157935393, 151690492, 5420726, 157759385, rs10974900, rs1326860, rs2548147, rs2815844, 15889702, rs9806914, rs7278257, or 1s11221332, or a proxy polymorphism in linkage disequilibrium therewith as determined with an R? of at least 0.85, or a combination thereof. In some embodiments, the at least three polymorphisms comprise rs6478109, rs56124762, and 151892231. In some embodiments, the at least three polymorphisms comprise rs6478109, 1$56124762, and rs16901748. In some embodiments, the at least three polymorphisms comprise 1$6478109, 151892231, and rs16901748. In some embodiments, the at least three polymorphisms comprise 1$56124762, rs1892231, and rs16901748. In some embodiments, the proxy polymorphism in linkage disequilibrium is independently associated with a clinical phenotype associated with the inflammatory, the fibrotic, or the fibrostenotic disease or condition in the subject. In some embodiments, the clinical phenotype is stricturing and penetrating disease.

[0019] In some embodiments, the presence of the at least three polymorphisms is predictive that the subject will therapeutically respond to the inhibitor of TL1A at a positive predictive value of at least about 70%. In some embodiments, the presence of the at least three polymorphisms is predictive that the subject will therapeutically respond to the inhibitor of TL1A at a positive predictive value of at least about 75%. In some embodiments, the presence of the at least three polymorphisms is predictive that the subject will therapeutically respond to the inhibitor of TL1A at a positive predictive value of at least about 80%. In some embodiments, the presence of the at least three polymorphisms is predictive that the subject will therapeutically respond to the inhibitor of TL1A at a positive predictive value of at least about 85%. In some embodiments, the presence of the at least three polymorphisms is predictive that the subject will therapeutically respond to the inhibitor of TL1A at a positive predictive value of at least about 90%. In some embodiments, the presence of the at least three polymorphisms is predictive that the subject will therapeutically respond to the inhibitor of TL1A at a positive predictive value of at least about 95%.

[0020] In some embodiments, the presence of the at least three polymorphisms is predictive that the subject will therapeutically respond to the inhibitor of TL1A with a specificity of at least about 70%. In some embodiments, the presence of the at least three polymorphisms is predictive that the subject will therapeutically respond to the inhibitor of TL1A with a specificity of at least about 75%. In some embodiments, the presence of the at least three polymorphisms is predictive that the subject will therapeutically respond to the inhibitor of TL1A with a specificity of at least about 80%. In some embodiments, the presence of the at least three polymorphisms is predictive that the subject will therapeutically respond to the inhibitor of TL1A with a specificity of at least about 85%. In some embodiments, the presence of the at least three polymorphisms is predictive that the subject will therapeutically respond to the inhibitor of TL1A with a specificity of at least about 90%. In some embodiments, the presence of the at least three polymorphisms is predictive that the subject will therapeutically respond to the inhibitor of TL1A with a specificity of at least about 95%.

[0021] In some embodiments, the at least three polymorphisms are detected in the sample by subjecting the sample to an assay configured to detect a presence of at least three nucleotides corresponding to nucleic acid position 501 within SEQ ID NOS: 1-41, or 57-59. In some embodiments, the assay comprises polymerase chain reaction (PCR), quantitative reverse- transcription PCR (qPCR), automated sequencing, or genotype array.

[0022] In some embodiments, the inflammatory, fibrotic, or fibrostenotic disease or condition comprises inflammatory bowel disease, Crohn’s disease, obstructive Crohn’s disease, ulcerative colitis, intestinal fibrosis, intestinal fibrostenosis, rheumatoid arthritis, or primary sclerosing cholangitis. In some embodiments, the Crohn’s disease is ileal, ileocolonic, or colonic Crohn’s disease. In some embodiments, the subject has, or is at risk for developing, a non-response or loss-of-response to a standard therapy comprising glucocorticosteriods, anti-TNF therapy, anti- a4-b7 therapy, anti-IL12p40 therapy, or a combination thereof. In some embodiments, the inhibitor of TL1A is an anti-TL1A antibody or antigen-binding fragment. In some embodiments, the anti-TL1A antibody binds to the same region of human TL1A as a reference antibody selected from Table 2B. In some embodiments, methods further comprise administering an additional therapeutic agent to the subject.

[0023] Aspects disclosed herein provide methods of treating an inflammatory, a fibrotic, or a fibrostenotic disease or condition in a subject, the method comprising: (a) determining whether the subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition is suitable for treatment with an inhibitor of TL1A activity or expression by: (i) obtaining or having obtained a sample from the subject; and (ii) subjecting the sample to an assay adapted to detect at least three polymorphisms that are predictive of the subject exhibiting a therapeutic response to the inhibitor of TL1A activity or expression at a positive predictive value of at least about 70%; and (b) treating the subject by administering a therapeutically effective amount of the inhibitor of TL1A activity or expression to the subject provided the at least three polymorphisms are detected. In some embodiments, the at least three polymorphisms comprise rs1892231, 1556124762, 1rs6478109, rs2070558, rs2070561, rs11897732, rs6740739, 117796285, rs7935393, 1s12934476, 1512457255, 1s2070557, 1s4246905, 1s10974900, rs12434976, 1516901748, rs2815844, rs889702, 152409750, rs1541020, rs4942248, rs12934476, 1512457255, rs2297437, rs41309367, 1510733509, rs10750376, rs10932456, 151326860, 131528663, 1s951279, rs9806914, rs7935393, 151690492, 15420726, rs7759385, rs10974900, 151326860, rs2548147, rs2815844, rs889702, 159806914, rs7278257, rs11221332, or a proxy polymorphism in linkage disequilibrium therewith as determined with an R? of at least 0.85, or a combination thereof.

[0024] In some embodiments, the at least three polymorphisms comprise: rs6478109, 1556124762, and rs1892231; rs6478109, rs56124762, and rs16901748; rs6478109, rs1892231, and rs16901748; rs56124762, rs1892231, and rs16901748; rs6478109, rs2070558, and 151892231; rs6478109, rs2070558, and rs16901748; rs6478109, rs1892231, and rs16901748; 152070558, rs1892231, and rs16901748; rs6478109, rs2070561, and rs1892231; rs6478109, 152070561 , and rs16901748; rs6478109, rs1892231, and rs16901748; rs2070561, rs1892231, and rs16901748; rs6478109, rs7935393, and rs1892231; rs6478109, 1s7935393, and 1s9806914; 156478109, 157935393, and rs7278257; rs6478109, rs7935393, and rs2070557; rs6478109, 151892231, and rs9806914; rs6478109, rs1892231, and rs7278257; rs6478109, rs1892231, and 152070557; rs6478109, rs9806914, and rs7278257; rs6478109, rs9806914, and rs2070557, 156478109, rs7278257, and rs2070557; rs7935393, rs1892231, and rs9806914; rs7935393, 181892231, and rs7278257, rs7935393, rs1892231, and rs2070557; rs7935393, rs9806914, and 157278257, 157935393, 159806914, and rs2070557; 157935393, 57278257, and rs2070557, 1s1892231, rs9806914, and rs7278257; rs1892231, rs9806914, and rs2070557; rs1892231, 187278257, and 152070557, or rs9806914, 1s7278257, and rs2070557. In some embodiments, the at least three polymorphisms further comprises a fourth polymorphism comprising rs16901748, 151892231, rs56124762, 1s6478109, 152070558, rs2070561, 1511897732, rs6740739, rs17796285, 187935393, 1512934476, 1312457255, rs2070557, rs4246905, rs10974900, rs12434976, 152815844, rs889702, rs2409750, 151541020, rs4942248, 1512934476, 112457255, 152297437, 1541309367, rs10733509, rs10750376, 1s10932456, rs1326860, rs1528663, rs951279, rs9806914, 157935393, rs1690492, rs420726, 157759385, rs10974900, rs1326860, rs2548147, rs2815844, 1s889702, rs9806914, rs7278257, or rs11221332 or a proxy polymorphism in linkage disequilibrium therewith as determined with an R? of at least 0.85, or a combination thereof. In some embodiments, the at least three polymorphisms comprise rs6478109, rs56124762, and rs1892231. In some embodiments, the at least three polymorphisms comprise rs6478109, 1556124762, and rs16901748. In some embodiments, the at least three polymorphisms comprise 1$6478109, 151892231, and rs16901748. In some embodiments, the at least three polymorphisms comprise 1556124762, rs1892231, and rs16901748.

[0025] In some embodiments, the at least three polymorphisms are predictive that the subject will therapeutically respond to the inhibitor of TL1A at a positive predictive value of at least about 70%. In some embodiments, the at least three polymorphisms are predictive that the subject will therapeutically respond to the inhibitor of TL1A at a positive predictive value of at least about 75%. In some embodiments, the at least three polymorphisms are predictive that the subject will therapeutically respond to the inhibitor of TL1A at a positive predictive value of at least about 80%. In some embodiments, the at least three polymorphisms are predictive that the subject will therapeutically respond to the inhibitor of TL1A at a positive predictive value of at least about 85%. In some embodiments, the at least three polymorphisms are predictive that the subject will therapeutically respond to the inhibitor of TL1A at a positive predictive value of at least about 90%. In some embodiments, the at least three polymorphisms are predictive that the subject will therapeutically respond to the inhibitor of TL1A at a positive predictive value of at least about 95%

[0026] In some embodiments, the at least three polymorphisms are predictive that the subject will therapeutically respond to the inhibitor of TL1A with a specificity of at least about 70%. In some embodiments, the at least three polymorphisms are predictive that the subject will therapeutically respond to the inhibitor of TL1A with a specificity of at least about 75%. In some embodiments, the at least three polymorphisms are predictive that the subject will therapeutically respond to the inhibitor of TL1A with a specificity of at least about 80%. In some embodiments, the at least three polymorphisms are predictive that the subject will therapeutically respond to the inhibitor of TL1A with a specificity of at least about 85%. In some embodiments, the at least three polymorphisms are predictive that the subject will therapeutically respond to the inhibitor of TL1A with a specificity of at least about 90%. In some embodiments, the at least three polymorphisms are predictive that the subject will therapeutically respond to the inhibitor of TL1A with a specificity of at least about 95%.

[0027] In some embodiments, the inflammatory, fibrotic, or fibrostenotic disease or condition comprises inflammatory bowel disease, Crohn’s disease, obstructive Crohn’s disease, ulcerative colitis, intestinal fibrosis, intestinal fibrostenosis, rheumatoid arthritis, or primary sclerosing cholangitis. In some embodiments, the Crohn’s disease is ileal, ileocolonic, or colonic Crohn’s disease. In some embodiments, the wherein the inhibitor of TL1A activity or expression is an anti-TL1A antibody or antigen-binding fragment. In some embodiments, the anti-TL1A antibody binds to the same region of human TL1A as a reference antibody selected from Table 2B. In some embodiments, methods further comprise administering an additional therapeutic agent to the subject.

[0028] In some embodiments, the subject is at risk of developing a non-response or loss-of- response to a standard therapy comprising glucocorticosteriods, anti-TNF therapy, anti-a4-b7 therapy, anti-IL12p40 therapy, or a combination thereof. In some embodiments, the proxy polymorphism in linkage disequilibrium is independently associated with a clinical phenotype associated with the inflammatory, the fibrotic, or the fibrostenotic disease or condition in the subject. In some embodiments, the clinical phenotype is stricturing and penetrating disease.

[0029] Aspects disclosed herein provide methods of treating an inflammatory, a fibrotic, or a fibrostenotic disease or condition in a subject, the method comprising: (a) determining whether the subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition is suitable for treatment with an inhibitor of TL1A activity or expression by: (i) obtaining or having obtained a sample from the subject; and (ii) subjecting the sample to an assay adapted to detect at least three polymorphisms comprising rs1892231, rs56124762, rs6478109, rs2070558, rs2070561, 1511897732, rs6740739, rs17796285, rs7935393, 1512934476, 1512457255, rs2070557, 154246905, 1510974900, 1512434976, 1516901748, 152815844, 1s889702, rs2409750, rs1541020, 154942248, 1512934476, 1512457255, 152297437, rs41309367, 1510733509, rs10750376, 1510932456, 131326860, 151528663, 1s951279, 159806914, rs7935393, rs1690492, rs420726, 157759385, rs10974900, 151326860, 152548147, 152815844, 15889702, rs9806914, rs7278257, 1rs11221332, or a proxy polymorphism in linkage disequilibrium therewith as determined with an R? of at least 0.85, or a combination thereof; and (b) treating the subject by administering a therapeutically effective amount of the inhibitor of TL1A activity or expression to the subject.

[0030] In some embodiments, the at least three polymorphisms comprise: rs6478109, 1556124762, and rs1892231; rs6478109, rs56124762, and rs16901748; rs6478109, rs1892231, and rs16901748; rs56124762, rs1892231, and rs16901748; rs6478109, rs2070558, and 151892231; rs6478109, rs2070558, and rs16901748; rs6478109, rs1892231, and rs16901748,; 152070558, 151892231, and rs16901748; rs6478109, rs2070561, and rs1892231; rs6478109, 1s2070561 , and rs16901748; rs6478109, rs1892231, and rs16901748; rs2070561, rs1892231, and rs16901748; rs6478109, rs7935393, and rs1892231; rs6478109, rs7935393, and rs9806914; 156478109, 157935393, and rs7278257; rs6478109, rs7935393, and rs2070557; rs6478109, 151892231, and rs9806914; rs6478109, rs1892231, and rs7278257; rs6478109, rs1892231, and 152070557; 156478109, rs9806914, and rs7278257; rs6478109, rs9806914, and rs2070557, 156478109, rs7278257, and rs2070557; rs7935393, rs1892231, and rs9806914; rs7935393, 181892231, and rs7278257, rs7935393, rs1892231, and rs2070557; rs7935393, rs9806914, and 187278257; 157935393, rs9806914, and rs2070557; rs7935393, 157278257, and rs2070557, 151892231, rs9806914, and rs7278257; rs1892231, rs9806914, and rs2070557; rs1892231, 187278257, and 152070557; or rs9806914, rs7278257, and rs2070557. In some embodiments, the at least three polymorphisms further comprises a fourth polymorphism comprising rs16901748, 151892231, 1556124762, rs6478109, rs2070558, rs2070561, rs11897732, rs6740739, rs17796285, 157935393, 1512934476, 1512457255, rs2070557, rs4246905, rs10974900, 1512434976, 152815844, 1s889702, rs2409750, rs1541020, rs4942248, 1512934476, rs12457255, rs2297437, 1541309367, rs10733509, rs10750376, rs10932456, rs1326860, rs1528663, rs951279, rs9806914, 157935393, rs1690492, rs420726, 157759385, rs10974900, rs1326860, rs2548147, rs2815844, 1s889702, rs9806914, rs7278257, or rs11221332 or a proxy polymorphism in linkage disequilibrium therewith as determined with an R? of at least 0.85, or a combination thereof. In some embodiments, the at least three polymorphisms comprise rs6478109, rs56124762, and 151892231. In some embodiments, the at least three polymorphisms comprise rs6478109, 1556124762, and rs16901748. In some embodiments, the at least three polymorphisms comprise 156478109, 151892231, and rs16901748. In some embodiments, the at least three polymorphisms comprise 1556124762, rs1892231, and rs16901748.

[0031] In some embodiments, the at least three polymorphisms are predictive that the subject will therapeutically respond to the inhibitor of TL1A at a positive predictive value of at least about 70%. In some embodiments, the at least three polymorphisms are predictive that the subject will therapeutically respond to the inhibitor of TL1A at a positive predictive value of at least about 75%. In some embodiments, the at least three polymorphisms are predictive that the subject will therapeutically respond to the inhibitor of TL1A at a positive predictive value of at least about 80%. In some embodiments, the at least three polymorphisms are predictive that the subject will therapeutically respond to the inhibitor of TL1A at a positive predictive value of at least about 85%. In some embodiments, the at least three polymorphisms are predictive that the subject will therapeutically respond to the inhibitor of TL1A at a positive predictive value of at least about 90%. In some embodiments, the at least three polymorphisms are predictive that the subject will therapeutically respond to the inhibitor of TL1A at a positive predictive value of at least about 95%.

[0032] In some embodiments, the at least three polymorphisms are predictive that the subject will therapeutically respond to the inhibitor of TL1A with a specificity of at least about 70%. In some embodiments, the at least three polymorphisms are predictive that the subject will therapeutically respond to the inhibitor of TL1A with a specificity of at least about 75%. In some embodiments, the at least three polymorphisms are predictive that the subject will therapeutically respond to the inhibitor of TL1A with a specificity of at least about 80%. In some embodiments, the at least three polymorphisms are predictive that the subject will therapeutically respond to the inhibitor of TL1A with a specificity of at least about 85%. In some embodiments, the at least three polymorphisms are predictive that the subject will therapeutically respond to the inhibitor of TL1A with a specificity of at least about 90%. In some embodiments, the at least three polymorphisms are predictive that the subject will therapeutically respond to the inhibitor of TL1A with a specificity of at least about 95%.

[0033] In some embodiments, the inflammatory, fibrotic, or fibrostenotic disease or condition comprises inflammatory bowel disease, Crohn’s disease, obstructive Crohn’s disease, ulcerative colitis, intestinal fibrosis, intestinal fibrostenosis, rheumatoid arthritis, or primary sclerosing cholangitis. In some embodiments, the Crohn’s disease is ileal, ileocolonic, or colonic Crohn’s disease.

[0034] In some embodiments, the wherein the inhibitor of TL1A activity or expression is an anti-TL1A antibody or antigen-binding fragment. In some embodiments, the anti-TL1A antibody binds to the same region of human TL1A as a reference antibody selected from Table 2B. In some embodiments, methods further comprise administering an additional therapeutic agent to the subject.

[0035] In some embodiments, the subject is at risk of developing a non-response or loss-of- response to a standard therapy comprising glucocorticosteriods, anti-TNF therapy, anti-a4-b7 therapy, anti-IL12p40 therapy, or a combination thereof. In some embodiments, the proxy polymorphism in linkage disequilibrium is independently associated with a clinical phenotype associated with the inflammatory, the fibrotic, or the fibrostenotic disease or condition in the subject. In some embodiments, the clinical phenotype is stricturing and penetrating disease.

[0036] Aspects disclosed herein provide methods of treating an inflammatory, a fibrotic, or a fibrostenotic disease or condition in a subject, the method comprising administering to the subject a therapeutically effective amount of an inhibitor of TL1A activity or expression, wherein the subject expresses at least three polymorphisms comprising rs16901748, rs6478109, 1$56124762, or a proxy polymorphism in linkage disequilibrium therewith as determined with an R? of at least 0.85. In some embodiments, the at least three polymorphisms further comprises a fourth polymorphism comprising rs16901748, rs1892231, rs56124762, rs6478109, rs2070558, 152070561, rs11897732, rs6740739, 1517796285, rs7935393, 1512934476, 1512457255, 152070557, 154246905, rs10974900, rs12434976, 152815844, rs889702, 1s2409750, rs1541020, 154942248, 1512934476, 1512457255, rs2297437, rs41309367, 1510733509, rs10750376, 1510932456, 131326860, 151528663, 1s951279, 159806914, rs7935393, rs1690492, rs420726, 157759385, 1510974900, 51326860, 152548147, 152815844, 1s889702, rs9806914, 157278257, or 1rs11221332 or a proxy polymorphism in linkage disequilibrium therewith as determined with an R? of at least 0.85, or a combination thereof. In some embodiments, the at least three polymorphisms are predictive that the subject will therapeutically respond to the inhibitor of TLI1A at a positive predictive value of at least about 70%. In some embodiments, the at least three polymorphisms are predictive that the subject will therapeutically respond to the inhibitor of TL1A at a positive predictive value of at least about 75%. In some embodiments, the at least three polymorphisms are predictive that the subject will therapeutically respond to the inhibitor of TL1A at a positive predictive value of at least about 80%. In some embodiments, the at least three polymorphisms are predictive that the subject will therapeutically respond to the inhibitor of TL1A at a positive predictive value of at least about 85%. In some embodiments, the at least three polymorphisms are predictive that the subject will therapeutically respond to the inhibitor of TL1A at a positive predictive value of at least about 90%. In some embodiments, the at least three polymorphisms are predictive that the subject will therapeutically respond to the inhibitor of TL1A at a positive predictive value of at least about 95%. In some embodiments, the at least three polymorphisms are predictive that the subject will therapeutically respond to the inhibitor of TL1A with a specificity of at least about 70%. In some embodiments, the at least three polymorphisms are predictive that the subject will therapeutically respond to the inhibitor of TL1A with a specificity of at least about 75%. In some embodiments, the at least three polymorphisms are predictive that the subject will therapeutically respond to the inhibitor of TLI1A with a specificity of at least about 80%. In some embodiments, the at least three polymorphisms are predictive that the subject will therapeutically respond to the inhibitor of TLI1A with a specificity of at least about 85%. In some embodiments, the at least three polymorphisms are predictive that the subject will therapeutically respond to the inhibitor of TL1A with a specificity of at least about 90%. In some embodiments, the at least three polymorphisms are predictive that the subject will therapeutically respond to the inhibitor of TL1A with a specificity of at least about 95% .=In some embodiments, the inflammatory, fibrotic, or fibrostenotic disease or condition comprises inflammatory bowel disease, Crohn’s disease, obstructive Crohn’s disease, ulcerative colitis, intestinal fibrosis, intestinal fibrostenosis, rheumatoid arthritis, or primary sclerosing cholangitis. In some embodiments, the Crohn’s disease is ileal, ileocolonic, or colonic Crohn’s disease. In some embodiments, the wherein the inhibitor of TL1A activity or expression is an anti-TL1A antibody or antigen-binding fragment. In some embodiments, the anti-TL1A antibody binds to the same region of human TL1A as a reference antibody selected from Table 2B. In some embodiments, methods further comprise administering an additional therapeutic agent to the subject. In some embodiments, the subject is at risk of developing a non-response or loss-of-response to a standard therapy comprising glucocorticosteriods, anti-TNF therapy, anti-a4-b7 therapy, anti-IL12p40 therapy, or a combination thereof. In some embodiments, the proxy polymorphism in linkage disequilibrium is independently associated with a clinical phenotype associated with the inflammatory, the fibrotic, or the fibrostenotic disease or condition in the subject. In some embodiments, the clinical phenotype is stricturing and penetrating disease.

[0037] Aspects disclosed herein provide methods comprising: (a) providing a sample obtained from a subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition; and (b) detecting a presence of at least three polymorphisms in the sample with a genotyping assay, wherein the presence of the at least three polymorphisms is predictive of a therapeutic response in the subject to a treatment with an inhibitor of TL1A activity or expression at a positive predictive value of at least about 70%. In some embodiments, the at least three polymorphisms comprise rs1892231, 1s56124762, rs6478109, rs2070558, rs2070561, 1511897732, rs6740739, rs17796285, rs7935393, 1512934476, 1s12457255, rs2070557, 154246905, 1510974900, 1512434976, 1516901748, 152815844, 1s889702, rs2409750, rs1541020, 154942248, 1512934476, 1512457255, rs2297437, rs41309367, 1510733509, rs10750376, 1510932456, rs1326860, 151528663, 1s951279, 159806914, rs7935393, rs1690492, rs420726, 157759385, rs10974900, 151326860, 152548147, 152815844, 15889702, rs9806914, rs7278257, 1s11221332, or a proxy polymorphism in linkage disequilibrium therewith as determined with an RZ of at least 0.85, or a combination thereof.

[0038] In some embodiments, detecting the at least three polymorphisms comprises detecting at least three genotypes corresponding to nucleic acid position 501 within at least three of SEQ ID NOS: 1-41, or 57-59. In some embodiments, the presence of at least three polymorphisms is predictive that the subject will therapeutically respond to the inhibitor of TL1A at a positive predictive value of at least about 75%. In some embodiments, the presence of at least three polymorphisms is predictive that the subject will therapeutically respond to the inhibitor of TL1A at a positive predictive value of at least about 80%. In some embodiments, the presence of at least three polymorphisms is predictive that the subject will therapeutically respond to the inhibitor of TL1A at a positive predictive value of at least about 85%. In some embodiments, the presence of at least three polymorphisms is predictive that the subject will therapeutically respond to the inhibitor of TL1A at a positive predictive value of at least about 90%. In some embodiments, the presence of at least three polymorphisms is predictive that the subject will therapeutically respond to the inhibitor of TL1A at a positive predictive value of at least about 95%,

[0039] In some embodiments, the presence of at least three polymorphisms is predictive that the subject will therapeutically respond to the inhibitor of TL1A with a specificity of at least about 70%. In some embodiments, the presence of at least three polymorphisms is predictive that the subject will therapeutically respond to the inhibitor of TL1A with a specificity of at least about 75%. In some embodiments, the presence of at least three polymorphisms is predictive that the subject will therapeutically respond to the inhibitor of TL1A with a specificity of at least about 80%. In some embodiments, the presence of at least three polymorphisms is predictive that the subject will therapeutically respond to the inhibitor of TL1A with a specificity of at least about 85%. In some embodiments, the presence of at least three polymorphisms is predictive that the subject will therapeutically respond to the inhibitor of TL1A with a specificity of at least about 90%. In some embodiments, the presence of at least three polymorphisms is predictive that the subject will therapeutically respond to the inhibitor of TL1A with a specificity of at least about 95%.

[0040] In some embodiments, methods further comprise administering to the subject a therapeutically effective amount of the inhibitor of TL1A activity or expression to treat the inflammatory, fibrotic, or fibrostenotic disease or condition. In some embodiments, the subject is at risk of developing a non-response or loss-of-response to a standard therapy comprising glucocorticosteriods, anti-TNF therapy, anti-a4-b7 therapy, anti-IL12p40 therapy, or a combination thereof. In some embodiments, the inflammatory, fibrotic, or fibrostenotic disease or condition comprises inflammatory bowel disease, Crohn’s disease, obstructive Crohn’s disease, ulcerative colitis, intestinal fibrosis, intestinal fibrostenosis, rheumatoid arthritis, or primary sclerosing cholangitis. In some embodiments, the Crohn’s disease is ileal, ileocolonic, or colonic Crohn’s disease.

[0041] In some embodiments, the wherein the inhibitor of TL1A activity or expression is an anti-TL1A antibody or antigen-binding fragment. In some embodiments, the anti-TL1A antibody binds to the same region of human TL1A as a reference antibody selected from Table 2B. In some embodiments, methods further comprise administering an additional therapeutic agent to the subject.

[0042] In some embodiments, the at least three polymorphisms comprise: rs6478109, 1556124762, and rs1892231; rs6478109, rs56124762, and rs16901748; rs6478109, rs1892231, and rs16901748; rs56124762, rs1892231, and rs16901748; rs6478109, rs2070558, and 181892231; rs6478109, rs2070558, and rs16901748; rs6478109, rs1892231, and rs16901748,; 1$2070558, rs1892231, and rs16901748; rs6478109, rs2070561, and rs1892231; rs6478109, 1$2070561 , and rs16901748; rs6478109, rs1892231, and rs16901748; rs2070561, rs1892231, and rs16901748; rs6478109, rs7935393, and rs1892231; rs6478109, 1s7935393, and rs9806914; 156478109, 157935393, and rs7278257; rs6478109, rs7935393, and 152070557; rs6478109, 151892231, and rs9806914; rs6478109, rs1892231, and rs7278257; rs6478109, rs1892231, and 152070557; rs6478109, rs9806914, and rs7278257; rs6478109, rs9806914, and rs2070557; 156478109, rs7278257, and rs2070557; rs7935393, rs1892231, and rs9806914; rs7935393, 181892231, and rs7278257, rs7935393, rs1892231, and rs2070557; rs7935393, rs9806914, and 187278257; 157935393, rs9806914, and rs2070557; rs7935393, 157278257, and rs2070557, 181892231, rs9806914, and rs7278257; rs1892231, rs9806914, and rs2070557; rs1892231, 187278257, and rs2070557; or rs9806914, rs7278257, and rs2070557. In some embodiments, the at least three polymorphisms further comprises a fourth polymorphism comprising rs16901748, 151892231, rs56124762, rs6478109, rs2070558, rs2070561, rs11897732, rs6740739, rs17796285, 157935393, 1512934476, rs12457255, rs2070557, rs4246905, 1510974900, 1512434976, 152815844, 1889702, rs2409750, rs1541020, rs4942248, 1512934476, rs12457255, rs2297437, 1541309367, rs10733509, rs10750376, rs10932456, rs1326860, rs1528663, rs951279, rs9806914, 157935393, 151690492, rs420726, 157759385, rs10974900, rs1326860, rs2548147, rs2815844, 1$889702, rs9806914, rs7278257, or rs11221332, or a combination thereof. In some embodiments, the at least three polymorphisms comprise rs6478109, rs56124762, and 1rs1892231. In some embodiments, the at least three polymorphisms comprise rs6478109, 1$56124762, and rs16901748. In some embodiments, the at least three polymorphisms comprise 156478109, rs1892231, and rs16901748. In some embodiments, the at least three polymorphisms comprise 1$56124762, rs1892231, and rs16901748. In some embodiments, the proxy polymorphism in linkage disequilibrium is independently associated with a clinical phenotype associated with the inflammatory, the fibrotic, or the fibrostenotic disease or condition in the subject. In some embodiments, the clinical phenotype is stricturing and penetrating disease.

[0043] Aspects disclosed herein provide methods comprising: (a) providing a sample obtained from a subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition; and (b) detecting a presence of at least three polymorphisms in the sample with a genotyping assay, said at least three polymorphisms comprising rs1892231, rs56124762, rs6478109, 152070558, 152070561, rs11897732, 156740739, rs17796285, 137935393, rs12934476, 1512457255, rs2070557, rs4246905, rs10974900, rs12434976, 1516901748, rs2815844, rs889702, 152409750, 151541020, rs4942248, 1512934476, 1812457255, rs2297437, rs41309367, 1510733509, rs10750376, rs10932456, rs1326860, 151528663, 15951279, rs9806914, rs7935393, 151690492, 15420726, rs7759385, 1s10974900, 51326860, rs2548147, rs2815844, rs889702, 159806914, 157278257, 1511221332, or a proxy polymorphism in linkage disequilibrium therewith as determined with an R2 of at least 0.85, or a combination thereof.

[0044] In some embodiments, detecting the at least three polymorphisms comprises detecting at least three genotypes corresponding to nucleic acid position 501 within at least three of SEQ ID NOS: 1-41, or 57-59. In some embodiments, the presence of at least three polymorphisms is predictive of a therapeutic response in a subject to a treatment with the inhibitor of TL1A ata positive predictive value of at least about 70%. In some embodiments, the presence of at least three polymorphisms is predictive of a therapeutic response in a subject to a treatment with the inhibitor of TL1A at a positive predictive value of at least about 75%. In some embodiments, the presence of at least three polymorphisms is predictive of a therapeutic response in a subject to a treatment with the inhibitor of TL1A at a positive predictive value of at least about 80%. In some embodiments, the presence of at least three polymorphisms is predictive of a therapeutic response in a subject to a treatment with the inhibitor of TL1A at a positive predictive value of at least about 85%. In some embodiments, the presence of at least three polymorphisms is predictive of a therapeutic response in a subject to a treatment with the inhibitor of TL1A at a positive predictive value of at least about 90%. In some embodiments, the presence of at least three polymorphisms is predictive of a therapeutic response in a subject to a treatment with the inhibitor of TL1A ata positive predictive value of at least about 95%.

[0045] In some embodiments, the presence of at least three polymorphisms is predictive of a therapeutic response in a subject to a treatment with the inhibitor of TL1A with a specificity of at least about 70%. In some embodiments, the presence of at least three polymorphisms is predictive of a therapeutic response in a subject to a treatment with the inhibitor of TL1A with a specificity of at least about 75%. In some embodiments, the presence of at least three polymorphisms is predictive of a therapeutic response in a subject to a treatment with the inhibitor of TL1A with a specificity of at least about 80%. In some embodiments, the presence of at least three polymorphisms is predictive of a therapeutic response in a subject to a treatment with the inhibitor of TL1A with a specificity of at least about 85%. In some embodiments, the presence of at least three polymorphisms is predictive of a therapeutic response in a subject to a treatment with the inhibitor of TL1A with a specificity of at least about 90%. In some embodiments, the presence of at least three polymorphisms is predictive of a therapeutic response in a subject to a treatment with the inhibitor of TL1A with a specificity of at least about 95%.

[0046] In some embodiments, methods further comprise administering to the subject a therapeutically effective amount of the inhibitor of TL1A activity or expression to treat the inflammatory, fibrotic, or fibrostenotic disease or condition. In some embodiments, the subject is at risk of developing a non-response or loss-of-response to a standard therapy comprising glucocorticosteriods, anti-TNF therapy, anti-a4-b7 therapy, anti-IL12p40 therapy, or a combination thereof. In some embodiments, the inflammatory, fibrotic, or fibrostenotic disease or condition comprises inflammatory bowel disease, Crohn’s disease, obstructive Crohn’s disease, ulcerative colitis, intestinal fibrosis, intestinal fibrostenosis, rheumatoid arthritis, or primary sclerosing cholangitis. In some embodiments, the Crohn’s disease is ileal, ileocolonic, or colonic Crohn’s disease.

[0047] In some embodiments, the wherein the inhibitor of TL1A activity or expression is an anti-TL1A antibody or antigen-binding fragment. In some embodiments, the anti-TL1A antibody binds to the same region of human TL1A as a reference antibody selected from Table 2B. In some embodiments, methods further comprise administering an additional therapeutic agent to the subject.

[0048] In some embodiments, the at least three polymorphisms comprise: rs6478109, 1856124762, and 1s1892231; rs6478109, rs56124762, and rs16901748; rs6478109, rs1892231, and rs16901748; rs56124762, rs1892231, and rs16901748; rs6478109, rs2070558, and 151892231; 1s6478109, rs2070558, and rs16901748; rs6478109, rs1892231, and rs16901748,; 1$2070558, rs1892231, and rs16901748; rs6478109, rs2070561, and rs1892231; rs6478109, 1s2070561 , and rs16901748; rs6478109, rs1892231, and rs16901748; rs2070561, rs1892231, and rs16901748; rs6478109, rs7935393, and rs1892231; rs6478109, rs7935393, and rs9806914; 156478109, rs7935393, and rs7278257; rs6478109, rs7935393, and rs2070557; rs6478109, 151892231, and rs9806914; rs6478109, rs1892231, and rs7278257; rs6478109, rs1892231, and 152070557; 156478109, rs9806914, and rs7278257; rs6478109, rs9806914, and rs2070557, 156478109, rs7278257, and rs2070557; rs7935393, rs1892231, and rs9806914; rs7935393, 1$1892231, and rs7278257, 1s7935393, rs1892231, and rs2070557; rs7935393, rs9806914, and 187278257; 157935393, rs9806914, and rs2070557; rs7935393, 57278257, and rs2070557, 151892231, 159806914, and rs7278257; rs1892231, rs9806914, and rs2070557; rs1892231, 187278257, and rs2070557, or rs9806914, rs7278257, and rs2070557. In some embodiments, the at least three polymorphisms further comprises a fourth polymorphism comprising rs16901748, 151892231, 1556124762, rs6478109, rs2070558, rs2070561, rs11897732, rs6740739, rs17796285, 157935393, 1512934476, rs12457255, rs2070557, rs4246905, rs10974900, 1512434976, 152815844, rs889702, rs2409750, rs1541020, rs4942248, 1512934476, rs12457255, rs2297437, 1541309367, rs10733509, rs10750376, rs10932456, rs1326860, rs1528663, rs951279, rs9806914, 157935393, rs1690492, rs420726, 157759385, rs10974900, rs1326860, rs2548147, rs2815844, 1$889702, rs9806914, rs7278257, or rs11221332, or a combination thereof. In some embodiments, the at least three polymorphisms comprise rs6478109, rs56124762, and 151892231. In some embodiments, the at least three polymorphisms comprise rs6478109, 1556124762, and rs16901748. In some embodiments, the at least three polymorphisms comprise 156478109, 151892231, and rs16901748. In some embodiments, the at least three polymorphisms comprise 1$56124762, rs1892231, and rs16901748. In some embodiments, the proxy polymorphism in linkage disequilibrium is independently associated with a clinical phenotype associated with the inflammatory, the fibrotic, or the fibrostenotic disease or condition in the subject. In some embodiments, the clinical phenotype is stricturing and penetrating disease.

[0049] Aspects disclosed herein provide computer-implemented methods comprising: (a) receiving genotype data of a subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition; and (b) analyzing the genotype data to detect a presence of at least three genotypes predictive of a therapeutic response in the subject to a treatment with an inhibitor of Tumor necrosis factor-like cytokine 1A (TL1A) activity or expression to treat the inflammatory, the fibrotic, or the fibrostenotic disease or condition with a positive predictive value of at least about 70%. In some embodiments, the at least three genotypes comprise at least three polymorphisms comprising rs1892231, rs56124762, rs6478109, rs2070558, rs2070561, rs11897732, rs6740739, 1517796285, 1s7935393, 1512934476, rs12457255, 152070557, 154246905, 1510974900, 1512434976, 116901748, rs2815844, rs889702, rs2409750, 151541020, rs4942248, rs12934476, 1512457255, 1s2297437, 1541309367, rs10733509, 1510750376, rs10932456, 151326860, 151528663, rs951279, rs9806914, 157935393, 151690492, 15420726, rs7759385, rs10974900, 151326860, rs2548147, 152815844, rs889702, rs9806914, rs7278257, or rs11221332, or a proxy polymorphism in linkage disequilibrium therewith as determined with an R? of at least 0.85, or a combination thereof

[0050] In some embodiments, methods further comprise generating a TNFSF15 profile comprising a positive, a negative, or an indeterminant result for a therapeutic response to a treatment with the inhibitor of TL1A activity or expression.

[0051] In some embodiments, determining the likelihood that the subject will therapeutically respond to the treatment with the inhibitor of TL1A activity or expression is performed at a positive predictive value of at least about 70%. In some embodiments, determining the likelihood that the subject will therapeutically respond to the treatment with the inhibitor of TL1A activity or expression is performed at a positive predictive value of at least about 75%. In some embodiments, determining the likelihood that the subject will therapeutically respond to the treatment with the inhibitor of TL1A activity or expression is performed at a positive predictive value of at least about 80%. In some embodiments, determining the likelihood that the subject will therapeutically respond to the treatment with the inhibitor of TL1A activity or expression is performed at a positive predictive value of at least about 85%. In some embodiments, determining the likelihood that the subject will therapeutically respond to the treatment with the inhibitor of TL1A activity or expression is performed at a positive predictive value of at least about 90%. In some embodiments, determining the likelihood that the subject will therapeutically respond to the treatment with the inhibitor of TL1A activity or expression is performed at a positive predictive value of at least about 95%.

[0052] In some embodiments, determining the likelihood that the subject will therapeutically respond to the treatment with the inhibitor of TL1A activity or expression is performed at with a specificity of at least about 70%. In some embodiments, determining the likelihood that the subject will therapeutically respond to the treatment with the inhibitor of TL1A activity or expression is performed at with a specificity of at least about 75%. In some embodiments, determining the likelihood that the subject will therapeutically respond to the treatment with the inhibitor of TL1A activity or expression is performed at with a specificity of at least about 80%. In some embodiments, determining the likelihood that the subject will therapeutically respond to the treatment with the inhibitor of TL1A activity or expression is performed at with a specificity of at least about 85%. In some embodiments, determining the likelihood that the subject will therapeutically respond to the treatment with the inhibitor of TL1A activity or expression is performed at with a specificity of at least about 90%. In some embodiments, determining the likelihood that the subject will therapeutically respond to the treatment with the inhibitor of TLI1A activity or expression is performed at with a specificity of at least about 95%.

[0053] In some embodiments, the at least three polymorphisms comprise: rs6478109, 1556124762, and rs1892231; rs6478109, rs56124762, and rs16901748; rs6478109, rs1892231, and rs16901748; rs56124762, rs1892231, and rs16901748; rs6478109, rs2070558, and 151892231; rs6478109, rs2070558, and rs16901748; rs6478109, rs1892231, and rs16901748,; 152070558, 151892231, and rs16901748; rs6478109, rs2070561, and rs1892231; rs6478109, 1s2070561 , and rs16901748; rs6478109, rs1892231, and rs16901748; rs2070561, rs1892231, and rs16901748; rs6478109, rs7935393, and rs1892231; rs6478109, rs7935393, and 159806914; 156478109, 157935393, and rs7278257; rs6478109, rs7935393, and rs2070557; rs6478109, 151892231, and rs9806914; rs6478109, rs1892231, and rs7278257; rs6478109, rs1892231, and 152070557; rs6478109, rs9806914, and rs7278257; rs6478109, rs9806914, and rs2070557; 156478109, rs7278257, and rs2070557; rs7935393, rs1892231, and rs9806914; rs7935393, 181892231, and rs7278257, rs7935393, rs1892231, and rs2070557; rs7935393, rs9806914, and 187278257; 157935393, rs9806914, and rs2070557; rs7935393, 157278257, and rs2070557, 151892231, rs9806914, and rs7278257; rs1892231, rs9806914, and rs2070557; rs1892231, 187278257, and 152070557; or rs9806914, rs7278257, and rs2070557. In some embodiments, the at least three polymorphisms further comprises a fourth polymorphism comprising rs16901748, 151892231, 1556124762, rs6478109, rs2070558, rs2070561, rs11897732, rs6740739, rs17796285, 157935393, 1512934476, 1512457255, rs2070557, rs4246905, rs10974900, 1512434976, 152815844, 1s889702, rs2409750, rs1541020, rs4942248, 1512934476, rs12457255, rs2297437, 1541309367, rs10733509, rs10750376, rs10932456, rs1326860, rs1528663, rs951279, rs9806914, 157935393, rs1690492, rs420726, 157759385, rs10974900, rs1326860, rs2548147, rs2815844, 1s889702, rs9806914, rs7278257, or 111221332, or a proxy polymorphism in linkage disequilibrium therewith as determined with an R? of at least 0.85, or a combination thereof. In some embodiments, the at least three polymorphisms comprise rs6478109, rs56124762, and 151892231. In some embodiments, the at least three polymorphisms comprise rs6478109, 1s56124762, and rs16901748. In some embodiments, the at least three polymorphisms comprise rs6478109, rs1892231, and rs16901748. In some embodiments, the at least three polymorphisms comprise 1556124762, rs1892231, and rs16901748.

[0054] In some embodiments, methods further comprise generating a report comprising the TNFSF15 profile for display to a user. In some embodiments, the inflammatory, the fibrotic, and the fibrostenotic disease or condition comprises inflammatory bowel disease, Crohn’s disease, obstructive Crohn’s disease, ulcerative colitis, intestinal fibrosis, intestinal fibrostenosis, rheumatoid arthritis, or primary sclerosing cholangitis. In some embodiments, the Crohn’s disease is ileal, ileocolonic, or colonic Crohn’s disease. In some embodiments, the inhibitor of TL1A activity or expression is an anti-TL1A antibody or antigen-binding fragment. In some embodiments, the anti-TL1A antibody binds to the same region of human TL1A as a reference antibody selected from Table 2B. In some embodiments, the proxy polymorphism in linkage disequilibrium is independently associated with a clinical phenotype associated with the inflammatory, the fibrotic, or the fibrostenotic disease or condition in the subject. In some embodiments, the clinical phenotype is stricturing and penetrating disease.

[0055] Aspects disclosed herein provide kits comprising: (a) at least three primer pairs, each primer pair comprising a first primer and a second primer, where said first primer comprises at least 10 contiguous nucleic acids corresponding to nucleotides 4090-500 of SEQ ID NOS: 1-41, or 57-59, and wherein said second primer comprises at least 10 contiguous nucleic acids corresponding to nucleotides 4090-500 of a reverse complement to SEQ ID NOS: 1-41, or 57-59; and (b) at least three polynucleotide molecules, each polynucleotide molecule comprising a detectable moiety, wherein the polynucleotide molecule comprises a nucleic acid sequence comprising a nucleotide corresponding to nucleotide position 501 of SEQ ID NOS: 1-41, or 57- 59. In some embodiments, the kit is useful for selecting a patient with an inflammatory, a fibrotic, or a fibrostenotic disease or condition for treatment with an inhibitor of TL1A activity or expression, provided the presence of the at least three polymorphisms is detected in a sample obtained from the patient.

[0056] Aspects disclosed herein provide kits comprising: (a) a first primer pair comprising a first forward primer provided in any one of SEQ ID NOS: 364101-364110 and a corresponding first reverse primer provided in SEQ ID NO: in any one of SEQ ID NOS: 364111-364120; (b) a second primer pair comprising a second forward primer provided in any one of SEQ ID NOS: 364101-364110 and a corresponding second reverse primer provided in any one of SEQ ID NOS: 364111-364120; (c) a third primer pair comprising a third forward primer provided in any one of SEQ ID NOS: 364101-364110 and a corresponding third reverse primer provided in any one of SEQ ID NOS: 364111-364120, wherein the first primer pair, the second primer pair, and the third primer pair are not the same; and (d) at least three polynucleotide molecules, each polynucleotide molecule comprising a detectable moiety, wherein the polynucleotide molecule comprises a nucleic acid sequence comprising a nucleotide corresponding to nucleotide position 501 of SEQ ID NOS: 1-41, or 57-59. In some embodiments, the kit is useful for selecting a patient with an inflammatory, a fibrotic, or a fibrostenotic disease or condition for treatment with an inhibitor of TL1A activity or expression, provided the presence of the at least three polymorphisms is detected in a sample obtained from the patient.

[0057] Aspects disclosed herein provide methods of selecting a patient with an inflammatory, a fibrotic, or a fibrostenotic disease or condition for treatment with an inhibitor of TL1A activity or expression, the method comprising: (a) assaying a sample obtained from the subject using the kit of the present disclosure; (b) detecting at least three genotypes in the sample; and (c) selecting the patient for treatment with an inhibitor of TL1A activity or expression to treat an inflammatory, a fibrotic, or a fibrostenotic disease or condition in the subject. In some embodiments, methods further comprise administering the inhibitor of TL1A activity or expression to the patient to treat the inflammatory, the fibrotic, or the fibrostenotic disease or condition in the subject.

[0058] Aspects of the present disclosure provide a non-transitory computer readable medium comprising machine executable code that, upon execution by one or more computer processors, implements any of the methods above or elsewhere herein.

[0059] Aspects of the present disclosure provide a system comprising one or more computer processors and computer memory coupled thereto. The computer memory comprises machine executable code that, upon execution by the one or more computer processors, implements any of the methods above or elsewhere herein.

[0060] Aspects provided herein provide methods of treating at least one of an inflammatory, a fibrotic, and a fibrostenotic disease or condition in a subject, the method comprising administering to the subject a therapeutically effective amount of an inhibitor of TL1A activity or expression, provided a presence of a genotype is detected in a sample obtained from the subject, the genotype comprising at least three polymorphisms provided in Table 1. In some embodiments, the at least three polymorphisms is selected from the group consisting of 1511897732, rs6740739, rs17796285, 157935393, 1s12934476, 1512457255, 152070557, 154246905, 1510974900, 1512434976, 1316901748, 32815844, 1s889702, rs2409750, rs1541020, 154942248, 1512934476, 1512457255, 152297437, 1s41309367, 1s10733509, rs10750376, 1510932456, rs1326860, rs1528663, rs1892231, rs951279, rs9806914, rs7935393, rs1690492, 15420726, rs7759385, rs10974900, rs1326860, 152548147, rs2815844, rs889702, rs9806914, 156478109, 157278257, and rs11221332. In some embodiments, the at least three polymorphisms are selected from the group consisting of a “G” allele at rs11897732, an “A” allele at rs6740739, a “G” allele at rs17796285, an “A” allele at rs7935393, a “G” allele at rs12934476, an “A” allele at rs12457255, an “A” allele at rs2070557, an “A” allele at rs4246905, an “A” allele at 1810974900, a “C” allele at rs12434976, an “A” allele at rs16901748 , an “A” allele at 152815844, a “G” allele at rs889702, a “C” allele at rs2409750, an “A” allele at rs1541020, a “T” allele at rs4942248, a “G” allele at rs12934476, an “A” allele at rs12457255, an “A” allele at 152297437, a “G” allele at rs41309367, an “A” allele at 1s10733509, a “G” allele at rs10750376, a “G” allele at rs10932456, an “A” allele at rs1326860, a “G” allele at rs1528663, a “C” allele at 151892231, an “A” allele at rs951279, an “A” allele at rs9806914, an “A” allele at rs7935393, a “G” allele at rs1690492, an “A” allele at rs420726, a “T” allele at rs7759385, an “A” allele at 1810974900, an “A” allele at rs1326860, a “C” allele at rs2548147, an “A” allele at rs2815844, a “G” allele at rs889702, an “A” allele at rs9806914, an “A” allele at rs6478109, a “C” allele at 1$7278257, and an “A” allele at rs11221332. In some embodiments, a polymorphism of the at least three polymorphisms comprises a minor allele provided in Table 1. In some embodiments, a polymorphism of the at least three polymorphisms comprises a major allele provided in Table 1. In some embodiments, the genotype is heterozygous. In some embodiments, the genotype is homozygous. In some embodiments, the at least three polymorphisms comprise imm_9_116608587, imm_11_127948309, and rs1892231. In some embodiments, the at least three polymorphisms comprise imm_9_116608587, imm_11_127948309, and rs9806914. In some embodiments, the at least three polymorphisms comprise imm_9_116608587, imm_11_127948309, and imm_21_44478192. In some embodiments, the at least three polymorphisms comprise imm_9_116608587, imm_11_127948309, and imm_21_44479552. In some embodiments, the at least three polymorphisms comprise imm_9_116608587, rs1892231, and rs9806914. In some embodiments, the at least three polymorphisms comprise imm_9_ 116608587, rs1892231, and imm_21_44478192. In some embodiments, the at least three polymorphisms comprise imm_9_116608587, rs1892231, and imm_21_44479552. In some embodiments, the at least three polymorphisms comprise imm_9_116608587, rs9806914, and imm_21_44478192. In some embodiments, the at least three polymorphisms comprise imm_9_116608587, rs9806914, and imm_21_44479552. In some embodiments, the at least three polymorphisms comprise imm_9_116608587, imm_21_44478192, andimm_21_44479552. In some embodiments, the at least three polymorphisms comprise imm_11_127948309, rs1892231, and rs9806914. In some embodiments, the at least three polymorphisms comprise imm_11_127948309, rs1892231, and imm_21_44478192. In some embodiments, the at least three polymorphisms comprise imm_11_127948309, 51892231, and imm_21_44479552. In some embodiments, the at least three polymorphisms comprise imm_11_127948309, rs9806914, and imm_21_44478192. In some embodiments, the at least three polymorphisms comprise imm_11_127948309, rs9806914, and imm_21_44479552. In some embodiments, the at least three polymorphisms comprise imm_11_127948309, imm_21_44478192, and imm_21_44479552. In some embodiments, the at least three polymorphisms comprise 151892231, 159806914, and imm_21_44478192. In some embodiments, the at least three polymorphisms comprise rs1892231, rs9806914, and imm_21_44479552. In some embodiments, the at least three polymorphisms comprise rs1892231, imm_21_44478192, and imm_21_44479552. In some embodiments, the at least three polymorphisms comprise rs9806914, imm_21_44478192, and imm_21_44479552. In some embodiments, the at least three polymorphisms are detected in the sample obtained from the subject by a process of: (a) subjecting the sample obtained from the subject to an assay configured to detect at least 10 contiguous nucleic acid molecules in at least three nucleic acid sequences within SEQ ID NOS: 1-41, or 57-59, the at least 10 contiguous nucleic acid molecules comprising a risk allele at a nucleoposition 251 or 501 within SEQ ID NOS: 1-41, or 57-59; and (b) detecting the at least 10 contiguous nucleic acid molecules in the at least three nucleic acid sequences within SEQ ID NOS: 1-41, or 57-59. In some embodiments, the assay is selected from the group consisting of polymerase chain reaction (PCR), quantitative reverse-transcription PCR (qPCR), automated sequencing, genotype array, or a combination thereof. In some embodiments, the inflammatory disease or condition is selected from the group consisting of inflammatory bowel disease (IBD), Crohn’s disease (CD), obstructive CD, ulcerative colitis (UC), intestinal fibrosis, intestinal fibrostenosis, and primary sclerosing cholangitis. In some embodiments, the CD is ileal, ileocolonic, or colonic CD. In some embodiments, the subject has, or is at risk for developing, a non-response or loss-of-response to a standard therapy, the standard therapy selected from the group consisting of glucocorticosteriods, anti-TNF therapy, anti-a4-b7 therapy (vedolizumab), anti-IL12p40 therapy (ustekinumab), Thalidomide, and Cytoxan. In some embodiments, the inhibitor of TL1A is an anti-TL1A antibody or antigen-binding fragment. In some embodiments, the anti-TL1A antibody binds to the same region of human TL1A as a reference antibody, the reference antibody is selected from Table 2B. In some embodiments, the anti-TL1A antibody is a neutralizing TL1A antibody or antigen-binding fragment.

[0061] Aspects disclosed herein provide methods of selecting a subject for treatment with an inhibitor of TL1A activity or expression, the method comprising: (a) contacting a sample obtained from a subject comprising genetic material with an assay adapted to detect a presence of a genotype, the genotype comprising at least three polymorphisms provided in Table 1; and (b) selecting the subject for treatment with an inhibitor of TL1A activity or expression, provided the presence of the genotype is detected in (a). In some embodiments, methods further comprise administering or prescribing to the subject a therapeutically effective amount of the inhibitor of TL1A activity or expression. In some embodiments, methods further comprise determining whether the subject is at risk of developing a non-response or loss-of-response to a standard therapy, the standard therapy selected from the group consisting of glucocorticosteriods, anti- TNF therapy, anti-a4-b7 therapy (vedolizumab), anti-IL12p40 therapy (ustekinumab), Thalidomide, and Cytoxin. In some embodiments, the inhibitor of TL1A is an anti-TL1A antibody or antigen-binding fragment. In some embodiments, the anti-TL1A antibody binds to the same region of human TL1A as a reference antibody, the reference antibody is selected from Table 2B. In some embodiments, the anti-TL1A antibody is a neutralizing TL1A antibody or antigen-binding fragment. In some embodiments, the at least three polymorphisms is selected from the group consisting of rs11897732, rs6740739, rs17796285, 157935393, rs12934476, 1512457255, 1s2070557, 1s4246905, 1510974900, rs12434976, 1516901748, rs2815844, rs889702, 152409750, 151541020, rs4942248, 1512934476, 1812457255, 12297437, rs41309367, 1510733509, rs10750376, rs10932456, rs1326860, 151528663, rs1892231, rs951279, 1s9806914, 157935393, 151690492, rs420726, 157759385, rs10974900, rs1326860, rs2548147, rs2815844, 15889702, rs9806914, rs6478109, 17278257, and rs11221332. In some embodiments, a polymorphism of the at least three polymorphisms comprises a minor allele provided in Table 1. In some embodiments, a polymorphism of the at least three polymorphisms comprises a major allele provided in Table 1. In some embodiments, the genotype is heterozygous. In some embodiments, the genotype is homozygous. In some embodiments, the at least three polymorphisms are selected from the group consisting of a “G” allele at rs11897732, an “A” allele at rs6740739, a “G” allele at rs17796285, an “A” allele at rs7935393, a “G” allele at 1512934476, an “A” allele at rs12457255, an “A” allele at rs2070557, an “A” allele at rs4246905, an “A” allele at rs10974900, a “C” allele at rs12434976, an “A” allele at 1516901748 , an “A” allele at rs2815844, a “G” allele at rs889702, a “C” allele at rs2409750, an “A” allele at 181541020, a “T” allele at rs4942248, a “G” allele at rs12934476, an “A” allele at rs12457255, an “A” allele at rs2297437, a “G” allele at rs41309367, an “A” allele at rs10733509, a “G” allele at 1510750376, a “G” allele at rs10932456, an “A” allele at rs1326860, a “G” allele at rs1528663, a “C” allele at rs1892231, an “A” allele at rs951279, an “A” allele at 1s9806914, an “A” allele at 157935393, a “G” allele at rs1690492, an “A” allele at rs420726, a “T” allele at rs7759385, an “A” allele at rs10974900, an “A” allele at rs1326860, a “C” allele at 12548147, an “A” allele at 152815844, a “G” allele at rs889702, an “A” allele at rs9806914, an “A” allele at rs6478109, a “C” allele at rs7278257, and an “A” allele at rs11221332.In some embodiments, the at least three polymorphisms comprise imm_9_116608587, imm_11_127948309, and rs1892231. In some embodiments, the at least three polymorphisms comprise imm_9_116608587, imm_11_127948309, and rs9806914. In some embodiments, the at least three polymorphisms comprise imm_9_116608587, imm_11_127948309, and imm_21_44478192. In some embodiments, the at least three polymorphisms comprise imm_9_116608587, imm_11_127948309, and imm_21_44479552. In some embodiments, the at least three polymorphisms comprise imm_9_116608587, rs1892231, and rs9806914. In some embodiments, the at least three polymorphisms comprise imm_9_116608587, rs1892231, and imm_21_44478192. In some embodiments, the at least three polymorphisms comprise imm_9_116608587, rs1892231, and imm_21_44479552. In some embodiments, the at least three polymorphisms comprise imm_9_116608587, rs9806914, and imm_21_44478192. In some embodiments, the at least three polymorphisms comprise imm_9_116608587, rs9806914, and imm_21_44479552. In some embodiments, the at least three polymorphisms comprise imm_9_ 116608587, imm_21_44478192, andimm_21_44479552. In some embodiments, the at least three polymorphisms comprise imm_11_127948309, rs1892231, and rs9806914. In some embodiments, the at least three polymorphisms comprise imm_11_127948309, rs1892231, and imm_21_44478192. In some embodiments, the at least three polymorphisms comprise imm_11_127948309, rs1892231, and imm_21_44479552. In some embodiments, the at least three polymorphisms comprise imm_11_127948309, rs9806914, and imm_21_44478192. In some embodiments, the at least three polymorphisms comprise imm_11_127948309, rs9806914, and imm_21_44479552. In some embodiments, the at least three polymorphisms comprise imm_11_127948309, imm_21_44478192, and imm_21_44479552. In some embodiments, the at least three polymorphisms comprise rs1892231, rs9806914, and imm_21_44478192. In some embodiments, the at least three polymorphisms comprise rs1892231, rs9806914, and imm_21_44479552. In some embodiments, the at least three polymorphisms comprise 1s1892231, imm_21_44478192, and imm_21_44479552. In some embodiments, the at least three polymorphisms comprise rs9806914, imm_21_44478192, and imm_21_44479552.

[0062] Aspects disclosed herein provide methods of treating at least one of an inflammatory, a fibrotic, and a fibrostenotic disease or condition in a subject, the method comprising: (a) determining whether a subject is, or is at risk for developing, non-response or loss-of-response to a standard therapy; (b) determining whether the subject is suitable for treatment with an inhibitor of TL1A activity or expression by a process of’ (i) contacting a sample obtained from the subject with an assay adapted to detect a presence of a genotype, the genotype comprising at least three polymorphisms selected from Table 1; and (ii) detecting the genotype in the sample obtained from the subject; and (c) if the subject is not determined to have, or be at risk for developing, the non-response or loss-of-response to the standard therapy, then treating the subject by administering a therapeutically effective amount of the standard therapy to the subject; and (d) if the subject is determined to have, or be at risk for developing, the non-response or loss-of- response to the standard therapy, and the subject is determined to be suitable for treatment with the inhibitor of TL1A activity or expression, then treating the subject by administering a therapeutically effective amount of the inhibitor of TL1A activity or expression to the subject. In some embodiments, the at least three polymorphisms is selected from the group consisting of 1511897732, rs6740739, rs17796285, rs7935393, 1512934476, 1512457255, rs2070557, 154246905, rs10974900, 1512434976, rs16901748, 152815844, 15889702, rs2409750, rs1541020, 154942248, 1512934476, 1512457255, rs2297437, rs41309367, 1510733509, rs10750376, 1510932456, 131326860, 151528663, 1s1892231, 15951279, rs9806914, rs7935393, rs1690492, 15420726, 1s7759385, rs10974900, rs1326860, 152548147, rs2815844, rs889702, rs9806914, 156478109, 157278257, and rs11221332. In some embodiments, a polymorphism of the at least three polymorphisms comprises a minor allele provided in Table 1. In some embodiments, a polymorphism of the at least three polymorphisms comprises a major allele provided in Table 1. In some embodiments, the genotype is heterozygous. In some embodiments, the genotype is homozygous. In some embodiments, the at least three polymorphisms are selected from the group consisting of a “G” allele at rs11897732, an “A” allele at rs6740739, a “G” allele at 1817796285, an “A” allele at rs7935393, a “G” allele at rs12934476, an “A” allele at rs12457255, an “A” allele at rs2070557, an “A” allele at rs4246905, an “A” allele at rs10974900, a “C” allele at 1s12434976, an “A” allele at rs16901748 , an “A” allele at rs2815844, a “G” allele at 15889702, a “C” allele at rs2409750, an “A” allele at rs1541020, a “T” allele at rs4942248, a “G” allele at rs12934476, an “A” allele at 1512457255, an “A” allele at rs2297437, a “G” allele at 1541309367, an “A” allele at rs10733509, a “G” allele at rs10750376, a “G” allele at rs10932456, an “A” allele at rs1326860, a “G” allele at rs1528663, a “C” allele at rs1892231, an “A” allele at 18951279, an “A” allele at rs9806914, an “A” allele at rs7935393, a “G” allele at rs1690492, an “A” allele at rs420726, a “T” allele at rs7759385, an “A” allele at rs10974900, an “A” allele at 151326860, a “C” allele at rs2548147, an “A” allele at rs2815844, a “G” allele at rs889702, an “A” allele at rs9806914, an “A” allele at rs6478109, a “C” allele at rs7278257, and an “A” allele at rs11221332. In some embodiments, the at least three polymorphisms comprise imm_9_116608587, imm_11_127948309, and rs1892231. In some embodiments, the at least three polymorphisms comprise imm_9_116608587, imm_11_127948309, and rs9806914. In some embodiments, the at least three polymorphisms comprise imm_9_116608587, imm_11_127948309, and imm_21_44478192. In some embodiments, the at least three polymorphisms comprise imm_9_116608587, imm_11_127948309, and imm_21_44479552. In some embodiments, the at least three polymorphisms comprise imm_9_116608587, rs1892231, and rs9806914. In some embodiments, the at least three polymorphisms comprise imm_9_116608587, rs1892231, and imm_21_44478192. In some embodiments, the at least three polymorphisms comprise imm_9_116608587, rs1892231, and imm_21_44479552. In some embodiments, the at least three polymorphisms comprise imm_9_116608587, rs9806914, and imm_21_44478192. In some embodiments, the at least three polymorphisms comprise imm_9_116608587, rs9806914, and imm_21_44479552. In some embodiments, the at least three polymorphisms comprise imm_9_116608587, imm_21_44478192, andimm_21_44479552. In some embodiments, the at least three polymorphisms comprise imm_11_127948309, rs1892231, and rs9806914. In some embodiments, the at least three polymorphisms comprise imm_11_127948309, rs1892231, and imm_21_44478192. In some embodiments, the at least three polymorphisms comprise imm_11_127948309, rs1892231, and imm_21_44479552. In some embodiments, the at least three polymorphisms comprise imm_11_127948309, rs9806914, and imm_21_44478192. In some embodiments, the at least three polymorphisms comprise imm_11_127948309, 19806914, and imm_21_44479552, In some embodiments, the at least three polymorphisms comprise imm_11_127948309, imm_21_44478192, and imm_21_44479552. In some embodiments, the at least three polymorphisms comprise 151892231, 159806914, and imm_21_44478192. In some embodiments, the at least three polymorphisms comprise rs1892231, rs9806914, and imm_21_44479552. In some embodiments, the at least three polymorphisms comprise rs1892231, imm_21_44478192, and imm_21_44479552. In some embodiments, the at least three polymorphisms comprise 159806914, imm_21_44478192, and imm_21_44479552. In some embodiments, the standard therapy is selected from the group consisting of glucocorticosteriods, anti-TNF therapy, anti-a4- b7 therapy (vedolizumab), anti-IL12p40 therapy (ustekinumab), Thalidomide, and Cytoxin.

[0063] Additional aspects and advantages of the present disclosure will become readily apparent to those skilled in this art from the following detailed description, wherein only illustrative embodiments of the present disclosure are shown and described. As will be realized, the present disclosure is capable of other and different embodiments, and its several details are capable of modifications in various obvious respects, all without departing from the disclosure. Accordingly, the drawings and description are to be regarded as illustrative in nature, and not as restrictive INCORPORATION BY REFERENCE

[0064] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. To the extent publications and patents or patent applications incorporated by reference contradict the disclosure contained in the specification, the specification is intended to supersede and / or take precedence over any such contradictory material. BRIEF DESCRIPTION OF THE DRAWINGS

[0065] The novel features of the inventive concepts set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings (also “Figure” and “FIG.” herein), of which:

[0066] FIG. 1 shows a workflow according to an embodiment of the present disclosure for processing a biological sample obtained from a subject to inform the selection of a therapeutic agent to treat a disease or a condition of the subject.

[0067] FIG. 2 shows a computer-implemented workflow according to an embodiment of the present disclosure for generating an electronic report to a user, such as a physician, comprising a TNFSF15 profile of a subject based on an analysis of genotype data from the subject.

[0068] FIG. 3 shows a computer system that is programmed or otherwise configured to implement methods provided herein.

[0069] FIG. 4 shows a computer-implemented workflow according to an embodiment of the present disclosure for producing a TNFSF15 profile.

[0070] FIG. 5A-5C shows a clustering analysis within our the TL1A companion diagnostic (CDx) dataset, FIG. 5A shows cluster 1, FIG. 5B shows cluster 2, and FIG. 5C shows cluster 3, from the TL1A CDx dataset.

[0071] FIG. 6 shows that the 3 clusters from FIG. SA-5C were collapsed into 2 clusters (high TL1A expression clusters shown on the left) and (low TL1A expression clusters on the right). DETAILED DESCRIPTION

[0072] Provided herein are methods, systems, and kits for identifying a subject who may be suitable for treatment with an inhibitor of Tumor Necrosis Factor (Ligand) Superfamily, Member 15 (TL1A) activity or expression, provided the subject is a carrier of a genotype. The subject may be a patient, who may be diagnosed with an inflammatory disease, a fibrostenotic disease, or a fibrotic disease, such as inflammatory bowel disease (IBD) or Crohn’s disease (CD). The subject may not be a patient, but may be suspected of having the inflammatory disease, the fibrostenotic disease, or the fibrotic disease. The genotype may, in some cases, be useful for characterizing the inflammatory fibrostenotic, or fibrotic disease or condition, as mediated by TL1A. The subject, in some embodiments, is treated by administering the inhibitor of TL1A activity or expression (e.g., anti-TL1A antibody) to the subject, provided the genotype is detected. In some cases, identifying the subject as being suitable for treatment with the inhibitor of activity or expression is required in order to administer the inhibitor to the subject.

[0073] Referring to FIG. 1, the methods, systems and kits of the present disclosure involve, in some embodiments, the steps of providing a buccal swab sample from a subject 101, optionally purifying DNA from the sample by processing the sample 102, assaying the optionally processed sample to detect genotypes of at least three genetic loci in the sample 103, processing the genotypes to produce a TNFSF15 profile 104, and selecting a therapy to treat a disease or disorder of the subject based on the TNFSF15 profile 105.

[0074] The genotypes described herein are detected using suitable genotyping devices (e.g., array, sequencing). In some instances, a sample is obtained from the subject or patient indirectly or directly. In some instances, the sample may be obtained by the subject. In other instances, the sample may be obtained by a healthcare professional, such as a nurse or physician. The sample may be derived from virtually any biological fluid or tissue containing genetic information, such as blood.

[0075] The subject disclosed herein can be a mammal, such as for example a mouse, rat, guinea pig, rabbit, non-human primate, or farm animal. In some instances, the subject is human. In some instances, the subject is suffering from a symptom related to a disease or condition disclosed herein (e.g., abdominal pain, cramping, diarrhea, rectal bleeding, fever, weight loss, fatigue, loss of appetite, dehydration, and malnutrition, anemia, or ulcers).

[0076] In some embodiments, the subject is susceptible to, or is inflicted with, thiopurine toxicity, or a disease caused by thiopurine toxicity (such as pancreatitis or leukopenia). The subject may experience, or is suspected of experiencing, non-response or loss-of-response to a standard treatment (e.g., anti-TNF alpha therapy, anti-a4-b7 therapy (vedolizumab), anti-IL12p40 therapy (ustekinumab), Thalidomide, or Cytoxin).

[0077] The disease or condition disclosed herein may be an inflammatory disease, a fibrostenotic disease, or a fibrotic disease. In some instances, the disease or the condition is a TL1A-mediated disease or condition. The term, “TL1A-mediated disease or condition” refers to a disease or a condition pathology or pathogenesis that is driven, at least in part, by TL1A signaling. In some instances, the disease or the condition is immune-mediated disease or condition, such as those mediated by TL1A.

[0078] In some embodiments the disease or the condition is an inflammatory disease or disorder that is mediated, at least in part, by TL1A signaling. Non-limiting examples of inflammatory disease include, allergy, ankylosing spondylitis, asthma, atopic dermatitis, autoimmune diseases or disorders, cancer, celiac disease, chronic obstructive pulmonary disease (COPD), chronic peptic ulcer, cystic fibrosis, diabetes (e.g, type 1 diabetes and type 2 diabetes), glomerulonephritis, gout, hepatitis (e.g., active hepatitis), an immune-mediated disease or disorder, inflammatory bowel disease (IBD) such as Crohn’s disease and ulcerative colitis, myositis, osteoarthritis, pelvic inflammatory disease (PID), multiple sclerosis, neurodegenerative diseases of aging, periodontal disease (e.g., periodontitis), preperfusion injury transplant rejection, psoriasis, pulmonary fibrosis, rheumatic disease, scleroderma, sinusitis, tuberculosis.

[0079] In some embodiments, the disease or the condition is an autoimmune disease that is mediated, at least in part, by TL1A signaling. Non-limiting examples of autoimmune disease or disorder include Achalasia, Addison’s disease, Adult Still's disease, Agammaglobulinemia, Alopecia areata, Amyloidosis, Ankylosing spondylitis, Anti-GBM / Anti-TBM nephritis, Antiphospholipid syndrome, Autoimmune angioedema, Autoimmune dysautonomia, Autoimmune encephalomyelitis, Autoimmune hepatitis, Autoimmune inner ear disease (AIED), Autoimmune myocarditis, Autoimmune oophoritis, Autoimmune orchitis, Autoimmune pancreatitis, Autoimmune retinopathy, Autoimmune urticaria, Axonal & neuronal neuropathy (AMAN), Bal¢ disease, Behcet's disease, Benign mucosal pemphigoid, Bullous pemphigoid, Castleman disease (CD), Celiac disease, Chagas disease, Chronic inflammatory demyelinating polyneuropathy (CIDP), Chronic recurrent multifocal osteomyelitis (CRMO), Churg-Strauss Syndrome (CSS) or Eosinophilic Granulomatosis (EGPA), Cicatricial pemphigoid, Cogan’s syndrome, Cold agglutinin disease, Congenital heart block, Coxsackie myocarditis, CREST syndrome, Crohn’s disease, Dermatitis herpetiformis, Dermatomyositis, Devic’s disease (neuromyelitis optica), Discoid lupus, Dressler’s syndrome, Endometriosis, Eosinophilic esophagitis (EoE), Eosinophilic fasciitis, Erythema nodosum, Essential mixed cryoglobulinemia, Evans syndrome, Fibromyalgia, Fibrosing alveolitis, Giant cell arteritis (temporal arteritis), Giant cell myocarditis, Glomerulonephritis, Goodpasture’s syndrome, Granulomatosis with Polyangiitis, Graves’ disease, Guillain-Barre syndrome, Hashimoto's thyroiditis, Hemolytic anemia, Henoch-Schonlein purpura (HSP), Herpes gestationis or pemphigoid gestationis (PG), Hidradenitis Suppurativa (HS) (Acne Inversa), Hypogammalglobulinemia, IgA Nephropathy, IgG4-related sclerosing disease, Immune thrombocytopenic purpura (ITP), Inclusion body myositis (IBM), Interstitial cystitis (IC), Juvenile arthritis, Juvenile diabetes (Type 1 diabetes), Juvenile myositis (JM), Kawasaki disease, Lambert-Eaton syndrome, Leukocytoclastic vasculitis, Lichen planus, Lichen sclerosus, Ligneous conjunctivitis, Linear IgA disease (LAD), Lupus, Lyme disease chronic, Meniere's disease, Microscopic polyangiitis (MPA), Mixed connective tissue disease (MCTD), Mooren’s ulcer, Mucha-Habermann disease, Multifocal Motor Neuropathy (MMN) or MMNCB, Multiple sclerosis, Myasthenia gravis, Myositis, Narcolepsy, Neonatal Lupus, Neuromyelitis optica, Neutropenia, Ocular cicatricial pemphigoid, Optic neuritis, Palindromic rheumatism (PR), PANDAS, Paraneoplastic cerebellar degeneration (PCD), Paroxysmal nocturnal hemoglobinuria (PNH), Parry Romberg syndrome, Pars planitis (peripheral uveitis), Parsonage-Turner syndrome, Pemphigus, Peripheral neuropathy, Perivenous encephalomyelitis, Pernicious anemia (PA), POEMS syndrome, Polyarteritis nodosa, Polyglandular syndromes type I, II, III, Polymyalgia rheumatica, Polymyositis, Postmyocardial infarction syndrome, Postpericardiotomy syndrome, Primary biliary cirrhosis, Primary sclerosing cholangitis, Progesterone dermatitis, Psoriasis, Psoriatic arthritis, Pure red cell aplasia (PRCA), Pyoderma gangrenosum, Raynaud’s phenomenon, Reactive Arthritis, Reflex sympathetic dystrophy, Relapsing polychondritis, Restless legs syndrome (RLS), Retroperitoneal fibrosis, Rheumatic fever, Rheumatoid arthritis, Sarcoidosis, Schmidt syndrome, Scleritis, Scleroderma, Sjogren’s syndrome, Sperm & testicular autoimmunity, Stiff person syndrome (SPS), Subacute bacterial endocarditis (SBE), Susac’s syndrome, Sympathetic ophthalmia (SO), Takayasu's arteritis, Temporal arteritis / Giant cell arteritis, Thrombocytopenic purpura (TTP), Tolosa-Hunt syndrome (THS), Transverse myelitis, Type 1 diabetes, Ulcerative colitis (UC), Undifferentiated connective tissue disease (UCTD), Uveitis, Vasculitis, Vitiligo, and Vogt-Koyanagi-Harada Disease.

[0080] In some embodiments, the disease or the condition is a cancer that is mediated, at least in part, by TL1A signaling. Non-limiting examples of cancers include Adenoid Cystic Carcinoma, Adrenal Gland Cancer, Amyloidosis, Anal Cancer, Ataxia-Telangiectasia, Atypical Mole Syndrome, Basal Cell Carcinoma, Bile Duct Cancer, Birt Hogg Dube Syndrome, Bladder Cancer, Bone Cancer, Brain Tumor, Breast Cancer, Breast Cancer in Men, Carcinoid Tumor, Cervical Cancer, Colorectal Cancer, Ductal Carcinoma, Endometrial Cancer, Esophageal Cancer, Gastric Cancer, Gastrointestinal Stromal Tumor (GIST), HER2-Positive Breast Cancer, Islet Cell Tumor, Juvenile Polyposis Syndrome, Kidney Cancer, Laryngeal Cancer, Leukemia - Acute Lymphoblastic Leukemia, Leukemia - Acute Lymphocytic (ALL), Leukemia - Acute Myeloid AML, Leukemia - Adult, Leukemia - Childhood, Leukemia - Chronic Lymphocytic (CLL), Leukemia - Chronic Myeloid (CML), Liver Cancer, Lobular Carcinoma, Lung Cancer, Lung Cancer - Small Cell (SCLC), Lung Cancer - Non-small Cell (NSCLC), Lymphoma - Hodgkin's, Lymphoma - Non-Hodgkin's, Malignant Glioma, Melanoma, Meningioma, Multiple Myeloma, Myelodysplastic Syndrome (MDS), Nasopharyngeal Cancer, Neuroendocrine Tumor, Oral Cancer, Osteosarcoma, Ovarian Cancer, Pancreatic Cancer, Pancreatic Neuroendocrine Tumors, Parathyroid Cancer, Penile Cancer, Peritoneal Cancer, Peutz-Jeghers Syndrome, Pituitary Gland Tumor, Polycythemia Vera, Prostate Cancer, Renal Cell Carcinoma, Retinoblastoma, Salivary Gland Cancer, Sarcoma, Sarcoma - Kaposi, Skin Cancer, Small Intestine Cancer, Stomach Cancer, Testicular Cancer, Thymoma, Thyroid Cancer, Uterine (Endometrial) Cancer, Vaginal Cancer, and Wilms’ Tumor.

[0081] In some embodiments, the disease or the condition is an inflammatory bowel disease, such as Crohn’s disease (CD) or ulcerative colitis (UC). A subject may suffer from fibrosis, fibrostenosis, or a fibrotic disease, either isolated or in combination with an inflammatory disease. In some cases, the CD is severe CD. The severe CD may result from inflammation that has led to the formation of scar tissue in the intestinal wall (fibrostenosis) and / or swelling. In some cases, the severe CD is characterized by the presence of fibrotic and / or inflammatory strictures. The strictures may be determined by computed tomography enterography (CTE), and magnetic resonance imaging enterography (MRE). The disease or condition may be characterized as refractory, which in some cases, means the disease is resistant to a standard treatment (e.g., anti-TNFa therapy). Non-limiting examples of standard treatment include glucocorticosteriods, anti-TNF therapy, anti-a4-b7 therapy (vedolizumab), anti-IL12p40 therapy (ustekinumab), Thalidomide, and Cytoxin. GENOTYPES

[0082] Disclosed herein are genotypes that may be detected in a sample obtained from a subject by analyzing the genetic material in the sample. In some instances, the subject may be human. In some embodiments, the genetic material is obtained from a subject having a disease or condition disclosed herein. In some cases, the genetic material is obtained from blood, serum, plasma, sweat, hair, tears, urine, and other techniques known by one of skill in the art. In some cases, the genetic material is obtained from a biopsy, e.g., from the intestinal track of the subject.

[0083] The genotypes of the present disclosure comprise genetic material that is deoxyribonucleic acid (DNA). In some instances, the genotype comprises a denatured DNA molecule or fragment thereof. In some instances, the genotype comprises DNA selected from: genomic DNA, viral DNA, mitochondrial DNA, plasmid DNA, amplified DNA, circular DNA, circulating DNA, cell-free DNA, or exosomal DNA. In some instances, the DNA is single- stranded DNA (ssDNA), double-stranded DNA, denaturing double-stranded DNA, synthetic DNA, and combinations thereof. The circular DNA may be cleaved or fragmented.

[0084] The genotypes disclosed herein comprise at least one polymorphism at a gene or genetic locus described herein. In some instances, the gene or genetic locus is selected from the group consisting of Tumor Necrosis Factor (Ligand) Superfamily, Member 15 (TNFSF15), THADA Armadillo Repeat Containing (THADA), Pleckstrin Homology, MyTH4 And FERM Domain Containing H2 (PLEKHH2), XK Related 6 (XKR6), Myotubularin Related Protein 9 (MTMRO9), ETS Proto-Oncogene 1, Transcription Factor (ETS1), C-Type Lectin Domain Containing 16A (CLEC16A), Suppressor Of Cytokine Signaling 1 (SOCS1), Protein Tyrosine Phosphatase Non-Receptor Type 2 (PTPN2), Inducible T Cell Costimulator Ligand (ICOSLG), Janus Kinase 2 (JAK2), Catenin Delta 2 (CTNND2), Regulator Of G Protein Signaling 7 (RGS7), RNA Binding Fox-1 Homolog 1 (RBFOX1), RNA Binding Motif Protein 17 (RBM17), 6-Phosphofructo-2-Kinase / Fructose-2,6-Biphosphatase 3 (PFKFB3), Ecto-NOX Disulfide-Thiol Exchanger 1 (ENOX1), Coiled-Coil Domain Containing 122 (CCDC122), Regulator Of Telomere Elongation Helicase 1 (RTEL1), TNF Receptor Superfamily Member 6b (TNFRSF6B), GLIS Family Zinc Finger 3 (GLIS3), Solute Carrier Family 1 Member 1 (SLC1A1), IKAROS Family Zinc Finger 2 (IKZF2), Fatty Acyl-CoA Reductase 1 (FAR1), Spondin 1(SPONT1), Plexin A2 (PLXNA2), MIR205 Host Gene (MIR205HG), C-Type Lectin Domain Containing 16A (CLEC16A), PR / SET Domain 14 (PRDM), Autophagy Related 5 (ATGS), and Prostaglandin E Receptor 4 (PTGER4). In some instances, the gene or genetic locus comprises a gene or genetic locus provided in Table 1. The genotypes disclosed herein are, in some cases, a haplotype. In some instances, the genotype comprises a particular polymorphism, a polymorphism in linkage disequilibrium (LD) therewith, or a combination thereof. In some cases, LD is defined by an r? of at least or about 0.70, 0.75, 0.80, 0.85, 0.90, or 1.0. The genotypes disclosed herein can comprise at least or about 1,2, 3, 4, 5,6, 7, 8,9, 10, 11, 12,13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, or more polymorphisms. In preferred embodiments, the genotypes disclosed herein comprise a combination of 3 polymorphisms, such as those provided in Table 1.

[0085] The polymorphisms described herein can be a single nucleotide polymorphism, or an indel (insertion / deletion). In some instances, the polymorphism is an insertion or a deletion of at least one nucleobase (e.g., an indel). In some instances, the genotype may comprise a copy number variation (CNV), which is a variation in a number of a nucleic acid sequence between individuals in a given population. In some instances, the CNV comprises at least or about two, three, four, five, six, seven, eight, nine, ten, twenty, thirty, forty or fifty nucleic acid molecules. In some instances, the genotype is heterozygous. In some instances, the genotype is homozygous.

[0086] Disclosed herein, in the following embodiments, are genotypes disclosed herein: Lk A genotype comprising at least one polymorphism at a gene or genetic locus. 2 The genotype of embodiment 1 comprising a polymorphism provided in Table 1. 3. The genotype of embodiments 1-2 that is heterozygous. 4, The genotype of embodiments 1-2 that is homozygous. 5. The genotype of embodiments 1-4, wherein the genotype comprises at least two polymorphisms. 6. The genotype of embodiments 1-4, wherein the genotype comprises at least three polymorphisms. 7, The genotype of embodiments 1-4, wherein the genotype comprises at least four polymorphisms. 8. The genotype of embodiment 1, comprising a polymorphism in linkage disequilibrium with a polymorphism provided in Table 1. 9. The genotype of embodiment 8, wherein LD is defined by (i) a D’ value of at least about 0.70, or (ii) a D’ value of 0 and an r* value of at least about 0.70. 10. The genotype of embodiment 8, whe'ein LD is defined by (i) a D’ value of at least about 0.80, or (ii) a D’ value of 0 and an r? value of at least about 0.80. 11. The genotype of embodiment 8, wherein LD is defined by (i) a D’ value of at least about 0.90, or (ii) a D’ value of 0 and an r? value of at least about 0.90. 12. The genotype of embodiment 8, wherein LD is defined by (i) a D’ value of at least about 0.95, or (ii) a D’ value of 0 and an r* value of at least about 0.95. 13. The genotype of embodiments 1-12, wherein the gene or genetic locus is selected from the group consisting of Tumor Necrosis Factor (Ligand) Superfamily, Member 15 (TNFSF15), THADA Armadillo Repeat Containing (THADA), Pleckstrin Homology, MyTH4 And FERM Domain Containing H2 (PLEKHH2), XK Related 6 (XKR6), Myotubularin Related Protein 9 (MTMR9), ETS Proto-Oncogene 1, Transcription Factor (ETS1), C-Type Lectin Domain Containing 16A (CLEC16A), Suppressor Of Cytokine Signaling 1 (SOCS1), Protein Tyrosine Phosphatase Non-Receptor Type 2 (PTPN2), Inducible T Cell Costimulator Ligand (ICOSLG), Janus Kinase 2 (JAK2), Catenin Delta 2 (CTNND2), Regulator Of G Protein Signaling 7 (RGS7), RNA Binding Fox-1 Homolog 1 (RBFOX1), RNA Binding Motif Protein 17 (RBM17), 6-Phosphofructo-2- Kinase / Fructose-2,6-Biphosphatase 3 (PFKFB3), Ecto-NOX Disulfide-Thiol Exchanger 1 (ENOX1), Coiled-Coil Domain Containing 122 (CCDC122), Regulator Of Telomere Elongation Helicase 1 (RTEL1), TNF Receptor Superfamily Member 6b (TNFRSF6B), GLIS Family Zinc Finger 3 (GLIS3), Solute Carrier Family 1 Member 1 (SLC1ALl), IKAROS Family Zinc Finger 2 (IKZF2), Fatty Acyl-CoA Reductase 1 (FAR1), Spondin 1(SPONT1), Plexin A2 (PLXNA2), MIR205 Host Gene (MIR205SHG), C-Type Lectin Domain Containing 16A (CLEC16A), PR / SET Domain 14 (PRDM), Autophagy Related 5 (ATGS), and Prostaglandin E Receptor 4 (PTGER4). The genotype of embodiments 5-6, wherein the genotype comprises at least two polymorphisms selected from: (1) 1516901748, rs7759385, rs4246905; (2) 1516901748, rs7759385, rs7935393; 3) 1516901748, rs7759385, rs1892231; 4) 1516901748, rs7759385, 1512934476; (5) 1rs16901748, rs7759385, rs9806914; (6) 1rs16901748, rs7759385, rs2297437; (7) 1rs16901748, rs7759385, rs2070557; (8) rs16901748, rs7759385, rs7278257; (9) 1516901748, rs7759385, 1511221332; (10) rs16901748, rs7759385, rs41309367; (11) 1rs16901748, rs7759385, rs6478109; (12) 1rs16901748, rs4246905, rs7935393; (13) 1rs16901748, rs4246905, rs1892231; (14) 1516901748, rs4246905, rs12934476; (15) 1s16901748, rs4246905, rs9806914; (16) 1516901748, rs4246905, rs2297437; (17) 1rs16901748, rs4246905, rs2070557; (18) 1rs16901748, rs4246905, rs7278257; 1516901748, rs4246905, 1311221332; 1516901748, rs4246905, 1541309367, 1516901748, rs4246905, rs6478109; 1516901748, rs7935393, 1s1892231, 1516901748, rs7935393, 1312934476; 1516901748, rs7935393, 159806914; 1516901748, rs7935393, 152297437; 1516901748, rs7935393, 152070557; 1516901748, rs7935393, 187278257, 1516901748, rs7935393, 1511221332; 1516901748, rs7935393, 141309367, 1516901748, rs7935393, 16478109, 1516901748, rs1892231, 1512934476; 1516901748, rs1892231, 159806914; 1516901748, rs1892231, 152297437; 1516901748, rs1892231, 152070557; 1516901748, rs1892231, 187278257, 1516901748, rs1892231, 1s11221332; 1516901748, rs1892231, rs41309367, 1516901748, rs1892231, rs6478109; 1516901748, rs12934476, rs9806914; 1516901748, rs12934476, 152297437; 1516901748, rs12934476, rs2070557; 1516901748, rs12934476, 157278257; 1516901748, rs12934476, 511221332; 1516901748, rs12934476, rs41309367; 1516901748, rs12934476, rs6478109, 1516901748, rs9806914, 152297437, 1516901748, rs9806914, 152070557; 1516901748, rs9806914, 157278257; 1516901748, rs9806914, 1511221332; 1516901748, rs9806914, 1541309367; 1516901748, rs9806914, rs6478109; 1516901748, rs2297437, rs2070557; 1516901748, rs2297437, 187278257, 1516901748, rs2297437, 1311221332; 1516901748, rs2297437, 1541309367, 1516901748, rs2297437, 1s6478109, 1516901748, rs2070557, 157278257; 1516901748, rs2070557, 111221332; 1516901748, rs2070557, 141309367; 1516901748, rs2070557, 156478109; 1516901748, rs7278257, 111221332; 1516901748, rs7278257, 1s41309367, 1516901748, rs7278257, 1s6478109, 1516901748, rs11221332, rs41309367; 1516901748, rs11221332, rs6478109; 1516901748, rs41309367, rs6478109; 157759385, 154246905, 17935393; 157759385, 154246905, 151892231; 157759385, 1542469085, 1512934476, 157759385, 1542469085, 159806914; 187759385, 1542469085, 152297437, 187759385, 1542469085, 12070557, 157759385, 154246905, 157278257, 157759385, 154246905, 1511221332; 157759385, 154246905, 1541309367; 157759385, 154246905, 156478109; 187759385, 157935393, 151892231; 157759385, 157935393, 1512934476, 187759385, 157935393, 159806914; 187759385, 157935393, 152297437, 157759385, 157935393, 152070557, 157759385, 157935393, 157278257, 157759385, 157935393, 1511221332; 157759385, 157935393, 1541309367; 187759385, 157935393, 156478109; 157759385, rs1892231, 1512934476; 187759385, 151892231, 159806914; 187759385, 11892231, 152297437, 187759385, rs1892231, 152070557, 187759385, rs1892231, 157278257, 157759385, 151892231, 1511221332; 157759385, 151892231, 1541309367; 157759385, 151892231, 156478109; 157759385, 1512934476, 159806914; 187759385, 1512934476, 132297437, 187759385, 1512934476, 12070557, 157759385, 1512934476, 17278257, 157759385, 1512934476, 1311221332; 157759385, 1512934476, 1541309367; 157759385, 1512934476, 156478109; 157759385, 159806914, 152297437, 157759385, 159806914, 152070557, 157759385, rs9806914, 157278257, 157759385, rs9806914, 1511221332; 157759385, 159806914, 1541309367, 187759385, 159806914, 156478109; 157759385, 152297437, 152070557, 157759385, 152297437, 157278257, 157759385, 152297437, 1511221332; 157759385, 152297437, 1541309367; 187759385, 152297437, 156478109; 187759385, 152070557, 17278257, 187759385, 152070557, rs11221332, 187759385, 152070557, 1541309367, 157759385, 152070557, 156478109; 157759385, 157278257, 1511221332; 157759385, 157278257, 1541309367; 157759385, 157278257, 156478109; 187759385, rs11221332, 1341309367, 157759385, rs11221332, rs6478109; 187759385, 1541309367, 16478109, 184246905, 157935393, 151892231; 154246905, 157935393, 1512934476, 154246905, 157935393, 159806914; 154246905, 157935393, 152297437, 154246905, 157935393, 152070557, 154246905, 157935393, 157278257, 154246905, 157935393, 1511221332; 154246905, 157935393, 1541309367, 154246905, 157935393, 156478109; 154246905, 151892231, 1512934476, 154246905, 151892231, 159806914; 154246905, 151892231, 152297437, 154246905, 151892231, 152070557, 154246905, 151892231, 157278257, 154246905, 151892231, 1511221332; 154246905, 151892231, 1541309367, 154246905, 11892231, 156478109; 154246905, 1512934476, 1s9806914, 154246905, 1512934476, 132297437, 154246905, 1512934476, 152070557; 154246905, 1512934476, 157278257; 154246905, 1512934476, 1311221332; 154246905, 1512934476, 1541309367; 154246905, 1512934476, 156478109; 154246905, rs9806914, 152297437, 154246905, rs9806914, 152070557, 154246905, rs9806914, 157278257, 154246905, 159806914, 1511221332; 154246905, 159806914, 1541309367; 154246905, 159806914, 156478109; 154246905, 152297437, 152070557, 154246905, 152297437, 17278257, 154246905, 152297437, 1511221332; 154246905, 152297437, 1541309367, 184246905, 152297437, 156478109; 154246905, 152070557, 17278257, 154246905, 152070557, rs11221332, 154246905, 152070557, 1541309367; 154246905, 152070557, 156478109; 154246905, 157278257, 1511221332; 154246905, 157278257, 1541309367; 154246905, 157278257, 156478109; 154246905, rs11221332, 141309367, 154246905, 1511221332, 16478109, 154246905, 1541309367, 156478109, 157935393, 151892231, 1512934476; 157935393, 151892231, 159806914; 157935393, 151892231, 152297437, 157935393, 151892231, 152070557, 157935393, rs1892231, 157278257, 157935393, rs1892231, 511221332; 157935393, rs1892231, 1541309367, 187935393, rs1892231, 156478109; 157935393, 1512934476, 159806914; 157935393, 1512934476, 152297437; 157935393, 1512934476, 152070557; 157935393, 1512934476, 157278257; 187935393, 1512934476, 1311221332; 157935393, 1512934476, 1541309367, 157935393, 1512934476, 156478109, 187935393, rs9806914, 152297437, 157935393, 159806914, 152070557, 157935393, 159806914, 157278257, 157935393, 159806914, 1511221332; 157935393, 159806914, 1541309367; 187935393, rs9806914, 156478109; 157935393, 152297437, 152070557; 187935393, 152297437, 137278257, 187935393, 152297437, 1511221332; 157935393, 152297437, 1541309367, 187935393, 152297437, 1356478109; 157935393, rs2070557, 137278257, 157935393, rs2070557, 1311221332; 157935393, rs2070557, rs41309367; 157935393, rs2070557, rs6478109; 187935393, 157278257, 1511221332, 187935393, 157278257, 1541309367, 187935393, 157278257, 156478109; 157935393, rs11221332, 134130936;7 157935393, rs11221332, 156478109; 157935393, rs41309367, 156478109; 151892231, rs12934476, 159806914; 151892231, rs12934476, 152297437; 151892231, 1512934476, 12070557, 151892231, rs12934476, 17278257, 151892231, rs12934476, 1311221332; 181892231, rs12934476, 1s41309367, 151892231, rs12934476, 156478109; 151892231, rs9806914, rs2297437,; 151892231, rs9806914, rs2070557,; 151892231, 159806914, rs7278257, 151892231, rs9806914, 1511221332; 151892231, rs9806914, 1541309367, 151892231, rs9806914, 156478109; 181892231, 152297437, 152070557, 151892231, rs2297437, 137278257, 1s1892231, rs2297437, 1311221332; 151892231, rs2297437, rs41309367; 151892231, 152297437, rs6478109; 181892231, rs2070557, 17278257, 151892231, rs2070557, rs11221332; 181892231, rs2070557, 1541309367, 181892231, rs2070557, 156478109; 151892231, rs7278257, 111221332, 151892231, rs7278257, 1541309367, 151892231, 157278257, 156478109; 151892231, 1511221332, 1541309367; 151892231, 1511221332, rs6478109; 151892231, 1541309367, 156478109; 1512934476, rs9806914, 152297437, 1512934476, rs9806914, 12070557, 1512934476, rs9806914, 187278257, 1512934476, rs9806914, 1311221332; 1512934476, rs9806914, 1541309367; 1512934476, rs9806914, 156478109; 1512934476, rs2297437, 152070557; 1512934476, rs2297437, 157278257; 1512934476, rs2297437, 1311221332; 1512934476, rs2297437, 141309367, 1512934476, rs2297437, 156478109, 1812934476, rs2070557, 17278257, 1512934476, rs2070557, 111221332; 1512934476, rs2070557, 141309367; 1512934476, rs2070557, 156478109; 1512934476, rs7278257, 1311221332; 1812934476, rs7278257, 1s41309367, 1512934476, rs7278257, 1s6478109, 1512934476, rs11221332, rs41309367; 1812934476, rs11221332, 156478109, 1512934476, rs41309367, rs6478109; 159806914, 152297437, 152070557, 159806914, 152297437, 157278257, 159806914, 152297437, 1511221332; 159806914, 152297437, 1541309367, 159806914, 52297437, rs6478109; (257) 159806914, rs2070557, 157278257; (258) rs9806914, rs2070557, 1511221332; (259) 159806914, rs2070557, 1541309367; (260) 1rs9806914, rs2070557, 156478109; (261) 159806914, rs7278257, 1511221332; (262) 159806914, rs7278257, 1541309367; (263) 159806914, rs7278257, 156478109; (264) 159806914, rs11221332, rs41309367; (265) 159806914, rs11221332, rs6478109; (266) 1rs9806914, rs41309367, rs6478109; (267) 152297437, rs2070557, 157278257; (268) 152297437, rs2070557, 1511221332; (269) 152297437, 152070557, 1541309367; (270) 12297437, 152070557, 156478109; (271) 152297437, rs7278257, 1511221332; (272) 152297437, rs7278257, 1541309367; (273) 152297437, rs7278257, 156478109; (274) 152297437, 1511221332, 1s41309367; (275) 152297437, 1511221332, rs6478109; (276) 152297437, rs41309367, rs6478109; (277) 152070557, rs7278257, 1511221332; (278) 152070557, rs7278257, 1541309367; (279) 152070557, rs7278257, 156478109; (280) 152070557, rs11221332, rs41309367; (281) 1rs2070557, rs11221332, rs6478109; (282) 1rs2070557, rs41309367, rs6478109; (283) 1rs7278257, rs11221332, rs41309367; (284) 1rs7278257, rs11221332, rs6478109; (285) 157278257, rs41309367, rs6478109; or (286) 1511221332, rs41309367, rs6478109. 15. The genotype of embodiment 14, wherein the rs7278257 is replaced with rs56124762. 16. The genotype of embodiment 14, wherein the rs7278257 is replaced with rs2070558. 17. The genotype of embodiment 14, wherein the rs7278257 is replaced with rs2070561. 18. The genotype of embodiments 5-6, wherein the genotype comprises at least two polymorphisms selected from imm_9_116608587, imm_11_127948309, and rs1892231. 19. The genotype of embodiments 5-6, wherein the genotype comprises at least two polymorphisms selected from imm_9_116608587, imm_11_127948309, and rs9806914. 20. The genotype of embodiments 5-6, wherein the genotype comprises at least two polymorphisms selected from imm_9 116608587, imm 11 127948309, and imm 21 44478192. 21. The genotype of embodiments 5-6, wherein the genotype comprises at least two polymorphisms selected from imm_9 116608587, imm 11 127948309, and imm 21 44479552. 22. The genotype of embodiments 5-6, wherein the genotype comprises at least two polymorphisms selected from imm_9_ 116608587, rs1892231, and rs9806914. 23. The genotype of embodiments 5-6, wherein the genotype comprises at least two polymorphisms selected from imm_9_116608587, rs1892231, and imm_21_44478192. 24. The genotype of embodiments 5-6, wherein the genotype comprises at least two polymorphisms selected from imm_9_116608587, rs1892231, and imm_21_44479552. 25. The genotype of embodiments 5-6, wherein the genotype comprises at least two polymorphisms selected from imm_9_116608587, rs9806914, and imm_21_44478192. 26. The genotype of embodiments 5-6, wherein the genotype comprises at least two polymorphisms selected from imm_9_116608587, rs9806914, and imm_21_44479552. 27. The genotype of embodiments 5-6, wherein the genotype comprises at least two polymorphisms selected from imm_9 116608587, imm 21 44478192, andimm 21 44479552. 28. The genotype of embodiments 5-6, wherein the genotype comprises at least two polymorphisms selected from imm_11_127948309, rs1892231, and rs9806914. 29. The genotype of embodiments 5-6, wherein the genotype comprises at least two polymorphisms selected from imm_11_127948309, rs1892231, and imm_21_44478192. 30. The genotype of embodiments 5-6, wherein the genotype comprises at least two polymorphisms selected from imm_11_127948309, rs1892231, and imm_21_44479552. 31. The genotype of embodiments 5-6, wherein the genotype comprises at least two polymorphisms selected from imm_11_127948309, rs9806914, and imm_21_44478192. 32. The genotype of embodiments 5-6, wherein the genotype comprises at least two polymorphisms selected from imm_11 127948309, rs9806914, and imm_ 21 44479552. 33. The genotype of embodiments 5-6, wherein the genotype comprises at least two polymorphisms selected from imm_11 127948309, imm_21 44478192, and imm 21 44479552. 34. The genotype of embodiments 5-6, wherein the genotype comprises at least two polymorphisms selected from rs1892231, rs9806914, and imm_21_44478192. 35. The genotype of embodiments 5-6, wherein the genotype comprises at least two polymorphisms selected from rs1892231, rs9806914, and imm_21_44479552. 36. The genotype of embodiments 5-6, wherein the genotype comprises at least two polymorphisms selected from rs1892231, imm_21_44478192, and imm_21_44479552. 37. The genotype of embodiments 5-6, wherein the genotype comprises at least two polymorphisms selected from rs9806914, imm_21_44478192, and imm_21_44479552. 38. The genotype of embodiments 5-6, wherein the genotype comprises at least two polymorphisms selected from rs6478109, rs56124762, and rs1892231. 39. The genotype of embodiments 5-6, wherein the genotype comprises at least two polymorphisms selected from rs6478109, rs56124762, and rs16901748. 40. The genotype of embodiments 5-6, wherein the genotype comprises at least two polymorphisms selected from rs6478109, rs1892231, and rs16901748. 41. The genotype of embodiments 5-6, wherein the genotype comprises at least two polymorphisms selected from rs56124762, rs1892231, and rs16901748. 42. The genotype of embodiments 5-6, wherein the genotype comprises at least two polymorphisms selected from rs6478109, rs2070558, and rs1892231. 43. The genotype of embodiments 5-6, wherein the genotype comprises at least two polymorphisms selected from rs6478109, rs2070558, and rs16901748. 44. The genotype of embodiments 5-6, wherein the genotype comprises at least two polymorphisms selected from rs6478109, rs1892231, and rs16901748. 45. The genotype of embodiments 5-6, wherein the genotype comprises at least two polymorphisms selected from rs2070558, rs1892231, and rs16901748. 46. The genotype of embodiments 5-6, wherein the genotype comprises at least two polymorphisms selected from rs6478109, rs2070561, and rs1892231. 47. The genotype of embodiments 5-6, wherein the genotype comprises at least two polymorphisms selected from rs6478109, rs2070561 , and rs16901748. 48. The genotype of embodiments 5-6, wherein the genotype comprises at least two polymorphisms selected from rs6478109, rs1892231, and rs16901748. 49. The genotype of embodiments 5-6, wherein the genotype comprises at least two polymorphisms selected from rs2070561, rs1892231, and rs16901748. 50. The genotype of embodiments 1-49, wherein the genotype comprises a minor allele provided in Table 1 for at least one polymorphism. 51. The genotype of embodiments 1-49, wherein the genotype comprises a major allele provided in Table 1 for at least one polymorphism. 52. The genotype of embodiments 1-51, wherein a presence of the genotype is predictive of a positive therapeutic response to a treatment with an inhibitor of TL1A activity of expression at a positive predictive value of at least about 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%. 53. The genotype of embodiments 1-55, wherein a presence of the genotype is predictive of a positive therapeutic response to a treatment with an inhibitor of TL1A activity of expression with a specificity of at least about 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%.

[0087] Aspects disclosed herein provide genotypes that are associated with, and therefore indicative of, a subject having or being susceptible to developing a particular disease or condition, or a subclinical phenotype thereof. In addition, the genotypes disclosed herein are associated with an increase TNFSF15 (TL1A) expression or activity. Thus, the genotypes are indicative that the subject will have a positive therapeutic response to an inhibitor of TL1IA activity or expression. Table 1 provides exemplary polymorphisms associated with, and therefore predictive of, a positive therapeutic response to an inhibitor of 7NFSF15 (TL1A) expression or activity. The term, “positive therapeutic response” refers to a reduction or an elimination of at least one symptom of the disease or the condition (e.g., Cohn’s disease) after induction of a therapy (e.g., anti-TL1A antibody).

[0088] The instant disclosure provides models comprising 3 polymorphisms (e.g, “3-SNP Models”) that, when detected in a sample obtained from a subject, indicate a positive therapeutic response in the subject to a treatment, such as with an inhibitor of TL1A activity or expression. Non-limiting examples of models described herein include Model A (rs6478109, rs7278257, and 151892231); Model B (156478109, 12070557, and rs9806914), Model C (rs6478109, 157935393, and rs1892231); Model D (rs6478109, rs7935393, and 59806914); Model E (rs6478109, rs9806914, and rs16901748); Model F (rs6478109, rs16901748, and rs2297437); Model G (rs6478109, rs1892231, and rs16901748);, Model H (rs6478109, rs2070557, and 1s7935393); Model I (rs6478109, rs7278257, and 137935393), Model J (rs6478109, 1s9806914, and rs1892231); and Model K (rs6478109, rs7278257, and rs16901748). METHODS Methods of Detection

[0089] Methods disclosed herein for detecting a genotype in a sample from a subject comprise analyzing the genetic material in the sample to detect at least one of a presence, an absence, and a quantity of a nucleic acid sequence encompassing the genotype of interest. In some embodiments, the sample is assayed to measure a presence, absence or quantity of at least three polymorphisms. In some embodiments, the sample is assayed to measure a presence, absence, or quantity of at least four polymorphisms. In some embodiments, the sample is assayed to measure a presence, absence, or quantity of at least five polymorphisms. In some embodiments, at least three genotypes are detected, using the methods described herein.

[0090] In some cases, the nucleic acid sequence comprises DNA. In some instances, the nucleic acid sequence comprises a denatured DNA molecule or fragment thereof. In some instances, the nucleic acid sequence comprises DNA selected from: genomic DNA, viral DNA, mitochondrial DNA, plasmid DNA, amplified DNA, circular DNA, circulating DNA, cell-free DNA, or exosomal DNA. In some instances, the DNA is single-stranded DNA (ssDNA), double- stranded DNA, denaturing double-stranded DNA, synthetic DNA, and combinations thereof. The circular DNA may be cleaved or fragmented. In some instances, the nucleic acid sequence comprises RNA. In some instances, the nucleic acid sequence comprises fragmented RNA. In some instances, the nucleic acid sequence comprises partially degraded RNA. In some instances, the nucleic acid sequence comprises a microRNA or portion thereof. In some instances, the nucleic acid sequence comprises an RNA molecule or a fragmented RNA molecule (RNA fragments) selected from: a microRNA (miRNA), a pre-miRNA, a pri-miRNA, a mRNA, a pre- mRNA, a viral RNA, a viroid RNA, a virusoid RNA, circular RNA (circRNA), a ribosomal RNA (rRNA), a transfer RNA (tRNA), a pre-tRNA, a long non-coding RNA (IncRNA), a small nuclear RNA (snRNA), a circulating RNA, a cell-free RNA, an exosomal RNA, a vector- expressed RNA, an RNA transcript, a synthetic RNA, and combinations thereof.

[0091] Nucleic acid-based detection techniques that may be useful for the methods herein include quantitative polymerase chain reaction (qPCR), gel electrophoresis, immunochemistry, in situ hybridization such as fluorescent in situ hybridization (FISH), cytochemistry, and next generation sequencing. In some embodiments, the methods involve TagMan™ qPCR, which involves a nucleic acid amplification reaction with a specific primer pair, and hybridization of the amplified nucleic acids with a hydrolysable probe specific to a target nucleic acid.

[0092] In some instances, the methods involve hybridization and / or amplification assays that include, but are not limited to, Southern or Northern analyses, polymerase chain reaction analyses, and probe arrays. Non-limiting amplification reactions include, but are not limited to, qPCR, self-sustained sequence replication, transcriptional amplification system, Q-Beta Replicase, rolling circle replication, or any other nucleic acid amplification known in the art. As discussed, reference to qPCR herein includes use of TagMan™ methods. An additional exemplary hybridization assay includes the use of nucleic acid probes conjugated or otherwise immobilized on a bead, multi-well plate, or other substrate, wherein the nucleic acid probes are configured to hybridize with a target nucleic acid sequence of a genotype provided herein. A non-limiting method is one employed in Anal Chem. 2013 Feb 5; 85(3):1932-9.

[0093] In some embodiments, detecting the presence or absence of a genotype comprises sequencing genetic material from the subject. Sequencing can be performed with any appropriate sequencing technology, including but not limited to single-molecule real-time (SMRT) sequencing, Polony sequencing, sequencing by ligation, reversible terminator sequencing, proton detection sequencing, ion semiconductor sequencing, nanopore sequencing, electronic sequencing, pyrosequencing, Maxam-Gilbert sequencing, chain termination (e.g., Sanger) sequencing, +S sequencing, or sequencing by synthesis. Sequencing methods also include next- generation sequencing, e.g., modern sequencing technologies such as Illumina sequencing (e.g., Solexa), Roche 454 sequencing, Ion torrent sequencing, and SOLID sequencing. In some cases, next-generation sequencing involves high-throughput sequencing methods. Additional sequencing methods available to one of skill in the art may also be employed.

[0094] In some instances, a number of nucleotides that are sequenced are at least 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 100, 150, 200, 300, 400, 500, 2000, 4000, 6000, 8000, 10000, 20000, 50000, 100000, or more than 100000 nucleotides. In some instances, the number of nucleotides sequenced is in a range of about 1 to about 100000 nucleotides, about 1 to about 10000 nucleotides, about 1 to about 1000 nucleotides, about 1 to about 500 nucleotides, about 1 to about 300 nucleotides, about 1 to about 200 nucleotides, about 1 to about 100 nucleotides, about 5 to about 100000 nucleotides, about 5 to about 10000 nucleotides, about 5 to about 1000 nucleotides, about 5 to about 500 nucleotides, about 5 to about 300 nucleotides, about 5 to about 200 nucleotides, about 5 to about 100 nucleotides, about 10 to about 100000 nucleotides, about 10 to about 10000 nucleotides, about 10 to about 1000 nucleotides, about 10 to about 500 nucleotides, about 10 to about 300 nucleotides, about 10 to about 200 nucleotides, about 10 to about 100 nucleotides, about 20 to about 100000 nucleotides, about 20 to about 10000 nucleotides, about 20 to about 1000 nucleotides, about 20 to about 500 nucleotides, about 20 to about 300 nucleotides, about 20 to about 200 nucleotides, about 20 to about 100 nucleotides, about 30 to about 100000 nucleotides, about 30 to about 10000 nucleotides, about 30 to about 1000 nucleotides, about 30 to about 500 nucleotides, about 30 to about 300 nucleotides, about 30 to about 200 nucleotides, about 30 to about 100 nucleotides, about 50 to about 100000 nucleotides, about 50 to about 10000 nucleotides, about 50 to about 1000 nucleotides, about 50 to about 500 nucleotides, about 50 to about 300 nucleotides, about 50 to about 200 nucleotides, or about 50 to about 100 nucleotides.

[0095] Exemplary probes comprise a nucleic acid sequence of at least 10 contiguous nucleic acids provided in any one of SEQ ID NOS: 1-48, or 57-59, including the nucleobase indicated with a non-nucleobase letter (e.g, R, N, S), or a reverse complement thereof. In some instances, the probes may be used to detect the polymorphisms provided in Table 1, wherein the probe comprises a nucleic acid sequence of at least 10 contiguous nucleic acids provided in a corresponding SEQ ID NO or reverse complement thereof, the 10 contiguous nucleic acids comprising the “risk allele” also provided in Table 1 at a nucleoposition indicated with the non- nucleobase letter, or reverse complement thereof. In some embodiments, the probe comprises at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to any one of SEQ ID NOS: 1-48, or 57-59, or its reverse complement. In some instances, forward and reverse primers are used to amplify the target nucleic acid sequence. Forward and reverse primers may comprise a nucleic acid sequence flanking the risk allele provided in Table 1 corresponding to the nucleic acid sequence provided in any one of SEQ ID NOS: 1-48, or 57-59, or a reverse complement thereof.

[0096] Examples of molecules that are utilized as probes include, but are not limited to, RNA and DNA. In some embodiments, the term “probe” with regards to nucleic acids, refers to any molecule that is capable of selectively binding to a specifically intended target nucleic acid sequence. In some instances, probes are specifically designed to be labeled, for example, with a radioactive label, a fluorescent label, an enzyme, a chemiluminescent tag, a colorimetric tag, or other labels or tags that are known in the art. In some instances, the fluorescent label comprises a fluorophore. In some instances, the fluorophore is an aromatic or heteroaromatic compound. In some instances, the fluorophore is a pyrene, anthracene, naphthalene, acridine, stilbene, benzoxazole, indole, benzindole, oxazole, thiazole, benzothiazole, canine, carbocyanine, salicylate, anthranilate, xanthenes dye, coumarin. Exemplary xanthene dyes include, e.g., fluorescein and rhodamine dyes. Fluorescein and rhodamine dyes include, but are not limited to 6-carboxyfluorescein (FAM), 2'7'-dimethoxy-4'5'-dichloro-6-carboxyfluorescein (JOE), tetrachlorofluorescein (TET), 6-carboxyrhodamine (R6G), N,N,N; N'-tetramethyl-6- carboxyrhodamine (TAMRA), 6-carboxy-X-rhodamine (ROX). Suitable fluorescent probes also include the naphthylamine dyes that have an amino group in the alpha or beta position. For example, naphthylamino compounds include 1-dimethylaminonaphthyl-5-sulfonate, 1-anilino-8- naphthalene sulfonate and 2-p-toluidinyl-6-naphthalene sulfonate, 5-(2'- aminoethyl)aminonaphthalene-1-sulfonic acid (EDANS). Exemplary coumarins include, e.g., 3- phenyl-7-isocyanatocoumarin; acridines, such as 9-isothiocyanatoacridine and acridine orange; N-(p-(2-benzoxazolyl)phenyl) maleimide; cyanines, such as, e.g., indodicarbocyanine 3 (Cy3), indodicarbocyanine 5 (CyS5), indodicarbocyanine 5.5 (Cy5.5), 3-(-carboxy-pentyl)-3'-ethyl-5,5'- dimethyloxacarbocyanine (CyA); 1H, 5H, 11H, 15H-Xantheno[2,3, 4-ij: 5,6, 7-i'j']diquinolizin- 18-ium, 9-[2 (or 4)-[[[6-[2,5-dioxo-1-pyrrolidiny])oxy]-6-oxohexyl Jamino]sulfonyl]-4 (or 2)- sulfophenyl]-2,3, 6,7, 12,13, 16,17-octahydro-inner salt (TR or Texas Red); or BODIPYTM dyes. In some cases, the probe comprises FAM as the dye label.

[0097] In some instances, primers and / or probes described herein for detecting a target nucleic acid are used in an amplification reaction. In some instances, the amplification reaction is qPCR. An exemplary qPCR is a method employing a TagMan™ assay. Non-limiting examples of primer pairs useful for detecting one or more polymorphisms described herein are provided in Table 6, below. Table 6. Exemplary Primer Sequences ¥T+TG GCA | +TIGCGGA TGAAAGT (SEQ = GACAGAGG (SEQ | (SEQ ID NO: (SEQ ID NO: Wt_Probe_He | Mut_Probe_F rsID Forward Primer Reverse Primer x AM TG+C +AG+A | TG+C +AGG | TGCTTCTGGAAG | TGAGGTTCAAAAT | +T+TG GGA +TTG GGA | 15647810 | TGAAAGT (SEQ GACAGAGG (SEQ | (SEQID NO: (SEQ ID NO: 9 "ID NO: 364101 ID NO: 364111) ' 364121 364131 AT +T+TG +G+A+A ATT TGG haba wll SLAY AGGG+AA +C+A+A GGG | TTCATGTG(SEQ | (SEQIDNO: (SEQIDNO: AA(SEQID TTT TCA ATG CAC GTCATCATCGCT | AGA TTT AAG GA | 15189223 | TTCATGTG (SEQ (SEQ ID NO: AAG(SEQIDNO: © GA(SEQID ' (SEQIDNO: | 15189223 | TTCATGTG (SEQ | (SEQ ID NO: © (SEQ ID NO: AA(SEQID ’ ID NO: 364102 364112) 364122 NO: 364132 CCT AAG GAG AGHA A+T+A | T+AG +AA+T CTGGATGCTCAC | ACT TTT AGT TCT | +CA+C A+AG | +C+C+A CAA | 13793539 | AGGTTTG (SEQ ID | AAG (SEQ ID NO: GA (SEQ ID (SEQ ID NO: 3 NO: 364103) 364113) NO: 364123) 364133) 3 J NO: 364103 * 364113) NO: 364123) 364133 “Wt_Probe_Hex” and “Mut_Probe_FAM” mean “Wild type_probes_tagged with HEX reporter dye” and“Mut_probe_tagged with FAM reporter dye”, respectively. "+" stands for LNA bases (Locked nucleotides), which are analogues that are modified at 2'-O, 4'-C and form a bridge. This bridge results in restricted base pairing giving room to adjust the Tm as needed between the probes. Thus, + A, + T, + C or + G signify A, T, G or C bases are added on the modified backbone.

[0098] In some instances, qPCR comprises using an intercalating dye. Examples of intercalating dyes include SYBR green I, SYBR green II, SYBR gold, ethidium bromide, methylene blue, Pyronin Y, DAPI, acridine orange, Blue View or phycoerythrin. In some instances, the intercalating dye is SYBR.

[0099] In some instances, a number of amplification cycles for detecting a target nucleic acid in an amplification assay is about 5 to about 30 cycles. In some instances, the number of amplification cycles for detecting a target nucleic acid is at least about 5 cycles. In some instances, the number of amplification cycles for detecting a target nucleic acid is at most about 30 cycles. In some instances, the number of amplification cycles for detecting a target nucleic acid is about 5 to about 10, about 5 to about 15, about 5 to about 20, about 5 to about 25, about 5 to about 30, about 10 to about 15, about 10 to about 20, about 10 to about 25, about 10 to about 30, about 15 to about 20, about 15 to about 25, about 15 to about 30, about 20 to about 25, about 20 to about 30, or about 25 to about 30 cycles.

[0100] In one aspect, the methods provided herein for determining the presence, absence, and / or quantity of a nucleic acid sequence from a particular genotype comprise an amplification reaction such as qPCR. In an exemplary method, genetic material is obtained from a sample of a subject, e.g., a sample of blood or serum. In certain embodiments where nucleic acids are extracted, the nucleic acids are extracted using any technique that does not interfere with subsequent analysis. In certain embodiments, this technique uses alcohol precipitation using ethanol, methanol, or isopropyl alcohol. In certain embodiments, this technique uses phenol, chloroform, or any combination thereof. In certain embodiments, this technique uses cesium chloride. In certain embodiments, this technique uses sodium, potassium or ammonium acetate or any other salt commonly used to precipitate DNA. In certain embodiments, this technique utilizes a column or resin based nucleic acid purification scheme such as those commonly sold commercially, one non-limiting example would be the GenElute Bacterial Genomic DNA Kit available from Sigma Aldrich. In certain embodiments, after extraction the nucleic acid is stored in water, Tris buffer, or Tris-EDTA buffer before subsequent analysis. In an exemplary embodiment, the nucleic acid material is extracted in water. In some cases, extraction does not comprise nucleic acid purification.

[0101] In the exemplary qPCR assay, the nucleic acid sample is combined with primers and probes specific for a target nucleic acid that may or may not be present in the sample, and a DNA polymerase. An amplification reaction is performed with a thermal cycler that heats and cools the sample for nucleic acid amplification, and illuminates the sample at a specific wavelength to excite a fluorophore on the probe and detect the emitted fluorescence. For TagMan™ methods, the probe may be a hydrolysable probe comprising a fluorophore and quencher that is hydrolyzed by DNA polymerase when hybridized to a target nucleic acid. In some cases, the presence of a target nucleic acid is determined when the number of amplification cycles to reach a threshold value is less than 30, 29, 28, 27, 26, 25, 24, 23, 22, 21, or 20 cycles.

[0102] In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 1 comprising a non-reference allele at nucleoposition 501 within SEQ ID NO: 1. In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 1 comprising a “G” or an “A” allele at nucleoposition 501 within SEQ ID NO: 1. In some embodiments, detecting the at least 10 contiguous nucleic acid molecules comprising a “G” or an “A” allele at nucleoposition 501 within SEQ ID NO: 1 is sufficient to detect the polymorphism at rs11897732.

[0103] In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 2 comprising non-reference allele at nucleoposition 501 within SEQ ID NO: 2. In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 2 comprising an “A” or a “G” allele at nucleoposition 501 within SEQ ID NO: 2. In some embodiments, detecting the at least 10 contiguous nucleic acid molecules comprising an “A” or a “G” allele at nucleoposition 501 within SEQ ID NO: 2 is sufficient to detect the polymorphism at rs6740739.

[0104] In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 3 comprising a non-reference allele at nucleoposition 501 within SEQ ID NO: 3. In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 3 comprising a “G” or a “C” allele at nucleoposition 501 within SEQ ID NO: 3. In some embodiments, detecting the at least 10 contiguous nucleic acid molecules comprising a “G” or a “C” allele at nucleoposition 501 within SEQ ID NO: 3 is sufficient to detect the polymorphism at rs17796285.

[0105] In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 4 comprising a non-reference allele at nucleoposition 501 within SEQ ID NO: 4. In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 4 comprising a “C” or an “A” allele at nucleoposition 501 within SEQ ID NO: 4. In some embodiments, detecting the at least 10 contiguous nucleic acid molecules comprising a “C” or an “A” allele at nucleoposition 501 within SEQ ID NO: 4 is sufficient to detect the polymorphism at rs7935393.

[0106] In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 5 comprising a non-reference allele at nucleoposition 501 within SEQ ID NO: 5. In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 5 comprising a “G” or an “A” allele at nucleoposition 501 within SEQ ID NO: 5. In some embodiments, detecting the at least 10 contiguous nucleic acid molecules comprising a “G” of an “A” allele at nucleoposition 501 within SEQ ID NO: 5 is sufficient to detect the polymorphism at rs12934476.

[0107] In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 6 comprising a non-reference allele at nucleoposition 501 within SEQ ID NO: 6. In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 6 comprising an “A” or a “C” allele at nucleoposition 501 within SEQ ID NO: 6. In some embodiments, detecting the at least 10 contiguous nucleic acid molecules comprising an “A” or a “C” allele at nucleoposition 501 within SEQ ID NO: 6 is sufficient to detect the polymorphism at rs12457255.

[0108] In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 7 comprising a non-reference allele at nucleoposition 501 within SEQ ID NO: 7. In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 7 comprising an “A” or a “T” allele at nucleoposition 501 within SEQ ID NO: 7. In some embodiments, detecting the at least 10 contiguous nucleic acid molecules comprising an “A” or a “T” allele at nucleoposition 501 within SEQ ID NO: 7 is sufficient to detect the polymorphism at 1s2070557.

[0109] In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 8 comprising a non-reference allele at nucleoposition 501 within SEQ ID NO: 8. In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 8 comprising an “A” or a “G” allele at nucleoposition 501 within SEQ ID NO: 8. In some embodiments, detecting the at least 10 contiguous nucleic acid molecules comprising an “A” or “G” allele at nucleoposition 501 within SEQ ID NO: 8 is sufficient to detect the polymorphism at rs4246905.

[0110] In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 9 comprising a non-reference allele at nucleoposition 501 within SEQ ID NO: 9. In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 9 comprising an “A” or a “G” allele at nucleoposition 501 within SEQ ID NO: 9. In some embodiments, detecting the at least 10 contiguous nucleic acid molecules comprising an “A” or a “G” allele at nucleoposition 501 within SEQ ID NO: 9 is sufficient to detect the polymorphism at rs10974900.

[0111] In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 10 comprising a non-reference allele at nucleoposition 501 within SEQ ID NO: 10. In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 10 comprising a “C” or an “A” allele at nucleoposition 501 within SEQ ID NO: 10. In some embodiments, detecting the at least 10 contiguous nucleic acid molecules comprising a “C” or an “A” allele at nucleoposition 501 within SEQ ID NO: 10 is sufficient to detect the polymorphism at rs12434976.

[0112] In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 11 comprising a non-reference allele at nucleoposition 501 within SEQ ID NO: 11. In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 11 comprising an “A” or a “C” allele at nucleoposition 501 within SEQ ID NO: 11. In some embodiments, detecting the at least 10 contiguous nucleic acid molecules comprising an “A” or a “C” allele at nucleoposition 501 within SEQ ID NO: 11 is sufficient to detect the polymorphism at rs16901748.

[0113] In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 12 comprising a non-reference allele at nucleoposition 501 within SEQ ID NO: 12. In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 12 comprising an “A” or a “G” allele at nucleoposition 501 within SEQ ID NO: 12. In some embodiments, detecting the at least 10 contiguous nucleic acid molecules comprising an “A” or a “G” allele at nucleoposition 501 within SEQ ID NO: 12 is sufficient to detect the polymorphism at rs2815844.

[0114] In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 13 comprising a non-reference allele at nucleoposition 501 within SEQ ID NO: 13. In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 13 comprising a “G” or an “A” allele at nucleoposition 501 within SEQ ID NO: 13. In some embodiments, detecting the at least 10 contiguous nucleic acid molecules comprising a “G” or an “A” allele at nucleoposition 501 within SEQ ID NO: 13 is sufficient to detect the polymorphism at rs889702.

[0115] In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 14 comprising a non-reference allele at nucleoposition 501 within SEQ ID NO: 14. In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 14 comprising a “C” or an “A” allele at nucleoposition 501 within SEQ ID NO: 14. In some embodiments, detecting the at least 10 contiguous nucleic acid molecules comprising a “C” or an “A” allele at nucleoposition 501 within SEQ ID NO: 14 is sufficient to detect the polymorphism at rs2409750.

[0116] In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 15 comprising a non-reference allele at nucleoposition 501 within SEQ ID NO: 15. In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 15 comprising an “A” or a “G” allele at nucleoposition 501 within SEQ ID NO: 15. In some embodiments, detecting the at least 10 contiguous nucleic acid molecules comprising an “A” or “G” allele at nucleoposition 501 within SEQ ID NO: 15 is sufficient to detect the polymorphism at rs1541020.

[0117] In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 16 comprising a non-reference allele at nucleoposition 501 within SEQ ID NO: 16. In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 16 comprising a “T” or an “A” allele at nucleoposition 501 within SEQ ID NO: 16. In some embodiments, detecting the at least 10 contiguous nucleic acid molecules comprising a “T” or an “A” allele at nucleoposition 501 within SEQ ID NO: 16 is sufficient to detect the polymorphism at rs4942248.

[0118] In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 17 comprising a non-reference allele at nucleoposition 501 within SEQ ID NO: 17. In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 17 comprising a “G” or an “A” allele at nucleoposition 501 within SEQ ID NO: 17. In some embodiments, detecting the at least 10 contiguous nucleic acid molecules comprising a “G” or an “A” allele at nucleoposition 501 within SEQ ID NO: 17 is sufficient to detect the polymorphism at rs12934476.

[0119] In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 18 comprising a non-reference allele at nucleoposition 501 within SEQ ID NO: 18. In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 18 comprising an “A” or a “C” allele at nucleoposition 501 within SEQ ID NO: 18. In some embodiments, detecting the at least 10 contiguous nucleic acid molecules comprising an “A” or a “C” allele at nucleoposition 501 within SEQ ID NO: 18 is sufficient to detect the polymorphism at rs12457255.

[0120] In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 19 comprising a non-reference allele at nucleoposition 501 within SEQ ID NO: 19. In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 19 comprising an “A” or a “G” allele at nucleoposition 501 within SEQ ID NO: 19. In some embodiments, detecting the at least 10 contiguous nucleic acid molecules comprising an “A” or a “G” allele at nucleoposition 501 within SEQ ID NO: 19 is sufficient to detect the polymorphism at 152297437.

[0121] In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 20 comprising a non-reference allele at nucleoposition 501 within SEQ ID NO: 20.In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 20 comprising a “G” or an “A” allele at nucleoposition 501 within SEQ ID NO: 20. In some embodiments, detecting the at least 10 contiguous nucleic acid molecules comprising a “G” or an “A” allele at nucleoposition 501 within SEQ ID NO: 20 is sufficient to detect the polymorphism at rs41309367.

[0122] In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 21 comprising a non-reference allele at nucleoposition 501 within SEQ ID NO: 21. In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 21 comprising an “A” or a “G” allele at nucleoposition 501 within SEQ ID NO: 21. In some embodiments, detecting the at least 10 contiguous nucleic acid molecules comprising an “A” or a “G” allele at nucleoposition 501 within SEQ ID NO: 21 is sufficient to detect the polymorphism at rs10733509.

[0123] In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 22 comprising a non-reference allele at nucleoposition 501 within SEQ ID NO: 22. In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 22 comprising a “G” or an “A” allele at nucleoposition 501 within SEQ ID NO: 22. In some embodiments, detecting the at least 10 contiguous nucleic acid molecules comprising a “G” or an “A” allele at nucleoposition 501 within SEQ ID NO: 22 is sufficient to detect the polymorphism at rs10750376.

[0124] In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 23 comprising a non-reference allele at nucleoposition 501 within SEQ ID NO: 23. In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 23 comprising a “G” or an “A” allele at nucleoposition 501 within SEQ ID NO: 23. In some embodiments, detecting the at least 10 contiguous nucleic acid molecules comprising a “G” or an “A” allele at nucleoposition 501 within SEQ ID NO: 23 is sufficient to detect the polymorphism at rs10932456.

[0125] In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 24 comprising a non-reference allele at nucleoposition 501 within SEQ ID NO: 24. In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 24 comprising an “A” or a “G” allele at nucleoposition 501 within SEQ ID NO: 24. In some embodiments, detecting the at least 10 contiguous nucleic acid molecules comprising an “A” or a “G” allele at nucleoposition 501 within SEQ ID NO: 24 is sufficient to detect the polymorphism at rs1326860.

[0126] In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 25 comprising a “G” or an “A” allele at nucleoposition 501 within SEQ ID NO: 25. In some embodiments, detecting the at least 10 contiguous nucleic acid molecules comprising a “G” or an “A” allele at nucleoposition 501 within SEQ ID NO: 25 is sufficient to detect the polymorphism at rs1528663.

[0127] In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 26 comprising a non-reference allele at nucleoposition 501 within SEQ ID NO: 26. In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 26 comprising a “C” or an “A” allele at nucleoposition 501 within SEQ ID NO: 26. In some embodiments, detecting the at least 10 contiguous nucleic acid molecules comprising a “C” or an “A” allele at nucleoposition 501 within SEQ ID NO: 26 is sufficient to detect the polymorphism at rs1892231.

[0128] In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 27 comprising a non-reference allele at nucleoposition 501 within SEQ ID NO: 27. In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 27 comprising a “G” or an “A” allele at nucleoposition 501 within SEQ ID NO: 27. In some embodiments, detecting the at least 10 contiguous nucleic acid molecules comprising a “G” or an “A” allele at nucleoposition 501 within SEQ ID NO: 27 is sufficient to detect the polymorphism at rs951279.

[0129] In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 28 comprising a non-reference allele at nucleoposition 501 within SEQ ID NO: 28. In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 28 comprising an “A” or a “G” allele at nucleoposition 501 within SEQ ID NO: 28. In some embodiments, detecting the at least 10 contiguous nucleic acid molecules comprising an “A” or a “G” allele at nucleoposition 501 within SEQ ID NO: 28 is sufficient to detect the polymorphism at rs9806914.

[0130] In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 29 comprising a non-reference allele at nucleoposition 501 within SEQ ID NO: 29. In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 29 comprising a “C” or an “A” allele at nucleoposition 501 within SEQ ID NO: 29. In some embodiments, detecting the at least 10 contiguous nucleic acid molecules comprising a “C” or an “A” allele at nucleoposition 501 within SEQ ID NO: 29 is sufficient to detect the polymorphism at rs7935393.

[0131] In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 30 comprising a non-reference allele at nucleoposition 501 within SEQ ID NO: 30. In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 30 comprising a “G” or a “C” allele at nucleoposition 501 within SEQ ID NO: 30. In some embodiments, detecting the at least 10 contiguous nucleic acid molecules comprising a “G” or a “C” allele at nucleoposition 501 within SEQ ID NO: 30 is sufficient to detect the polymorphism at rs1690492.

[0132] In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 31 comprising a non-reference allele at nucleoposition 501 within SEQ ID NO: 31. In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 31 comprising a “G” or an “A” allele at nucleoposition 501 within SEQ ID NO: 31. In some embodiments, detecting the at least 10 contiguous nucleic acid molecules comprising a “G” or an “A” allele at nucleoposition 501 within SEQ ID NO: 31 is sufficient to detect the polymorphism at rs420726.

[0133] In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 32 comprising a non-reference allele at nucleoposition 501 within SEQ ID NO: 32. In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 32 comprising a “T” or an “A” allele at nucleoposition 501 within SEQ ID NO: 32. In some embodiments, detecting the at least 10 contiguous nucleic acid molecules comprising a “T” of an “A” allele at nucleoposition 501 within SEQ ID NO: 32 is sufficient to detect the polymorphism at rs7759385.

[0134] In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 33 comprising a non-reference allele at nucleoposition 501 within SEQ ID NO: 33. In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 33 comprising an “A” or a “G” allele at nucleoposition 501 within SEQ ID NO: 33. In some embodiments, detecting the at least 10 contiguous nucleic acid molecules comprising an “A” or a “G” allele at nucleoposition 501 within SEQ ID NO: 33 is sufficient to detect the polymorphism at rs10974900,

[0135] In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 34 comprising a non-reference allele at nucleoposition 501 within SEQ ID NO: 34. In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 34 comprising an “A” or a “G” allele at nucleoposition 501 within SEQ ID NO: 34. In some embodiments, detecting the at least 10 contiguous nucleic acid molecules comprising an “A” or a “G” allele at nucleoposition 501 within SEQ ID NO: 34 is sufficient to detect the polymorphism at rs1326860.

[0136] In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 35 comprising a non-reference allele at nucleoposition 501 within SEQ ID NO: 35. In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 35 comprising a “C” or a “G” allele at nucleoposition 501 within SEQ ID NO: 35. In some embodiments, detecting the at least 10 contiguous nucleic acid molecules comprising a “C” or a “G” allele at nucleoposition 501 within SEQ ID NO: 35 is sufficient to detect the polymorphism at rs2548147.

[0137] In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 36 comprising a non-reference allele at nucleoposition 501 within SEQ ID NO: 36. In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 36 comprising an “A” or a “G” allele at nucleoposition 501 within SEQ ID NO: 36. In some embodiments, detecting the at least 10 contiguous nucleic acid molecules comprising an “A” of a “G” allele at nucleoposition 501 within SEQ ID NO: 36 is sufficient to detect the polymorphism at rs2815844.

[0138] In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 37 comprising a non-reference allele at nucleoposition 501 within SEQ ID NO: 37. In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 37 comprising a “G” or an “A” allele at nucleoposition 501 within SEQ ID NO: 37. In some embodiments, detecting the at least 10 contiguous nucleic acid molecules comprising a “G” or an “A” allele at nucleoposition 501 within SEQ ID NO: 37 is sufficient to detect the polymorphism at rs889702.

[0139] In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 38 comprising a non-reference allele at nucleoposition 501 within SEQ ID NO: 38. In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 38 comprising an “A” or a “G” allele at nucleoposition 501 within SEQ ID NO: 38. In some embodiments, detecting the at least 10 contiguous nucleic acid molecules comprising an “A” or a “G” allele at nucleoposition 501 within SEQ ID NO: 38 is sufficient to detect the polymorphism at rs9806914.

[0140] In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 39 comprising a non-reference allele at nucleoposition 501 within SEQ ID NO: 39. In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 39 comprising an “A” or a “G” allele at nucleoposition 501 within SEQ ID NO: 39. In some embodiments, detecting the at least 10 contiguous nucleic acid molecules comprising an “A” or a “G” allele at nucleoposition 501 within SEQ ID NO: 39 is sufficient to detect the polymorphism at rs6478109.

[0141] In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 40 comprising a non-reference allele at nucleoposition 501 within SEQ ID NO: 40. In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 40 comprising a “C” or a “G” allele at nucleoposition 501 within SEQ ID NO: 40. In some embodiments, detecting the at least 10 contiguous nucleic acid molecules comprising a “C” or a “G” allele at nucleoposition 501 within SEQ ID NO: 40 is sufficient to detect the polymorphism at rs7278257.

[0142] In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 41 comprising a non-reference allele at nucleoposition 501 within SEQ ID NO: 41. In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 41 comprising an “A” or a “G” allele at nucleoposition 501 within SEQ ID NO: 41. In some embodiments, detecting the at least 10 contiguous nucleic acid molecules comprising an “A” or a “G” allele at nucleoposition 501 within SEQ ID NO: 41 is sufficient to detect the polymorphism at rs11221332.

[0143] In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 57 comprising a non-reference allele at nucleoposition 501 within SEQ ID NO: 57. In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 57 comprising an “A” or a “G” allele at nucleoposition 501 within SEQ ID NO: 57. In some embodiments, detecting the at least 10 contiguous nucleic acid molecules comprising an “A” or a “G” allele at nucleoposition 501 within SEQ ID NO: 57 is sufficient to detect the polymorphism at rs56124762.

[0144] In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 58 comprising a non-reference allele at nucleoposition 501 within SEQ ID NO: 58. In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 58comprising an “A” or a “G” allele at nucleoposition 501 within SEQ ID NO: 58. In some embodiments, detecting the at least 10 contiguous nucleic acid molecules comprising an “A” or a “G” allele at nucleoposition 501 within SEQ ID NO: 58 is sufficient to detect the polymorphism at rs2070558.

[0145] In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 59 comprising a non-reference allele at nucleoposition 501 within SEQ ID NO: 59. In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 59 comprising an “T” or a “C” allele at nucleoposition 501 within SEQ ID NO: 59. In some embodiments, detecting the at least 10 contiguous nucleic acid molecules comprising an “T” or a “C” allele at nucleoposition 501 within SEQ ID NO: 59 is sufficient to detect the polymorphism at rs2070561.

[0146] In some embodiments, one target nucleic acid (e.g., a polymorphism) is detected with the methods disclosed herein. In some embodiments, at least 2, 3, 4, 5, 6, 7, 8, 9, or 10 target nucleic acids are detected. In some embodiments, the at least 2, 3, 4, 5, 6, 7, 8, 9, or 10 target nucleic acids are detected in a single multiplexed assay. In some embodiments, when 4 target nucleic acids are detected in a sample from subject, 4 unique 3-polymorphism combinations are measured. In a non-limiting example, a sample (e.g., blood or plasma) obtained from a subject is contacted by 4 primer pairs, each primer pair individually adapted to amplify rs6487109, 1556124762, rs1892231, and rs16901748, respectively. A positive, negative, or indeterminate TNEFSF15 profile may depend, at least in part, on which of the 3-polymorphism combinations is detected in the sample, and / or whether the genotype is heterozygous or homozygous for the polymorphism. In this example, assaying 4 polymorphism means a total of 4 unique 3- polymorphisms may be detected in the patient sample, which are rs6478109, rs56124762, 151892231; 156478109, 1556124762, rs16901748;r s6478109, 151892231, 1516901748; and 1$56124762, rs1892231, 1s16901748. Each polymorphism detected may be heterozygous or homozygous.

[0147] To practice the methods and systems provided herein, genetic material may be extracted from a sample obtained from a subject, e.g., a sample of blood or serum. In certain embodiments where nucleic acids are extracted, the nucleic acids are extracted using any technique that does not interfere with subsequent analysis. In certain embodiments, this technique uses alcohol precipitation using ethanol, methanol or isopropyl alcohol. In certain embodiments, this technique uses phenol, chloroform, or any combination thereof. In certain embodiments, this technique uses cesium chloride. In certain embodiments, this technique uses sodium, potassium or ammonium acetate or any other salt commonly used to precipitate DNA. In certain embodiments, this technique utilizes a column or resin based nucleic acid purification scheme such as those commonly sold commercially, one non-limiting example would be the GenElute Bacterial Genomic DNA Kit available from Sigma Aldrich. In certain embodiments, after extraction the nucleic acid is stored in water, Tris buffer, or Tris-EDTA buffer before subsequent analysis. In an exemplary embodiment, the nucleic acid material is extracted in water. In some cases, extraction does not comprise nucleic acid purification. In certain embodiments, RNA may be extracted from cells using RNA extraction techniques including, for example, using acid phenol / guanidine isothiocyanate extraction (RNAzol B; Biogenesis), RNeasy RNA preparation kits (Qiagen) or PAXgene (PreAnalytix, Switzerland).

[0148] In some embodiments, methods of detecting a presence, absence, or level of a target protein (e.g., biomarker) in the sample obtained from the subject involve detecting protein activity or expression. In some embodiments, the target protein is TL1A, or a binding partner of TL1A such as Death Domain Receptor 3 (DcR3). A target protein may be detected by use of an antibody-based assay, where an antibody specific to the target protein is utilized. In some embodiments, antibody-based detection methods utilize an antibody that binds to any region of target protein. An exemplary method of analysis comprises performing an enzyme-linked immunosorbent assay (ELISA). The ELISA assay may be a sandwich ELISA or a direct ELISA. Another exemplary method of analysis comprises a single molecule array, e.g., Simoa. Other exemplary methods of detection include immunochistochemistry and lateral flow assay. Additional exemplary methods for detecting target protein include, but are not limited to, gel electrophoresis, capillary electrophoresis, high performance liquid chromatography (HPLC), thin layer chromatography (TLC), hyperdiffusion chromatography, and the like, or various immunological methods such as fluid or gel precipitation reactions, immunodiffusion (single or double), immunoelectrophoresis, radioimmunoassay (RIA), immunofluorescent assays, and Western blotting. In some embodiments, antibodies, or antibody fragments, are used in methods such as Western blots or immunofluorescence techniques to detect the expressed proteins. The antibody or protein can be immobilized on a solid support for Western blots and immunofluorescence techniques. Suitable solid phase supports or carriers include any support capable of binding an antigen or an antibody. Exemplary supports or carriers include glass, polystyrene, polypropylene, polyethylene, dextran, nylon, amylases, natural and modified celluloses, polyacrylamides, gabbros, and magnetite.

[0149] In some cases, a target protein may be detected by detecting binding between the target protein and a binding partner of the target protein. Non-limiting examples of binding partners to TL1A include DcR3, and Tumor necrosis factor receptor superfamily member 25 (TNR25). Exemplary methods of analysis of protein-protein binding comprise performing an assay in vivo or in vitro, or ex vivo. In some instances, the method of analysis comprises an assay such as a co-immunoprecipitation (co-IP), pull-down, crosslinking protein interaction analysis, labeled transfer protein interaction analysis, or Far-western blot analysis, FRET based assay, including, for example FRET-FLIM, a yeast two-hybrid assay, BiFC, or split luciferase assay.

[0150] Disclosed herein are methods of detecting a presence or a level of one or more serological markers in a sample obtained from a subject. In some embodiments, the one or more serological markers comprises anti-Saccharomyces cerevisiae antibody (ASCA), an anti- neutrophil cytoplasmic antibody (ANCA), antibody against E.coli outer membrane porin protein C (anti-OmpC), anti-chitin antibody, pANCA antibody, anti-I2 antibody, and anti-Cbir1 flagellin antibody. In some embodiments, the antibodies comprises immunoglobulin A (IgA), immunoglobulin G (IgG), immunoglobulin E (IgE), or immunoglobulin M (IgM), immunoglobulin D (IgD), or a combination thereof. Any suitable method for detecting a target protein or biomarker disclosed herein may be used to detect a presence, absence, or level of a serological marker. In some embodiments, the presence or the level of the one or more serological markers is detected using an enzyme-linked immunosorbent assay (ELISA), a single molecule array (Simoa), immunohistochemistry, internal transcribed spacer (ITS) sequencing, or any combination thereof. In some embodiments, the ELISA is a fixed leukocyte ELISA. In some embodiments, the ELISA is a fixed neutrophil ELISA. A fixed leukocyte or neutrophil ELISA may be useful for the detection of certain serological markers, such as those described in Saxon etal, A distinct subset of antineutrophil cytoplasmic antibodies is associated with inflammatory bowel disease, J. Allergy Clin. Immuno. 86:2; 202-210 (August 1990). In some embodiments, ELISA units (EU) are used to measure positivity of a presence or level of a serological marker (e.g, seropositivity), which reflects a percentage of a standard or reference value. In some embodiments, the standard comprises pooled sera obtained from well-characterized patient population (e.g., diagnosed with the same disease or condition the subject has, or is suspected of having) reported as being seropositive for the serological marker of interest. In some embodiments, the control or reference value comprises 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100 EU. In some instances, a quartile sum scores are calculated using, for example, the methods reported in Landers C J, Cohavy O, Misra R. et al., Selected loss of tolerance evidenced by Crohn’s disease-associated immune responses to auto- and microbial antigens. Gastroenterology (2002)123:689-699. Methods of Treatment

[0151] Disclosed herein are methods of treating a disease or condition, or a symptom of the disease or condition, in a subject, comprising administrating of therapeutic effective amount of one or more therapeutic agents to the subject. In some embodiments, the one or more therapeutic agents is administered to the subject alone (e.g., standalone therapy). In some embodiments, the one or more therapeutic agents is administered in combination with an additional agent. In some embodiments, the therapeutic agent is a first-line therapy for the disease or condition. In some embodiments, the therapeutic agent is a second-line, third-line, or fourth-line therapy, for the disease or condition. Therapeutic Agents

[0152] Aspects provided herein are methods of treating an inflammatory, fibrostenotic, or fibrotic disease or condition in a subject by administering a therapeutically effective amount of an inhibitor of TNF Superfamily Member 15 (TL1A) activity or expression to the subject, provided a genotype is detected in a sample obtained from the subject. In some cases, the TL1A protein comprises an amino acid sequence provided in any one of SEQ ID NOS: 50-52. In some cases, the TL1A protein comprises an amino acid sequence that is at least or about 70%, 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%. 97%, 98%, or 99% identical to any one of SEQ ID NOS: 50-52. In some embodiments, the inhibitor of TL1A activity or expression is effective to inhibit TL1A-DR3 binding. In some embodiments, the inhibitor of TL1A activity or expression comprises an allosteric modulator of TL1A. An allosteric modulator of TL1A may indirectly influence the effects TL1A on DR3, or TR6 / DcR3 on TL1A or DR3. The inhibitor of TL1A activity or expression may be a direct inhibitor or indirect inhibitor. Non-limiting examples of an inhibitor of TL1A expression include RNA to protein TL1A translation inhibitors, antisense oligonucleotides targeting the TNFSF / 5 mRNA (such as miRNAs, or siRNA), epigenetic editing (such as targeting the DNA-binding domain of TNFSF15, or post-translational modifications of histone tails and / or DNA molecules). Non-limiting examples of an inhibitor of TL1A activity include antagonists to the TL1A receptors, (DR3 and TR6 / DcR3), antagonists to TL1A antigen, and antagonists to gene expression products involved in TL1A mediated disease. Antagonists as disclosed herein, may include, but are not limited to, an anti-TL1A antibody, an anti- TL1A- binding antibody fragment, or a small molecule. The small molecule may be a small molecule that binds to TL1A or DR3. The anti-TL1A antibody may be monoclonal or polyclonal. The anti- TL1A antibody may be humanized or chimeric. The anti-TL1A antibody may be a fusion protein. The anti-TL1A antibody may be a blocking anti-TL1A antibody. A blocking antibody blocks binding between two proteins, e.g., a ligand and its receptor. Therefore, a TL1A blocking antibody includes an antibody that prevents binding of TL1A to DR3 and / or TR6 / DcR3 receptors. In a non-limiting example, the TL1A blocking antibody binds to DR3. In another example, the TL1A blocking antibody binds to DcR3. In some cases, the TL1A antibody is an anti-TL1A antibody that specifically binds to TL1A. In some cases, the TL1A antibody specifically binds to an epitope of the TL1A protein provided in any one of SEQ ID NOS: 50-52. In some cases, the TL1A protein comprises an amino acid sequence that is at least or about 70%, 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%. 97%, 98%, or 99% identical to any one of SEQ ID NOS: 50-52. The anti-TL1A antibody may comprise one or more of the antibody sequences of Table 2A or Table 2B. The anti-DR3 antibody may comprise an amino acid sequence that is at least 85% identical to any one of SEQ ID NOS: 258-270 and an amino acid sequence that is at least 85% identical to any one of SEQ ID NOS: 271-275. The anti-DR3 antibody may comprise an amino acid sequence comprising the HCDR1, HCDR2, HCDR3 domains of any one of SEQ ID NOS: 258-270 and the LCDR1, LCDR2, and LCDR3 domains of any one of SEQ ID NOS: 271-275.

[0153] In some embodiments, an anti-TL1A antibody comprises a heavy chain comprising three complementarity-determining regions: HCDR1, HCDR2, and HCDR3; and a light chain comprising three complementarity-determining regions: LCDR 1, LCDR2, and LCDR3. In some embodiments, the anti-TL1A antibody comprises a HCDR1 comprising SEQ ID NO: 109, a HCDR2 comprising SEQ ID NO: 110, a HCDR3 comprising SEQ ID NO: 111, a LCDR1 comprising SEQ ID NO: 112, a LCDR2 comprising SEQ ID NO: 113, and a LCDR3 comprising SEQ ID NO: 114. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 115 and a light chain (LC) variable domain comprising SEQ ID NO: 116.

[0154] In some embodiments, the anti-TL1A antibody comprises a HCDR1 comprising SEQ ID NO: 117, a HCDR2 comprising SEQ ID NO: 118, a HCDR3 comprising SEQ ID NO: 119, a LCDR1 comprising SEQ ID NO: 120, a LCDR2 comprising SEQ ID NO: 121, and a LCDR3 comprising SEQ ID NO: 122. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 123 and a light chain (LC) variable domain comprising SEQ ID NO: 124.

[0155] In some embodiments, the anti-TL1A antibody comprises a HCDR1 comprising SEQ ID NO: 125, a HCDR2 comprising SEQ ID NO: 126, a HCDR3 comprising SEQ ID NO: 127, a LCDRI1 comprising SEQ ID NO: 128, a LCDR2 comprising SEQ ID NO: 129, and a LCDR3 comprising SEQ ID NO: 130. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 131 and a light chain (LC) variable domain comprising SEQ ID NO: 132.

[0156] In some embodiments, the anti-TL1A antibody comprises a HCDR1 comprising SEQ ID NO: 133, a HCDR2 comprising SEQ ID NO: 134, a HCDR3 comprising SEQ ID NO: 135, a LCDRI1 comprising SEQ ID NO: 139, a LCDR2 comprising SEQ ID NO: 140, and a LCDR3 comprising SEQ ID NO: 141. In some cases, the anti-TL1A antibody comprises a HCDR1 comprising SEQ ID NO: 136, a HCDR2 comprising SEQ ID NO: 137, a HCDR3 comprising SEQ ID NO: 138, a LCDR1 comprising SEQ ID NO: 139, a LCDR2 comprising SEQ ID NO: 140, and a LCDR3 comprising SEQ ID NO: 141. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 142 and a light chain (LC) variable domain comprising SEQ ID NO: 143. In some cases, the anti-TL1A antibody comprises a heavy chain comprising SEQ ID NO: 144. In some cases, the anti-TL1A antibody comprises a light chain comprising SEQ ID NO: 145.

[0157] In some embodiments, the anti-TL1A antibody comprises a HCDR1 comprising SEQ ID NO: 146, a HCDR2 comprising SEQ ID NO: 147, a HCDR3 comprising SEQ ID NO: 148, a LCDRI1 comprising SEQ ID NO: 149, a LCDR2 comprising SEQ ID NO: 150, and a LCDR3 comprising SEQ ID NO: 151. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 152 and a light chain (LC) variable domain comprising SEQ ID NO: 153.

[0158] In some embodiments, the anti-TL1A antibody comprises a HCDR1 comprising SEQ ID NO: 154, a HCDR2 comprising SEQ ID NO: 155, a HCDR3 comprising SEQ ID NO: 156, a LCDR1 comprising SEQ ID NO: 157, a LCDR2 comprising SEQ ID NO: 158, and a LCDR3 comprising SEQ ID NO: 159. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 160 and a light chain (LC) variable domain comprising SEQ ID NO: 161.

[0159] In some embodiments, the anti-TL1A antibody comprises a HCDR1 comprising SEQ ID NO: 162, a HCDR2 comprising SEQ ID NO: 164, a HCDR3 comprising SEQ ID NO: 165, a LCDR1 comprising SEQ ID NO: 167, a LCDR2 comprising SEQ ID NO: 169, and a LCDR3 comprising SEQ ID NO: 170. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 171 and a light chain (LC) variable domain comprising SEQ ID NO: 175. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 171 and a light chain (LC) variable domain comprising SEQ ID NO: 176. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 171 and a light chain (LC) variable domain comprising SEQ ID NO: 177. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 171 and a light chain (LC) variable domain comprising SEQ ID NO: 178.

[0160] In some embodiments, the anti-TL1A antibody comprises a HCDR1 comprising SEQ ID NO: 162, a HCDR2 comprising SEQ ID NO: 164, a HCDR3 comprising SEQ ID NO: 165, a LCDRI1 comprising SEQ ID NO: 168, a LCDR2 comprising SEQ ID NO: 169, and a LCDR3 comprising SEQ ID NO: 170. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 171 and a light chain (LC) variable domain comprising SEQ ID NO: 179. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 171 and a light chain (LC) variable domain comprising SEQ ID NO: 180. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 171 and a light chain (LC) variable domain comprising SEQ ID NO: 181. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 171 and a light chain (LC) variable domain comprising SEQ ID NO: 182.

[0161] In some embodiments, the anti-TL1A antibody comprises a HCDR1 comprising SEQ ID NO: 162, a HCDR2 comprising SEQ ID NO: 164, a HCDR3 comprising SEQ ID NO: 165, a LCDRI1 comprising SEQ ID NO: 167, a LCDR2 comprising SEQ ID NO: 169, and a LCDR3 comprising SEQ ID NO: 170. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 172 and a light chain (LC) variable domain comprising SEQ ID NO: 175. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 172 and a light chain (LC) variable domain comprising SEQ ID NO: 176. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 172 and a light chain (LC) variable domain comprising SEQ ID NO: 177. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 172 and a light chain (LC) variable domain comprising SEQ ID NO: 178.

[0162] In some embodiments, the anti-TL1A antibody comprises a HCDR1 comprising SEQ ID NO: 162, a HCDR2 comprising SEQ ID NO: 164, a HCDR3 comprising SEQ ID NO: 165, a LCDR1 comprising SEQ ID NO: 168, a LCDR2 comprising SEQ ID NO: 169, and a LCDR3 comprising SEQ ID NO: 170. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 172 and a light chain (LC) variable domain comprising SEQ ID NO: 179. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 172 and a light chain (LC) variable domain comprising SEQ ID NO: 180. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 172 and a light chain (LC) variable domain comprising SEQ ID NO: 181. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 172 and a light chain (LC) variable domain comprising SEQ ID NO: 182.

[0163] In some embodiments, the anti-TL1A antibody comprises a HCDR1 comprising SEQ ID NO: 163, a HCDR2 comprising SEQ ID NO: 164, a HCDR3 comprising SEQ ID NO: 166, a LCDRI1 comprising SEQ ID NO: 167, a LCDR2 comprising SEQ ID NO: 169, and a LCDR3 comprising SEQ ID NO: 170. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 173 and a light chain (LC) variable domain comprising SEQ ID NO: 175. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 173 and a light chain (LC) variable domain comprising SEQ ID NO: 176. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 173 and a light chain (LC) variable domain comprising SEQ ID NO: 177. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 173 and a light chain (LC) variable domain comprising SEQ ID NO: 178. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 173 and a light chain (LC) variable domain comprising SEQ ID NO: 179. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 173 and a light chain (LC) variable domain comprising SEQ ID NO: 180. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 173 and a light chain (LC) variable domain comprising SEQ ID NO: 181. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 173 and a light chain (LC) variable domain comprising SEQ ID NO: 182.

[0164] In some embodiments, the anti-TL1A antibody comprises a HCDR1 comprising SEQ ID NO: 163, a HCDR2 comprising SEQ ID NO: 164, a HCDR3 comprising SEQ ID NO: 166, a LCDR1 comprising SEQ ID NO: 168, a LCDR2 comprising SEQ ID NO: 169, and a LCDR3 comprising SEQ ID NO: 170. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 174 and a light chain (LC) variable domain comprising SEQ ID NO: 179. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 174 and a light chain (LC) variable domain comprising SEQ ID NO: 180. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 174 and a light chain (LC) variable domain comprising SEQ ID NO: 181. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 174 and a light chain (LC) variable domain comprising SEQ ID NO: 182. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 174 and a light chain (LC) variable domain comprising SEQ ID NO: 175. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 174 and a light chain (LC) variable domain comprising SEQ ID NO: 176. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 174 and a light chain (LC) variable domain comprising SEQ ID NO: 177. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 174 and a light chain (LC) variable domain comprising SEQ ID NO: 178.

[0165] In some embodiments, the anti-TL1A antibody comprises a HCDR1 comprising SEQ ID NO: 183, a HCDR2 comprising SEQ ID NO: 184, a HCDR3 comprising SEQ ID NO: 185, a LCDRI1 comprising SEQ ID NO: 186, a LCDR2 comprising SEQ ID NO: 187, and a LCDR3 comprising SEQ ID NO: 188. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 189 and a light chain (LC) variable domain comprising SEQ ID NO: 194. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 189 and a light chain (LC) variable domain comprising SEQ ID NO: 195. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 189 and a light chain (LC) variable domain comprising SEQ ID NO: 196. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 189 and a light chain (LC) variable domain comprising SEQ ID NO: 197. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 190 and a light chain (LC) variable domain comprising SEQ ID NO: 194. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 190 and a light chain (LC) variable domain comprising SEQ ID NO: 195. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 190 and a light chain (LC) variable domain comprising SEQ ID NO: 196. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 190 and a light chain (LC) variable domain comprising SEQ ID NO: 197. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 191 and a light chain (LC) variable domain comprising SEQ ID NO: 194. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 191 and a light chain (LC) variable domain comprising SEQ ID NO: 195. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 191 and a light chain (LC) variable domain comprising SEQ ID NO: 196. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 191 and a light chain (LC) variable domain comprising SEQ ID NO: 197. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 192 and a light chain (LC) variable domain comprising SEQ ID NO: 194. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 192 and a light chain (LC) variable domain comprising SEQ ID NO: 195. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 192 and a light chain (LC) variable domain comprising SEQ ID NO: 196. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 192 and a light chain (LC) variable domain comprising SEQ ID NO: 197. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 193 and a light chain (LC) variable domain comprising SEQ ID NO: 194. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 193 and a light chain (LC) variable domain comprising SEQ ID NO: 195. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 193 and a light chain (LC) variable domain comprising SEQ ID NO: 196. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 193 and a light chain (LC) variable domain comprising SEQ ID NO: 197.

[0166] In some embodiments, the anti-TL1A antibody comprises a HCDR1 comprising SEQ ID NO: 198, a HCDR2 comprising SEQ ID NO: 199, a HCDR3 comprising SEQ ID NO: 200, a LCDRI1 comprising SEQ ID NO: 201, a LCDR2 comprising SEQ ID NO: 202, and a LCDR3 comprising SEQ ID NO: 203. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 204 and a light chain (LC) variable domain comprising SEQ ID NO: 205. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 206 and a light chain (LC) variable domain comprising SEQ ID NO: 207. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 208 and a light chain (LC) variable domain comprising SEQ ID NO: 209. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 210 and a light chain (LC) variable domain comprising SEQ ID NO: 211. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 212 and a light chain (LC) variable domain comprising SEQ ID NO: 213. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 214 and a light chain (LC) variable domain comprising SEQ ID NO: 215. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 216 and a light chain (LC) variable domain comprising SEQ ID NO: 217. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 218 and a light chain (LC) variable domain comprising SEQ ID NO: 219. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 220 and a light chain (LC) variable domain comprising SEQ ID NO: 221. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 222 and a light chain (LC) variable domain comprising SEQ ID NO: 223. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 224 and a light chain (LC) variable domain comprising SEQ ID NO: 225. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 226 and a light chain (LC) variable domain comprising SEQ ID NO: 227.

[0167] In some embodiments, the anti-TL1A antibody comprises a HCDR1 comprising SEQ ID NO: 228, a HCDR2 comprising SEQ ID NO: 229, a HCDR3 comprising SEQ ID NO: 230, a LCDR1 comprising SEQ ID NO: 231, a LCDR2 comprising SEQ ID NO: 232, and a LCDR3 comprising SEQ ID NO: 233. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 234 and a light chain (LC) variable domain comprising SEQ ID NO: 235.

[0168] In some embodiments, the anti-TL1A antibody comprises a HCDR1 comprising SEQ ID NO: 236, a HCDR2 comprising SEQ ID NO: 237, a HCDR3 comprising SEQ ID NO: 238, a LCDRI1 comprising SEQ ID NO: 239, a LCDR2 comprising SEQ ID NO: 240, and a LCDR3 comprising SEQ ID NO: 241. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 242 and a light chain (LC) variable domain comprising SEQ ID NO: 243.

[0169] In some embodiments, the anti-TL1A antibody comprises a HCDR1 comprising SEQ ID NO: 246, a HCDR2 comprising SEQ ID NO: 247, a HCDR3 comprising SEQ ID NO: 248, a LCDRI1 comprising SEQ ID NO: 249, a LCDR2 comprising SEQ ID NO: 250, and a LCDR3 comprising SEQ ID NO: 251. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 244 and a light chain (LC) variable domain comprising SEQ ID NO: 245. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 252 and a light chain (LC) variable domain comprising SEQ ID NO: 253. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 254 and a light chain (LC) variable domain comprising SEQ ID NO: 255. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 256 and a light chain (LC) variable domain comprising SEQ ID NO: 257.

[0170] In some embodiments, the anti-TL1A antibody comprises a HCDR1 comprising SEQ ID NO: 276, a HCDR2 comprising SEQ ID NO: 277, a HCDR3 comprising SEQ ID NO: 278, a LCDR1 comprising SEQ ID NO: 279, a LCDR2 comprising SEQ ID NO: 280, and a LCDR3 comprising SEQ ID NO: 281. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 282 and a light chain (LC) variable domain comprising SEQ ID NO: 283.

[0171] In some embodiments, the anti-TL1A antibody comprises a HCDR1 comprising SEQ ID NO: 284, a HCDR2 comprising SEQ ID NO: 285, a HCDR3 comprising SEQ ID NO: 286, a LCDRI1 comprising SEQ ID NO: 287, a LCDR2 comprising SEQ ID NO: 288, and a LCDR3 comprising SEQ ID NO: 299. In some cases, the anti-TL1A antibody comprises a heavy chain (HC) variable domain comprising SEQ ID NO: 290 and a light chain (LC) variable domain comprising SEQ ID NO: 291.

[0172] In some embodiments, the anti-TL1A antibody is A100. In some embodiments, the anti-TL1A antibody is A101. In some embodiments, the anti-TL1A antibody is A102. In some embodiments, the anti-TL1A antibody is A103. In some embodiments, the anti-TL1A antibody is A104. In some embodiments, the anti-TL1A antibody is A105. In some embodiments, the anti- TL1A antibody is A106. In some embodiments, the anti-TL1A antibody is A107. In some embodiments, the anti-TL1A antibody is A108. In some embodiments, the anti-TL1A antibody is A109. In some embodiments, the anti-TL1A antibody is A110. In some embodiments, the anti- TL1A antibody is A111. In some embodiments, the anti-TL1A antibody is A112. In some embodiments, the anti-TL1A antibody is A113. In some embodiments, the anti-TL1A antibody is A114. In some embodiments, the anti-TL1A antibody is A115. In some embodiments, the anti- TL1A antibody is A116. In some embodiments, the anti-TL1A antibody is A117. In some embodiments, the anti-TL1A antibody is A118. In some embodiments, the anti-TL1A antibody is A119. In some embodiments, the anti-TL1A antibody is A120. In some embodiments, the anti- TL1A antibody is A121. In some embodiments, the anti-TL1A antibody is A122. In some embodiments, the anti-TL1A antibody is A123. In some embodiments, the anti-TL1A antibody is A124. In some embodiments, the anti-TL1A antibody is A125. In some embodiments, the anti- TL1A antibody is A126. In some embodiments, the anti-TL1A antibody is A127. In some embodiments, the anti-TL1A antibody is A128. In some embodiments, the anti-TL1A antibody is A129. In some embodiments, the anti-TL1A antibody is A130. In some embodiments, the anti- TL1A antibody is A131. In some embodiments, the anti-TL1A antibody is A132. In some embodiments, the anti-TL1A antibody is A133. In some embodiments, the anti-TL1A antibody is A134. In some embodiments, the anti-TL1A antibody is A135. In some embodiments, the anti- TL1A antibody is A136. In some embodiments, the anti-TL1A antibody is A137. In some embodiments, the anti-TL1A antibody is A138. In some embodiments, the anti-TL1A antibody is A139. In some embodiments, the anti-TL1A antibody is A140. In some embodiments, the anti- TL1A antibody is A141. In some embodiments, the anti-TL1A antibody is A142. In some embodiments, the anti-TL1A antibody is A143. In some embodiments, the anti-TL1A antibody is A144. In some embodiments, the anti-TL1A antibody is A145. In some embodiments, the anti- TL1A antibody is A146. In some embodiments, the anti-TL1A antibody is A147. In some embodiments, the anti-TL1A antibody is A148. In some embodiments, the anti-TL1A antibody is A149. In some embodiments, the anti-TL1A antibody is A150. In some embodiments, the anti- TL1A antibody is A151. In some embodiments, the anti-TL1A antibody is A152. In some embodiments, the anti-TL1A antibody is A153. In some embodiments, the anti-TL1A antibody is A154. In some embodiments, the anti-TL1A antibody is A155. In some embodiments, the anti- TL1A antibody is A156. In some embodiments, the anti-TL1A antibody is A157. In some embodiments, the anti-TL1A antibody is A158. In some embodiments, the anti-TL1A antibody is A159. In some embodiments, the anti-TL1A antibody is A160. In some embodiments, the anti- TL1A antibody is A161. In some embodiments, the anti-TL1A antibody is A162. In some embodiments, the anti-TL1A antibody is A163. In some embodiments, the anti-TL1A antibody is A164. In some embodiments, the anti-TL1A antibody is A165. In some embodiments, the anti- TL1A antibody is A166. In some embodiments, the anti-TL1A antibody is A167. In some embodiments, the anti-TL1A antibody is A168. In some embodiments, the anti-TL1A antibody is A169. In some embodiments, the anti-TL1A antibody is A170. In some embodiments, the anti- TL1A antibody is A171. In some embodiments, the anti-TL1A antibody is A172. In some embodiments, the anti-TL1A antibody is A173. In some embodiments, the anti-TL1A antibody is A174. In some embodiments, the anti-TL1A antibody is A175. In some embodiments, the anti- TL1A antibody is A176. In some embodiments, the anti-TL1A antibody is A177.

[0173] In some embodiments, the anti-DR3 is A178. In some embodiments, the anti-DR3 is A179. In some embodiments, the anti-DR3 is A180. In some embodiments, the anti-DR3 is A181. In some embodiments, the anti-DR3 is A182. In some embodiments, the anti-DR3 is A183. In some embodiments, the anti-DR3 is A184. In some embodiments, the anti-DR3 is A185. In some embodiments, the anti-DR3 is A186. In some embodiments, the anti-DR3 is A187. In some embodiments, the anti-DR3 is A188. In some embodiments, the anti-DR3 is A189. In some embodiments, the anti-DR3 is A190. In some embodiments, the anti-DR3 is A191. In some embodiments, the anti-DR3 is A192. In some embodiments, the anti-DR3 is A193. In some embodiments, the anti-DR3 is A194. In some embodiments, the anti-DR3 is A195. In some embodiments, the anti-DR3 is A196. In some embodiments, the anti-DR3 is A197. In some embodiments, the anti-DR3 is A198. In some embodiments, the anti-DR3 is A199. In some embodiments, the anti-DR3 is A200. In some embodiments, the anti-DR3 is A201. In some embodiments, the anti-DR3 is A202. In some embodiments, the anti-DR3 is A203. In some embodiments, the anti-DR3 is A204. In some embodiments, the anti-DR3 is A205. In some embodiments, the anti-DR3 is A206. In some embodiments, the anti-DR3 is A207. In some embodiments, the anti-DR3 is A208. In some embodiments, the anti-DR3 is A209. In some embodiments, the anti-DR3 is A210. In some embodiments, the anti-DR3 is A211. In some embodiments, the anti-DR3 is A212. In some embodiments, the anti-DR3 is A213. In some embodiments, the anti-DR3 is A214. In some embodiments, the anti-DR3 is A215. In some embodiments, the anti-DR3 is A216. In some embodiments, the anti-DR3 is A217. In some embodiments, the anti-DR3 is A218. In some embodiments, the anti-DR3 is A219. In some embodiments, the anti-DR3 is A220. In some embodiments, the anti-DR3 is A221. In some embodiments, the anti-DR3 is A222. In some embodiments, the anti-DR3 is A223. In some embodiments, the anti-DR3 is A224. In some embodiments, the anti-DR3 is A225. In some embodiments, the anti-DR3 is A226. In some embodiments, the anti-DR3 is A227. In some embodiments, the anti-DR3 is A228. In some embodiments, the anti-DR3 is A229. In some embodiments, the anti-DR3 is A230. In some embodiments, the anti-DR3 is A231. In some embodiments, the anti-DR3 is A232. In some embodiments, the anti-DR3 is A233. In some embodiments, the anti-DR3 is A234. In some embodiments, the anti-DR3 is A235. In some embodiments, the anti-DR3 is A236. In some embodiments, the anti-DR3 is A237. In some embodiments, the anti-DR3 is A238. In some embodiments, the anti-DR3 is A239. In some embodiments, the anti-DR3 is A240. In some embodiments, the anti-DR3 is A241. In some embodiments, the anti-DR3 is A242.

[0174] In some cases, the anti-TL1A antibody binds to at least one or more of the same residues of human TL1A as an antibody described herein. For example, the anti-TL1A antibody binds to at least one or more of the same residues of human TL1A as an antibody selected from A100-A177. In some cases, the anti-TL1A antibody binds to the same epitope of human TL1A as an antibody selected from A100-A177. In some cases, the anti-TL1A antibody binds to the same region of human TL1A as an antibody selected from A100-A177.

[0175] In some embodiments, the anti-TL1A antibody comprises any one of the following embodiments 1-547 below. 1. An antibody or antigen-binding fragment that specifically binds to TL1A, comprising: a heavy chain variable region comprising four heavy chain framework regions (HFR 1, HFR2, HFR3, and HFR4), and three heavy chain complementarity-determining regions (HCDRI1, HCDR2, and HCDR3), the heavy chain variable region comprising: (a) a HFR1 selected from: (i) a HFR1 comprising SEQ ID NO: 100100, (ii) a HFR1 comprising SEQ ID NO: 100108, and (iii) a HFR1 comprising an amino acid sequence that differs from a sequence selected from the group consisting of SEQ ID NOS: 100100 and 100108 by up to five, four, three, or two amino acids, a HFR2 selected from: (i) a HFR2 comprising SEQ ID NO: 100101, and (ii) a HFR2 comprising an amino acid sequence that differs from SEQ ID NO: 100101 by up to five, four, three, or two amino acids, a HFR3 selected from: (i) a HFR3 comprising SEQ ID NO: 100102, (ii) a HFR3 comprising SEQ ID NO: 100109, and (iii) a HFR3 comprising an amino acid sequence that differs from a sequence selected from the group consisting of SEQ ID NOS: 100102 and 100109 by up to five, four, three, or two amino acids, a HFR4 selected from: (i) a HFR4 comprising SEQ ID NO: 100103, and (ii) a HFR4 comprising an amino acid sequence that differs from SEQ ID NO: 100103 by up to five, four, three, or two amino acids, a HCDRI1 selected from: (i) a HCDR1 comprising SEQ ID NO: 1009, (ii) a HCDRI comprising SEQ ID NO: 100150, wherein Xi is selected from D and E, Xa is selected from I, P and V, X; is selected from G, Q, S, and V, Xu is selected from F and Y, and Xs is selected from I and M, (iii) a HCDR1 selected from SEQ ID NOS: 100200-100295, and (iv) a HCDR1 comprising an amino acid sequence that differs from a sequence selected from the group consisting of SEQ ID NOS: 1009, 100150 and 100200-100295 by up to five, four, three, or two amino acids, a HCDR2 selected from: (i) a HCDR2 comprising SEQ ID NO: 10012, and (ii) a HCDR2 comprising an amino acid sequence that differs from SEQ ID NO: 10012 by up to five, four, three, or two amino acids, and a HCDR3 selected from (i) a HCDR3 comprising SEQ ID NO: 10015, (ii) a HCDR3 comprising SEQ ID NO: 100152, wherein X is selected from L and M, and X3 is selected from E, LK, L,M, Q, T, V, W, and Y, (iii) a HCDR3 selected from SEQ ID NOS: 100296-100314, and (iv) a HCDR3 comprising an amino acid sequence that differs from a sequence selected from the group consisting of SEQ ID NOS: 10015, 100152 and 100296-100314 by up to five, four, three, or two amino acids; and a light chain variable region comprising four light chain framework regions (LFR1, LFR2, LFR3, and LFR4), and three light chain complementarity-determining regions (LCDR1, LCDR2, and LCDR3), the light chain variable region comprising: (a) a LFR1 selected from: (i) a LFR1 comprising SEQ ID NO: 100104, and (ii) a LFR1 comprising an amino acid sequence that differs from SEQ ID NO: 100104 by up to five, four, three, or two amino acids, (b) a LFR2 selected from: (i) a LFR2 comprising SEQ ID NO: 100105, and (ii) a LFR2 comprising an amino acid sequence that differs from SEQ ID NO: 100105 by up to five, four, three, or two amino acids, (c) a LFR3 selected from: (i) a LFR3 comprising SEQ ID NO: 100106, (ii) a LFR3 comprising SEQ ID NO: 100110, and (iii) a LFR3 comprising an amino acid sequence that differs from a sequence selected from the group consisting of SEQ ID NOS: 100106 and 100110 by up to five, four, three, or two amino acids, (d) a LFR4 selected from: (i) a LFR4 comprising SEQ ID NO: 100107, and (ii) a LFR4 comprising an amino acid sequence that differs from SEQ ID NO: 100107 by up to five, four, three, or two amino acids, (e) a LCDRI selected from: (i) a LCDR1 comprising SEQ ID NO: 10018, and (ii) a LCDRI comprising an amino acid sequence that differs from SEQ ID NO: 10018 by up to five, four, three, or two amino acids, (f) a LCDR2 selected from: (i) a LCDR2 comprising SEQ ID NO: 10021, and (ii) a LCDR2 comprising an amino acid sequence that differs from SEQ ID NO: 10021 by up to five, four, three, or two amino acids, and (g) a LCDR3 selected from (i) a LCDR3 comprising SEQ ID NO: 10024, (ii) a LCDR3 comprising SEQ ID NO: 100155, wherein Xi is selected from Q and N, X; is selected from D, E, H, N, Q, and S, X; is selected from A and G, and Xs is selected from D, F, K, N, R, S, and T, (iii) a LCDR3 selected from SEQ ID NOS: 100315-100482, and (iv) a LCDR3 comprising an amino acid sequence that differs from a sequence selected from the group consisting of SEQ ID NOS: 10024, 100155, and 100315-100482 by up to five, four, three, or two amino acids. 2. The antibody or antigen-binding fragment of embodiment 1, provided that the HFR1 comprises SEQ ID NO: 100100. 3. The antibody or antigen-binding fragment of embodiment 1, provided that the HFR1 comprises SEQ ID NO: 100108. 4. The antibody or antigen-binding fragment of embodiment 1, provided that the HFR1 comprises an amino acid sequence that differs from SEQ ID NO: 100100 by up to five, four, three, or two amino acids. 5. The antibody or antigen-binding fragment of embodiment 1, provided that the HFR1 comprises an amino acid sequence that differs from SEQ ID NO: 100108 by up to five, four, three, or two amino acids. 6. The antibody or antigen-binding fragment of any of embodiments 1-5, provided that the HFR2 comprises SEQ ID NO: 100101. 7. The antibody or antigen-binding fragment of any of embodiments 1-5, provided that the HFR2 comprises an amino acid sequence that differs from SEQ ID NO: 100101 by up to five, four, three, or two amino acids. 8. The antibody or antigen-binding fragment of any of embodiments 1-7, provided that the HFR3 comprises SEQ ID NO: 100102. 9. The antibody or antigen-binding fragment of any of embodiments 1-7, provided that the HFR3 comprises SEQ ID NO: 100109. 10. The antibody or antigen-binding fragment of any of embodiments 1-7, provided that the HFR3 comprises an amino acid sequence that differs from SEQ ID NO: 100102 by up to five, four, three, or two amino acids. 11. The antibody or antigen-binding fragment of any of embodiments 1-7, provided that the HFR3 comprises an amino acid sequence that differs from SEQ ID NO: 100109 by up to five, four, three, or two amino acids. 12. The antibody or antigen-binding fragment of any of embodiments 1-11, provided that the HFR4 comprises SEQ ID NO: 100103. 13. The antibody or antigen-binding fragment of any of embodiments 1-11, provided that the HFR4 comprises an amino acid sequence that differs from SEQ ID NO: 100103 by up to five, four, three, or two amino acids. 14. The antibody or antigen-binding fragment of any of embodiments 1-13, provided that the HCDRI1 comprises SEQ ID NO: 1009. 15. The antibody or antigen-binding fragment of any of embodiments 1-13, provided that the HCDRI1 comprises SEQ ID NO: 100150. 16. The antibody or antigen-binding fragment of embodiment 15, provided that Xj is E. 17. The antibody or antigen-binding fragment of embodiment 15 or embodiment 16, provided that X; is selected from P and V. 18. The antibody or antigen-binding fragment of any of embodiments 15-17, provided that X3 is selected from G, S, and V. 19. The antibody or antigen-binding fragment of any of embodiments 15-18, provided that Xu is F. 20. The antibody or antigen-binding fragment of any of embodiments 15-19, provided that Xs is L 21. The antibody or antigen-binding fragment of any of embodiments 1-13, provided that the HCDR1 comprises an amino acid sequence selected from SEQ ID NOS: 100200-100295. 22. The antibody or antigen-binding fragment of any of embodiments 1-21, provided that the HCDR2 comprises SEQ ID NO: 10012. 23. The antibody or antigen-binding fragment of any of embodiments 1-21, provided that the HCDR2 comprises an amino acid sequence that differs from SEQ ID NO: 10012 by up to five, four, three, or two amino acids. 24. The antibody or antigen-binding fragment of any of embodiments 1-23, provided that the HCDR3 comprises SEQ ID NO: 10015. 25. The antibody or antigen-binding fragment of any of embodiments 1-23, provided that the HCDR3 comprises SEQ ID NO: 100152. 26. The antibody or antigen-binding fragment of embodiment 25, provided that Xi is M. 27. The antibody or antigen-binding fragment of embodiment 25 or embodiment 26, provided that Xz is selected from E, L K,L. M, Q, T, W, and Y. 28. The antibody or antigen-binding fragment of any of embodiments 1-23, provided that the HCDR3 comprises a sequence selected from SEQ ID NOS: 100296-100314. 29. The antibody or antigen-binding fragment of any of embodiments 1-28, provided that the LFR1 comprises SEQ ID NO: 100104, 30. The antibody or antigen-binding fragment of any of embodiments 1-28, provided that the LFR1 comprises an amino acid sequence that differs from SEQ ID NO: 100104 by up to five, four, three, or two amino acids. 31. The antibody or antigen-binding fragment of any of embodiments 1-30, provided that the LFR2 comprises SEQ ID NO: 100105. 32. The antibody or antigen-binding fragment of any of embodiments 1-30, provided that the LFR2 comprises an amino acid sequence that differs from SEQ ID NO: 100105 by up to five, four, three, or two amino acids. 33. The antibody or antigen-binding fragment of any of embodiments 1-32, provided that the LFR3 comprises SEQ ID NO: 100106. 34. The antibody or antigen-binding fragment of any of embodiments 1-32, provided that the LFR3 comprises SEQ ID NO: 100110. 35. The antibody or antigen-binding fragment of any of embodiments 1-32, provided that the LFR3 comprises an amino acid sequence that differs from SEQ ID NO: 100106 by up to five, four, three, or two amino acids. 36. The antibody or antigen-binding fragment of any of embodiments 1-32, provided that the LFR3 comprises an amino acid sequence that differs from SEQ ID NO: 100110 by up to five, four, three, or two amino acids. 37. The antibody or antigen-binding fragment of any of embodiments 1-36, provided that the LFR4 comprises SEQ ID NO: 100107. 38. The antibody or antigen-binding fragment of any of embodiments 1-36, provided that the LFR4 comprises an amino acid sequence that differs from SEQ ID NO: 100107 by up to five, four, three, or two amino acids. 39. The antibody or antigen-binding fragment of any of embodiments 1-38, provided that the LCDRI1 comprises SEQ ID NO: 10018. 40. The antibody or antigen-binding fragment of any of embodiments 1-38, provided that the LCDRI1 comprises an amino acid sequence that differs from SEQ ID NO: 10018 by up to five, four, three, or two amino acids. 41. The antibody or antigen-binding fragment of any of embodiments 1-40, provided that the LCDR2 comprises SEQ ID NO: 10021. 42. The antibody or antigen-binding fragment of any of embodiments 1-40, provided that the LCDR2 comprises an amino acid sequence that differs from SEQ ID NO: 10021 by up to five, four, three, or two amino acids. 43. The antibody or antigen-binding fragment of any of embodiments 1-42, provided that the LCDR3 comprises SEQ ID NO: 10024. 44. The antibody or antigen-binding fragment of any of embodiments 1-42, provided that the LCDR3 comprises SEQ ID NO: 100155. 45. The antibody or antigen-binding fragment of embodiment 44, provided that X is N. 46. The antibody or antigen-binding fragment of embodiment 44 or embodiment 45, provided that X3 is selected from D, E, H, N, and Q. 47. The antibody or antigen-binding fragment of any of embodiments 44-46, provided that Xs is A. 48. The antibody or antigen-binding fragment of any of embodiments 44-47, provided that Xs is selected from D,F, K, R, S, and T. 49. The antibody or antigen-binding fragment of any of embodiments 1-42, provided that the LCDR3 comprises an amino acid sequence selected from SEQ ID NOS: 100315-100482. 50. The antibody or antigen-binding fragment of embodiment 1, provided that the HFR 1 comprises SEQ ID NO: 100100, the HFR2 comprises SEQ ID NO: 100101, the HFR3 comprises SEQ ID NO: 100102, the HFR4 comprises SEQ ID NO: 100103, the LFRI comprises SEQ ID NO: 100104, the LFR2 comprises SEQ ID NO: 100105, the LFR3 comprises SEQ ID NO: 100106, and the LFR4 comprises SEQ ID NO: 100107. 51. The antibody or antigen-binding fragment of embodiment 1, provided that the HFR1 comprises SEQ ID NO: 100108, the HFR2 comprises SEQ ID NO: 100101, the HFR3 comprises SEQ ID NO: 100109, the HFR4 comprises SEQ ID NO: 100103, the LFRI comprises SEQ ID NO: 100104, the LFR2 comprises SEQ ID NO: 100105, the LFR3 comprises SEQ ID NO: 100110, and the LFR4 comprises SEQ ID NO: 100107. 52. The antibody or antigen-binding fragment of embodiment 1, provided that the HFR 1 comprises SEQ ID NO: 100108, the HFR2 comprises SEQ ID NO: 100101, the HFR3 comprises SEQ ID NO: 100109, the HFR4 comprises SEQ ID NO: 100103, the LFRI comprises SEQ ID NO: 100104, the LFR2 comprises SEQ ID NO: 100105, the LFR3 comprises SEQ ID NO: 100106, and the LFR4 comprises SEQ ID NO: 100107. 53. The antibody or antigen-binding fragment of any of embodiments 1 and 50-52, provided that the HCDR1 comprises SEQ ID NO: 1009, the HCDR2 comprises SEQ ID NO: 10012, the HCDR3 comprises SEQ ID NO: 10015, the LCDR1 comprises SEQ ID NO: 10018, the LCDR2 comprises SEQ ID NO: 10021, and the LCDR3 comprises SEQ ID NO: 10024. 54. The antibody or antigen-binding fragment of any of embodiments 1 and 50-52, provided that the HCDR1 comprises SEQ ID NO: 100150, the HCDR2 comprises SEQ ID NO: 10012, the HCDR3 comprises SEQ ID NO: 100152, the LCDR 1 comprises SEQ ID NO: 10018, the LCDR2 comprises SEQ ID NO: 10021, and the LCDR3 comprises SEQ ID NO: 100155. 55. The antibody or antigen-binding fragment of embodiment 1, provided that the HFR 1 comprises SEQ ID NO: 100100, the HFR2 comprises SEQ ID NO: 100101, the HFR3 comprises SEQ ID NO: 100102, the HFR4 comprises SEQ ID NO: 100103, the LFRI comprises SEQ ID NO: 100104, the LFR2 comprises SEQ ID NO: 100105, the LFR3 comprises SEQ ID NO: 100106, the LFR4 comprises SEQ ID NO: 100107, the HCDR1 comprises SEQ ID NO: 1009, the HCDR2 comprises SEQ ID NO: 10012, the HCDR3 comprises SEQ ID NO: 10015, the LCDR1 comprises SEQ ID NO: 10018, the LCDR2 comprises SEQ ID NO: 10021, and the LCDR3 comprises SEQ ID NO: 10024. 56. The antibody or antigen-binding fragment of embodiment 1, provided that the HFR1 comprises SEQ ID NO: 100100, the HFR2 comprises SEQ ID NO: 100101, the HFR3 comprises SEQ ID NO: 100102, the HFR4 comprises SEQ ID NO: 100103, the LFRI comprises SEQ ID NO: 100104, the LFR2 comprises SEQ ID NO: 100105, the LFR3 comprises SEQ ID NO: 100106, the LFR4 comprises SEQ ID NO: 100107, the HCDR1 comprises SEQ ID NO: 100150, the HCDR2 comprises SEQ ID NO: 10012, the HCDR3 comprises SEQ ID NO: 100152, the LCDR1 comprises SEQ ID NO: 10018, the LCDR2 comprises SEQ ID NO: 10021, and the LCDR3 comprises SEQ ID NO: 100155. 57. The antibody or antigen-binding fragment of embodiment 1, provided that the HFR1 comprises SEQ ID NO: 100108, the HFR2 comprises SEQ ID NO: 100101, the HFR3 comprises SEQ ID NO: 100109, the HFR4 comprises SEQ ID NO: 100103, the LFRI comprises SEQ ID NO: 100104, the LFR2 comprises SEQ ID NO: 100105, the LFR3 comprises SEQ ID NO: 100110, the LFR4 comprises SEQ ID NO: 100107, the HCDR1 comprises SEQ ID NO: 1009, the HCDR2 comprises SEQ ID NO: 10012, the HCDR3 comprises SEQ ID NO: 10015, the LCDR1 comprises SEQ ID NO: 10018, the LCDR2 comprises SEQ ID NO: 10021, and the LCDR3 comprises SEQ ID NO: 10024. 58. The antibody or antigen-binding fragment of embodiment 1, provided that the HFR1 comprises SEQ ID NO: 100108, the HFR2 comprises SEQ ID NO: 100101, the HFR3 comprises SEQ ID NO: 100109, the HFR4 comprises SEQ ID NO: 100103, the LFRI comprises SEQ ID NO: 100104, the LFR2 comprises SEQ ID NO: 100105, the LFR3 comprises SEQ ID NO: 100110, the LFR4 comprises SEQ ID NO: 100107, the HCDR1 comprises SEQ ID NO: 100150, the HCDR2 comprises SEQ ID NO: 10012, the HCDR3 comprises SEQ ID NO: 100152, the LCDR 1 comprises SEQ ID NO: 10018, the LCDR2 comprises SEQ ID NO: 10021, and the LCDR3 comprises SEQ ID NO: 100155. 59. The antibody or antigen-binding fragment of embodiment 1, provided that the HFR1 comprises SEQ ID NO: 100108, the HFR2 comprises SEQ ID NO: 100101, the HFR3 comprises SEQ ID NO: 100109, the HFR4 comprises SEQ ID NO: 100103, the LFRI comprises SEQ ID NO: 100104, the LFR2 comprises SEQ ID NO: 100105, the LFR3 comprises SEQ ID NO: 100106, the LFR4 comprises SEQ ID NO: 100107, the HCDR1 comprises SEQ ID NO: 1009, the HCDR2 comprises SEQ ID NO: 10012, the HCDR3 comprises SEQ ID NO: 10015, the LCDR1 comprises SEQ ID NO: 10018, the LCDR2 comprises SEQ ID NO: 10021, and the LCDR3 comprises SEQ ID NO: 10024. 60. The antibody or antigen-binding fragment of embodiment 1, provided that the HFR1 comprises SEQ ID NO: 100108, the HFR2 comprises SEQ ID NO: 100101, the HFR3 comprises SEQ ID NO: 100109, the HFR4 comprises SEQ ID NO: 100103, the LFRI comprises SEQ ID NO: 100104, the LFR2 comprises SEQ ID NO: 100105, the LFR3 comprises SEQ ID NO: 100106, the LFR4 comprises SEQ ID NO: 100107, the HCDR1 comprises SEQ ID NO: 100150, the HCDR2 comprises SEQ ID NO: 10012, the HCDR3 comprises SEQ ID NO: 100152, the LCDR1 comprises SEQ ID NO: 10018, the LCDR2 comprises SEQ ID NO: 10021, and the LCDR3 comprises SEQ ID NO: 100155. 61. The antibody or antigen-binding fragment of any of embodiments 1, 54, 56, 58, and 60, provided that the X; of SEQ ID NO: 100150 is D. 62. The antibody or antigen-binding fragment of any of embodiments 1, 54, 56, 58, and 60, provided that the X; of SEQ ID NO: 100150 is E. 63. The antibody or antigen-binding fragment of any of embodiments 1, 54, 56, 58, and 60- 62, provided that the X; of SEQ ID NO: 100150 is I. 64. The antibody or antigen-binding fragment of any of embodiments 1, 54, 56, 58, and 60- 62, provided that the X; of SEQ ID NO: 100150 is P. 65. The antibody or antigen-binding fragment of any of embodiments 1, 54, 56, 58, and 60- 62, provided that the X; of SEQ ID NO: 100150is V. 66. The antibody or antigen-binding fragment of any of embodiments 1, 54, 56, 58, and 60- 65, provided that the X; of SEQ ID NO: 100150 is G. 67. The antibody or antigen-binding fragment of any of embodiments 1, 54, 56, 58, and 60- 65, provided that the X; of SEQ ID NO: 100150 is Q. 68. The antibody or antigen-binding fragment of any of embodiments 1, 54, 56, 58, and 60- 65, provided that the X; of SEQ ID NO: 100150 is S. 69. The antibody or antigen-binding fragment of any of embodiments 1, 54, 56, 58, and 60- 65, provided that the X; of SEQ ID NO: 100150is V. 70. The antibody or antigen-binding fragment of any of embodiments 1, 54, 56, 58, and 60- 69, provided that the Xs of SEQ ID NO: 100150 is F. 71. The antibody or antigen-binding fragment of any of embodiments 1, 54, 56, 58, and 60- 69, provided that the Xs of SEQ ID NO: 100150is Y. 72. The antibody or antigen-binding fragment of any of embodiments 1, 54, 56, 58, and 60- 71, provided that the Xs of SEQ ID NO: 100150 is L 73. The antibody or antigen-binding fragment of any of embodiments 1, 54, 56, 58, and 60- 71, provided that the Xs of SEQ ID NO: 100150 is M. 74. The antibody or antigen-binding fragment of any of embodiments 1, 54, 56, 58, and 60- 73, provided that the Xj of SEQ ID NO: 100152 is L. 75. The antibody or antigen-binding fragment of any of embodiments 1, 54, 56, 58, and 60- 73, provided that the X; of SEQ ID NO: 100152 is M. 76. The antibody or antigen-binding fragment of any of embodiments 1, 54, 56, 58, and 60- 75, provided that the X; of SEQ ID NO: 100152 is E. 77. The antibody or antigen-binding fragment of any of embodiments 1, 54, 56, 58, and 60- 75, provided that the X; of SEQ ID NO: 100152 is L 78. The antibody or antigen-binding fragment of any of embodiments 1, 54, 56, 58, and 60- 75, provided that the X; of SEQ ID NO: 100152 is K. 79. The antibody or antigen-binding fragment of any of embodiments 1, 54, 56, 58, and 60- 75, provided that the X; of SEQ ID NO: 100152 is L. 80. The antibody or antigen-binding fragment of any of embodiments 1, 54, 56, 58, and 60- 75, provided that the Xz of SEQ ID NO: 100152 is M. 81. The antibody or antigen-binding fragment of any of embodiments 1, 54, 56, 58, and 60- 75, provided that the X; of SEQ ID NO: 100152 is Q. 82. The antibody or antigen-binding fragment of any of embodiments 1, 54, 56, 58, and 60- 75, provided that the X; of SEQ ID NO: 100152 is T. 83. The antibody or antigen-binding fragment of any of embodiments 1, 54, 56, 58, and 60- 75, provided that the Xz of SEQ ID NO: 100152 is V. 84. The antibody or antigen-binding fragment of any of embodiments 1, 54, 56, 58, and 60- 75, provided that the X; of SEQ ID NO: 100152 is W. 85. The antibody or antigen-binding fragment of any of embodiments 1, 54, 56, 58, and 60- 75, provided that the X; of SEQ ID NO: 100152is Y. 86. The antibody or antigen-binding fragment of any of embodiments 1, 54, 56, 58, and 60- 85, provided that the Xj of SEQ ID NO: 100155is Q. 87. The antibody or antigen-binding fragment of any of embodiments 1, 54, 56, 58, and 60- 85, provided that the X; of SEQ ID NO: 100155 is N. 88. The antibody or antigen-binding fragment of any of embodiments 1, 54, 56, 58, and 60- 87, provided that the Xz of SEQ ID NO: 100155 is D. 89. The antibody or antigen-binding fragment of any of embodiments 1, 54, 56, 58, and 60- 87, provided that the X; of SEQ ID NO: 100155is E. 90. The antibody or antigen-binding fragment of any of embodiments 1, 54, 56, 58, and 60- 87, provided that the X; of SEQ ID NO: 100155 is H. 91. The antibody or antigen-binding fragment of any of embodiments 1, 54, 56, 58, and 60- 87, provided that the X; of SEQ ID NO: 100155 is N. 92. The antibody or antigen-binding fragment of any of embodiments 1, 54, 56, 58, and 60- 87, provided that the X; of SEQ ID NO: 100155 is Q. 93. The antibody or antigen-binding fragment of any of embodiments 1, 54, 56, 58, and 60- 87, provided that the X; of SEQ ID NO: 100155 is S. 94. The antibody or antigen-binding fragment of any of embodiments 1, 54, 56, 58, and 60- 93, provided that the X; of SEQ ID NO: 100155 is A. 95. The antibody or antigen-binding fragment of any of embodiments 1, 54, 56, 58, and 60- 93, provided that the X; of SEQ ID NO: 100155 is G. 96. The antibody or antigen-binding fragment of any of embodiments 1, 54, 56, 58, and 60- 95, provided that the Xs of SEQ ID NO: 100155 is D. 97. The antibody or antigen-binding fragment of any of embodiments 1, 54, 56, 58, and 60- 95, provided that the Xs of SEQ ID NO: 100155 is F. 98. The antibody or antigen-binding fragment of any of embodiments 1, 54, 56, 58, and 60- 95, provided that the Xs of SEQ ID NO: 100155 is K. 99. The antibody or antigen-binding fragment of any of embodiments 1, 54, 56, 58, and 60- 95, provided that the Xs of SEQ ID NO: 100155 is N. 100. The antibody or antigen-binding fragment of any of embodiments 1, 54, 56, 58, and 60- 95, provided that the Xs of SEQ ID NO: 100155 is R. 101. The antibody or antigen-binding fragment of any of embodiments 1, 54, 56, 58, and 60- 95, provided that the Xs of SEQ ID NO: 100155 is S. 102. The antibody or antigen-binding fragment of any of embodiments 1, 54, 56, 58, and 60- 95, provided that the Xs of SEQ ID NO: 100155is T. 103. The antibody or antigen-binding fragment of any of embodiments 1-102, provided that the antibody or antigen-binding fragment specifically binds to human TL1A. 104. The antibody or antigen-binding fragment of embodiment 103, provided that the antibody or antigen-binding fragment specifically binds to human TL1A with a Kg of 1x10 M or less. 105. The antibody or antigen-binding fragment of embodiment 104, provided that the Kq is measured using a method selected from a standard ELISA assay and SPR. 106. The antibody or antigen-binding fragment of any of embodiments 1-105, provided that the antibody or antigen-binding fragment inhibits binding of DR3 to human TL1A. 107. The antibody or antigen-binding fragment of any of embodiments 1-106, provided that the antibody or antigen-binding fragment inhibits binding of DcR3 to human TL1A. 108. The antibody or antigen-binding fragment of any of embodiments 1-107, provided that the antibody or antigen-binding fragment is a humanized antibody, a CDR-grafted antibody, a chimeric antibody, a Fab, a ScFv, or a combination thereof. 109. The antibody or antigen-binding fragment of any of embodiments 1-108, comprising a human CHI domain. 110. The antibody or antigen-binding fragment of any of embodiments 1-109, comprising a human CH2 domain. 111. The antibody or antigen-binding fragment of embodiment 110, provided that that CH2 domain comprises at least one mutation selected from L234A, L235A, and G237A, as numbered using Kabat. 112. The antibody or antigen-binding fragment of any of embodiments 1-111, comprising a human CH3 domain. 113. A pharmaceutical composition comprising a therapeutically effective amount of the antibody or antigen-binding fragment of any of embodiments 1-112, and a pharmaceutically acceptable carrier. 114. A method of treating an inflammatory disease in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the antibody or antigen- binding fragment of any of embodiments 1-113. 115. The method of embodiment 114, provided that the inflammatory disease is inflammatory bowel disease. 116. The method of embodiment 115, provided that the inflammatory bowel disease comprises Crohn’s disease. 117. The method of embodiment 116, provided that the subject has been determined to be non- responsive to anti-TNF alpha therapy. 118. The method of embodiment 116 or embodiment 117, provided that the subject has been determined to comprise a disease phenotype comprising non-stricturing / non-penetrating, stricturing, stricturing and penetrating, or isolated internal penetrating. 119. An antibody or antigen-binding fragment that specifically binds to TL1A, comprising: a heavy chain variable region comprising four heavy chain framework regions (HFR1, HFR2, HFR3, and HFR4) comprising SEQ ID NOS: 100100-100103, and three heavy chain complementarity-determining regions (HCDR1, HCDR2, and HCDR3) comprising: (a) a HCDRI1 selected from: (i) a HCDR1 comprising SEQ ID NO: 1009, (ii) a HCDRI1 comprising SEQ ID NO: 100150, wherein Xj is selected from D and E, Xz is selected from I, P and V, X; is selected from G, Q, S, and V, Xu is selected from F and Y, and Xs is selected from I and M, (iii) a HCDR1 selected from SEQ ID NOS: 100200-100295, and (iv) a HCDR1 comprising an amino acid sequence that differs from a sequence selected from the group consisting of SEQ ID NOS: 1009, 100150 and 100200-100295 by up to five, four, three, or two amino acids, (b) a HCDR?2 selected from: (i) a HCDR2 comprising SEQ ID NO: 10012, and (ii) a HCDR2 comprising an amino acid sequence that differs from SEQ ID NO: 10012 by up to five, four, three, or two amino acids, and (c) a HCDR3 selected from (i) a HCDR3 comprising SEQ ID NO: 10015, (ii) a HCDR3 comprising SEQ ID NO: 100152, wherein Xj is selected from L and M, and Xz is selected from E, LK, L,M, Q, T, V, W, and Y, (iii) a HCDR3 selected from SEQ ID NOS: 100296-100314, and (iv) a HCDR3 comprising an amino acid sequence that differs from a sequence selected from the group consisting of SEQ ID NOS: 10015, 100152 and 100296-100314 by up to five, four, three, or two amino acids; and a light chain variable region comprising four light chain framework regions (LFR1, LFR2, LFR3, and LFR4) comprising SEQ ID NOS: 100104-100107, and three light chain complementarity-determining regions (LCDR1, LCDR2, and LCDR3) comprising: (a) a LCDRI selected from: (i) a LCDR1 comprising SEQ ID NO: 10018, and (ii) a LCDRI comprising an amino acid sequence that differs from SEQ ID NO: 10018 by up to five, four, three, or two amino acids, (b) a LCDR2 selected from: (i) a LCDR2 comprising SEQ ID NO: 10021, and (ii) a LCDR2 comprising an amino acid sequence that differs from SEQ ID NO: 10021 by up to five, four, three, or two amino acids, and (c) a LCDR3 selected from (i) a LCDR3 comprising SEQ ID NO: 10024, (ii) a LCDR3 comprising SEQ ID NO: 100155, wherein X is selected from Q and N, X; is selected from D, E, H, N, Q, and S, X; is selected from A and G, and Xs is selected from D, F, K, N, R, S, and T, (iii) a LCDR3 selected from SEQ ID NOS: 100315-100482, and (iv) a LCDR3 comprising an amino acid sequence that differs from a sequence selected from the group consisting of SEQ ID NOS: 10024, 100155, and 100315-100482 by up to five, four, three, or two amino acids. 120. The antibody or antigen-binding fragment of embodiment 119, provided that the HCDR1 comprises SEQ ID NO: 1009. 121. The antibody or antigen-binding fragment of embodiment 119, provided that the HCDR1 comprises SEQ ID NO: 100150. 122. The antibody or antigen-binding fragment of embodiment 121, provided that Xi is E. 123. The antibody or antigen-binding fragment of embodiment 121 or embodiment 122, provided that X is selected from P and V. 124. The antibody or antigen-binding fragment of any of embodiments 121-123, provided that X; is selected from G, S, and V. 125. The antibody or antigen-binding fragment of any of embodiments 121-124, provided that X;isF. 126. The antibody or antigen-binding fragment of any of embodiments 121-125, provided that Xsis I 127. The antibody or antigen-binding fragment of embodiment 119, provided that the HCDR1 comprises an amino acid sequence selected from SEQ ID NOS: 100200-100295. 128. The antibody or antigen-binding fragment of any of embodiments 119-127, provided that the HCDR2 comprises SEQ ID NO: 10012. 129. The antibody or antigen-binding fragment of any of embodiments 119-127, provided that the HCDR2 comprises an amino acid sequence that differs from SEQ ID NO: 10012 by up to five, four, three, or two amino acids. 130. The antibody or antigen-binding fragment of any of embodiments 119-129, provided that the HCDR3 comprises SEQ ID NO: 10015. 131. The antibody or antigen-binding fragment of any of embodiments 119-129, provided that the HCDR3 comprises SEQ ID NO: 100152. 132. The antibody or antigen-binding fragment of embodiment 131, provided that Xi is M. 133. The antibody or antigen-binding fragment of embodiment 131 or embodiment 132, provided that X; is selected from E, LK, L,M, Q, T, W, and Y. 134. The antibody or antigen-binding fragment of any of embodiments 119-129, provided that the HCDR3 comprises a sequence selected from SEQ ID NOS: 100296-100314. 135. The antibody or antigen-binding fragment of any of embodiments 119-134, provided that the LCDR1 comprises SEQ ID NO: 10018. 136. The antibody or antigen-binding fragment of any of embodiments 119-134, provided that the LCDR1 comprises an amino acid sequence that differs from SEQ ID NO: 10018 by up to five, four, three, or two amino acids. 137. The antibody or antigen-binding fragment of any of embodiments 119-136, provided that the LCDR2 comprises SEQ ID NO: 10021. 138. The antibody or antigen-binding fragment of any of embodiments 119-136, provided that the LCDR2 comprises an amino acid sequence that differs from SEQ ID NO: 10021 by up to five, four, three, or two amino acids. 139. The antibody or antigen-binding fragment of any of embodiments 119-138, provided that the LCDR3 comprises SEQ ID NO: 10024. 140. The antibody or antigen-binding fragment of any of embodiments 119-138, provided that the LCDR3 comprises SEQ ID NO: 100155. 141. The antibody or antigen-binding fragment of embodiment 140, provided that Xj is N. 142. The antibody or antigen-binding fragment of embodiment 140 or embodiment 141, provided that Xz is selected from D, E, H, N, and Q. 143. The antibody or antigen-binding fragment of any of embodiments 140-142, provided that X3is A. 144. The antibody or antigen-binding fragment of any of embodiments 140-143, provided that X4 is selected from D, F,K,R, S, and T. 145. The antibody or antigen-binding fragment of any of embodiments 119-138, provided that the LCDR3 comprises an amino acid sequence selected from SEQ ID NOS: 100315- 100482. 146. The antibody or antigen-binding fragment of embodiment 119, provided that the HCDR1 comprises SEQ ID NO: 1009, the HCDR2 comprises SEQ ID NO: 10012, the HCDR3 comprises SEQ ID NO: 10015, the LCDR1 comprises SEQ ID NO: 10018, the LCDR2 comprises SEQ ID NO: 10021, and the LCDR3 comprises SEQ ID NO: 10024. 147. The antibody or antigen-binding fragment of embodiment 119, provided that the HCDR 1 comprises SEQ ID NO: 100150, the HCDR2 comprises SEQ ID NO: 10012, the HCDR3 comprises SEQ ID NO: 100152, the LCDR1 comprises SEQ ID NO: 10018, the LCDR2 comprises SEQ ID NO: 10021, and the LCDR3 comprises SEQ ID NO: 100155. 148. The antibody or antigen-binding fragment of embodiment 119 or embodiment 147, provided that the X; of SEQ ID NO: 100150 is D. 149. The antibody or antigen-binding fragment of embodiment 119 or embodiment 147 provided that the X; of SEQ ID NO: 100150 is E. 150. The antibody or antigen-binding fragment of any of embodiments 119, 147-149, provided that the X, of SEQ ID NO: 100150is I, 151. The antibody or antigen-binding fragment of any of embodiments 119, 147-149, provided that the X; of SEQ ID NO: 100150 is P. 152. The antibody or antigen-binding fragment of any of embodiments 119, 147-149, provided that the X; of SEQ ID NO: 100150 is V. 153. The antibody or antigen-binding fragment of any of embodiments 119, 147-152, provided that the X; of SEQ ID NO: 100150 is G. 154. The antibody or antigen-binding fragment of any of embodiments 119, 147-152, provided that the X; of SEQ ID NO: 100150 is Q. 155. The antibody or antigen-binding fragment of any of embodiments 119, 147-152, provided that the X3 of SEQ ID NO: 100150 is S. 156. The antibody or antigen-binding fragment of any of embodiments 119, 147-152, provided that the X3 of SEQ ID NO: 100150 is V. 157. The antibody or antigen-binding fragment of any of embodiments 119, 147-156, provided that the X4 of SEQ ID NO: 100150 is F. 158. The antibody or antigen-binding fragment of any of embodiments 119, 147-156, provided that the X4 of SEQ ID NO: 100150is Y. 159. The antibody or antigen-binding fragment of any of embodiments 119, 147-158, provided that the Xs of SEQ ID NO: 100150 is I. 160. The antibody or antigen-binding fragment of any of embodiments 119, 147-158, provided that the Xs of SEQ ID NO: 100150 is M. 161. The antibody or antigen-binding fragment of any of embodiments 119, 147-160, provided that the Xi of SEQ ID NQ: 100152 is L. 162. The antibody or antigen-binding fragment of any of embodiments 119, 147-160, provided that the Xi of SEQ ID NO: 100152 is M. 163. The antibody or antigen-binding fragment of any of embodiments 119, 147-162, provided that the X; of SEQ ID NO: 100152 is E. 164. The antibody or antigen-binding fragment of any of embodiments 119, 147-162, provided that the X; of SEQ ID NO: 100152 is I. 165. The antibody or antigen-binding fragment of any of embodiments 119, 147-162, provided that the X; of SEQ ID NO: 100152 is K. 166. The antibody or antigen-binding fragment of any of embodiments 119, 147-162, provided that the X; of SEQ ID NQ: 100152 is L. 167. The antibody or antigen-binding fragment of any of embodiments 119, 147-162, provided that the X, of SEQ ID NO: 100152 is M., 168. The antibody or antigen-binding fragment of any of embodiments 119, 147-162, provided that the X; of SEQ ID NO: 100152 is Q. 169. The antibody or antigen-binding fragment of any of embodiments 119, 147-162, provided that the X; of SEQ ID NO: 100152 is T. 170. The antibody or antigen-binding fragment of any of embodiments 119, 147-162, provided that the X; of SEQ ID NQ: 100152 is V. 171. The antibody or antigen-binding fragment of any of embodiments 119, 147-162, provided that the X, of SEQ ID NO: 100152 is W. 172. The antibody or antigen-binding fragment of any of embodiments 119, 147-162, provided that the X; of SEQ ID NO: 100152 is Y. 173. The antibody or antigen-binding fragment of any of embodiments 119, 147-172, provided that the Xi of SEQ ID NO: 100155 is Q. 174. The antibody or antigen-binding fragment of any of embodiments 119, 147-172, provided that the Xi of SEQ ID NO: 100155 is N. 175. The antibody or antigen-binding fragment of any of embodiments 119, 147-174, provided that the X; of SEQ ID NO: 100155 is D. 176. The antibody or antigen-binding fragment of any of embodiments 119, 147-174, provided that the X; of SEQ ID NO: 100155 is E. 177. The antibody or antigen-binding fragment of any of embodiments 119, 147-174, provided that the X; of SEQ ID NO: 100155 is H. 178. The antibody or antigen-binding fragment of any of embodiments 119, 147-174, provided that the X, of SEQ ID NO: 100155 is N. 179. The antibody or antigen-binding fragment of any of embodiments 119, 147-174, provided that the X, of SEQ ID NO: 100155 is Q. 180. The antibody or antigen-binding fragment of any of embodiments 119, 147-174, provided that the X; of SEQ ID NO: 100155 is S. 181. The antibody or antigen-binding fragment of any of embodiments 119, 147-180, provided that the X3 of SEQ ID NO: 100155 is A. 182. The antibody or antigen-binding fragment of any of embodiments 119, 147-180, provided that the X;3 of SEQ ID NO: 100155 is G. 183. The antibody or antigen-binding fragment of any of embodiments 119, 147-182, provided that the Xs of SEQ ID NO: 100155 is D. 184. The antibody or antigen-binding fragment of any of embodiments 119, 147-182, provided that the Xs of SEQ ID NO: 100155 is F. 185. The antibody or antigen-binding fragment of any of embodiments 119, 147-182, provided that the X34 of SEQ ID NO: 100155 is K. 186. The antibody or antigen-binding fragment of any of embodiments 119, 147-182, provided that the X3 of SEQ ID NO: 100155 is N. 187. The antibody or antigen-binding fragment of any of embodiments 119, 147-182, provided that the Xs of SEQ ID NO: 100155 is R. 188. The antibody or antigen-binding fragment of any of embodiments 119, 147-182, provided that the Xs of SEQ ID NO: 100155 is S. 189. The antibody or antigen-binding fragment of any of embodiments 119, 147-182, provided that the X4 of SEQ ID NO: 100155is T. 190. The antibody or antigen-binding fragment of any of embodiments 119-189, provided that the antibody or antigen-binding fragment specifically binds to human TL1A. 191. The antibody or antigen-binding fragment of embodiment 190, provided that the antibody or antigen-binding fragment specifically binds to human TLI1A with a Kg of 1x10° M or less. 192. The antibody or antigen-binding fragment of embodiment 191, provided that the Kq is measured using a method selected from a standard ELISA assay and SPR. 193. The antibody or antigen-binding fragment of any of embodiments 119-192, provided that the antibody or antigen-binding fragment inhibits binding of DR3 to human TL1A. 194. The antibody or antigen-binding fragment of any of embodiments 119-193, provided that the antibody or antigen-binding fragment inhibits binding of DcR3 to human TL1A. 195. The antibody or antigen-binding fragment of any of embodiments 119-194, provided that the antibody or antigen-binding fragment is a humanized antibody, a CDR-grafted antibody, a chimeric antibody, a Fab, a ScFv, or a combination thereof. 196. The antibody or antigen-binding fragment of any of embodiments 119-195, comprising a human CH1 domain. 197. The antibody or antigen-binding fragment of any of embodiments 119-196, comprising a human CH?2 domain. 198. The antibody or antigen-binding fragment of embodiment 197, provided that that CH2 domain comprises at least one mutation selected from L234A, L235A, and G237A, as numbered using Kabat, 199. The antibody or antigen-binding fragment of any of embodiments 119-198, comprising a human CH3 domain. 200. A pharmaceutical composition comprising a therapeutically effective amount of the antibody or antigen-binding fragment of any of embodiments 119-199, and a pharmaceutically acceptable carrier. 201. A method of treating an inflammatory disease in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the antibody or antigen- binding fragment of any of embodiments 119-199. 202. The method of embodiment 201, provided that the inflammatory disease is inflammatory bowel disease. 203. The method of embodiment 202, provided that the inflammatory bowel disease comprises Crohn’s disease. 204. The method of embodiment 203, provided that the subject has been determined to be non- responsive to anti-TNF alpha therapy. 205. The method of embodiment 203 or embodiment 204, provided that the subject has been determined to comprise a disease phenotype comprising non-stricturing / non-penetrating, stricturing, stricturing and penetrating, or isolated internal penetrating. 206. An antibody or antigen-binding fragment that specifically binds to TL1A, comprising: a heavy chain variable region comprising four heavy chain framework regions (HFR1, HFR2, HFR3, and HFR4) comprising SEQ ID NOS: 100108, 100101, 100109, and 100103, respectively, and three heavy chain complementarity-determining regions (HCDR1, HCDR2, and HCDR3) comprising; (a) a HCDRI1 selected from: (i) a HCDR1 comprising SEQ ID NO: 1009, (ii) a HCDRI1 comprising SEQ ID NO: 100150, wherein Xj is selected from D and E, Xz is selected from I, P and V, X; is selected from G, Q, S, and V, Xu is selected from F and Y, and Xs is selected from I and M, (iii) a HCDR1 selected from SEQ ID NOS: 100200-100295, and (iv) a HCDR1 comprising an amino acid sequence that differs from a sequence selected from the group consisting of SEQ ID NOS: 1009, 100150 and 100200-100295 by up to five, four, three, or two amino acids, (b) a HCDR2 selected from: (i) a HCDR2 comprising SEQ ID NO: 10012, and (ii) a HCDR2 comprising an amino acid sequence that differs from SEQ ID NO: 10012 by up to five, four, three, or two amino acids, and (c) a HCDR3 selected from (i) a HCDR3 comprising SEQ ID NO: 10015, (ii) a HCDR3 comprising SEQ ID NO: 100152, wherein X; is selected from L and M, and X; is selected from E, LK, L,M, Q, T, V, W, and Y, (iii) a HCDR3 selected from SEQ ID NOS: 100296-100314, and (iv) a HCDR3 comprising an amino acid sequence that differs from a sequence selected from the group consisting of SEQ ID NOS: 10015, 100152 and 100296-100314 by up to five, four, three, or two amino acids; and a light chain variable region comprising four light chain framework regions (LFR1, LFR2, LFR3, and LFR4) comprising SEQ ID NOS: 100104, 100105, 100110, and 100107, respectively, and three light chain complementarity-determining regions (LCDR1, LCDR2, and LCDR3) comprising; (a) a LCDRI selected from: (i) a LCDR1 comprising SEQ ID NO: 10018, and (ii) a LCDRI comprising an amino acid sequence that differs from SEQ ID NO: 10018 by up to five, four, three, or two amino acids, (b) a LCDR2 selected from: (i) a LCDR2 comprising SEQ ID NO: 10021, and (ii) a LCDR2 comprising an amino acid sequence that differs from SEQ ID NO: 10021 by up to five, four, three, or two amino acids, and (©) a LCDR3 selected from (i) a LCDR3 comprising SEQ ID NO: 10024, (ii) a LCDR3 comprising SEQ ID NO: 100155, wherein X is selected from Q and N, X; is selected from D, E, H, N, Q, and S, X; is selected from A and G, and Xs is selected from D, F, K, N, R, S, and T, (iii) a LCDR3 selected from SEQ ID NOS: 100315-100482, and (iv) a LCDR3 comprising an amino acid sequence that differs from a sequence selected from the group consisting of SEQ ID NOS: 10024, 100155, and 100315-100482 by up to five, four, three, or two amino acids. 207. The antibody or antigen-binding fragment of embodiment 206, provided that the HCDR1 comprises SEQ ID NO: 1009. 208. The antibody or antigen-binding fragment of embodiment 206, provided that the HCDR1 comprises SEQ ID NO: 100150. 209. The antibody or antigen-binding fragment of embodiment 208, provided that X; is E. 210. The antibody or antigen-binding fragment of embodiment 208 or embodiment 209, provided that X is selected from P and V. 211. The antibody or antigen-binding fragment of any of embodiments 208-210, provided that X3 is selected from G, S, and V. 212. The antibody or antigen-binding fragment of any of embodiments 208-211, provided that X:isF. 213. The antibody or antigen-binding fragment of any of embodiments 208-212, provided that Xsis I. 214. The antibody or antigen-binding fragment of embodiment 206, provided that the HCDR1 comprises an amino acid sequence selected from SEQ ID NOS: 100200-100295. 215. The antibody or antigen-binding fragment of any of embodiments 206-214, provided that the HCDR2 comprises SEQ ID NO: 10012. 216. The antibody or antigen-binding fragment of any of embodiments 206-214, provided that the HCDR2 comprises an amino acid sequence that differs from SEQ ID NO: 10012 by up to five, four, three, or two amino acids. 217. The antibody or antigen-binding fragment of any of embodiments 206-216, provided that the HCDR3 comprises SEQ ID NO: 10015. 218. The antibody or antigen-binding fragment of any of embodiments 206-216, provided that the HCDR3 comprises SEQ ID NO: 100152. 219. The antibody or antigen-binding fragment of embodiment 218, provided that Xi is M. 220. The antibody or antigen-binding fragment of embodiment 218 or embodiment 219, provided that X; is selected from E, LK, L,M, Q, T, W, and Y. 221. The antibody or antigen-binding fragment of any of embodiments 206-220, provided that the HCDR3 comprises a sequence selected from SEQ ID NOS: 100296-100314. 222. The antibody or antigen-binding fragment of any of embodiments 206-221, provided that the LCDR1 comprises SEQ ID NO: 10018. 223. The antibody or antigen-binding fragment of any of embodiments 206-221, provided that the LCDR1 comprises an amino acid sequence that differs from SEQ ID NO: 10018 by up to five, four, three, or two amino acids. 224. The antibody or antigen-binding fragment of any of embodiments 206-223, provided that the LCDR2 comprises SEQ ID NO: 10021. 225. The antibody or antigen-binding fragment of any of embodiments 206-223, provided that the LCDR2 comprises an amino acid sequence that differs from SEQ ID NO: 10021 by up to five, four, three, or two amino acids. 226. The antibody or antigen-binding fragment of any of embodiments 206-225, provided that the LCDR3 comprises SEQ ID NO: 10024. 227. The antibody or antigen-binding fragment of any of embodiments 206-225, provided that the LCDR3 comprises SEQ ID NO: 100155. 228. The antibody or antigen-binding fragment of embodiment 227, provided that X is N. 229. The antibody or antigen-binding fragment of embodiment 227 or embodiment 228, provided that X; is selected from D, E, H, N, and Q. 230. The antibody or antigen-binding fragment of any of embodiments 227-229, provided that X3is A. 231. The antibody or antigen-binding fragment of any of embodiments 227-230, provided that X4 is selected from D,F, KR, S, and T. 232. The antibody or antigen-binding fragment of any of embodiments 227-231, provided that the LCDR3 comprises an amino acid sequence selected from SEQ ID NOS: 100315- 100482. 233. The antibody or antigen-binding fragment of embodiment 206, provided that the HCDR1 comprises SEQ ID NO: 1009, the HCDR2 comprises SEQ ID NO: 10012, the HCDR3 comprises SEQ ID NO: 10015, the LCDR1 comprises SEQ ID NO: 10018, the LCDR2 comprises SEQ ID NO: 10021, and the LCDR3 comprises SEQ ID NO: 10024. 234. The antibody or antigen-binding fragment of embodiment 206, provided that the HCDR 1 comprises SEQ ID NO: 100150, the HCDR2 comprises SEQ ID NO: 10012, the HCDR3 comprises SEQ ID NO: 100152, the LCDR1 comprises SEQ ID NO: 10018, the LCDR2 comprises SEQ ID NO: 10021, and the LCDR3 comprises SEQ ID NO: 100155. 235. The antibody or antigen-binding fragment of embodiment 206 or embodiment 234, provided that the X; of SEQ ID NO: 100150 is D. 236. The antibody or antigen-binding fragment of embodiment 206 or embodiment 234 provided that the X; of SEQ ID NO: 100150 is E. 237. The antibody or antigen-binding fragment of any of embodiments 206, 234-236, provided that the X, of SEQ ID NO: 100150is I, 238. The antibody or antigen-binding fragment of any of embodiments 206, 234-236, provided that the X; of SEQ ID NO: 100150 is P. 239. The antibody or antigen-binding fragment of any of embodiments 206, 234-236, provided that the X; of SEQ ID NO: 100150 is V. 240. The antibody or antigen-binding fragment of any of embodiments 206, 234-239, provided that the X;3 of SEQ ID NO: 100150 is G. 241. The antibody or antigen-binding fragment of any of embodiments 206, 234-239, provided that the X; of SEQ ID NO: 100150 is Q. 242. The antibody or antigen-binding fragment of any of embodiments 206, 234-239, provided that the Xs of SEQ ID NO: 1001501is S. 243. The antibody or antigen-binding fragment of any of embodiments 206, 234-239, provided that the X3 of SEQ ID NO: 100150 is V. 244. The antibody or antigen-binding fragment of any of embodiments 206, 234-243, provided that the Xs of SEQ ID NO: 100150 is F. 245. The antibody or antigen-binding fragment of any of embodiments 206, 234-243, provided that the Xs of SEQ ID NQ: 100150is Y. 246. The antibody or antigen-binding fragment of any of embodiments 206, 234-245, provided that the Xs of SEQ ID NO: 100150is I, 247. The antibody or antigen-binding fragment of any of embodiments 206, 234-245, provided that the Xs of SEQ ID NO: 100150 is M. 248. The antibody or antigen-binding fragment of any of embodiments 206, 234-247, provided that the Xi of SEQ ID NO: 100152 is L. 249. The antibody or antigen-binding fragment of any of embodiments 206, 234-247, provided that the Xi of SEQ ID NO: 100152 is M. 250. The antibody or antigen-binding fragment of any of embodiments 206, 234-249, provided that the X; of SEQ ID NO: 100152 is E. 251. The antibody or antigen-binding fragment of any of embodiments 206, 234-249, provided that the X; of SEQ ID NO: 100152 is I. 252. The antibody or antigen-binding fragment of any of embodiments 206, 234-249, provided that the X; of SEQ ID NO: 100152 is K. 253. The antibody or antigen-binding fragment of any of embodiments 206, 234-249, provided that the X; of SEQ ID NQ: 100152 is L. 254. The antibody or antigen-binding fragment of any of embodiments 206, 234-249, provided that the X, of SEQ ID NO: 100152 is M., 255. The antibody or antigen-binding fragment of any of embodiments 206, 234-249, provided that the X; of SEQ ID NO: 100152 is Q. 256. The antibody or antigen-binding fragment of any of embodiments 206, 234-249, provided that the X; of SEQ ID NO: 100152 is T. 257. The antibody or antigen-binding fragment of any of embodiments 206, 234-249, provided that the X; of SEQ ID NO: 100152 is V. 258. The antibody or antigen-binding fragment of any of embodiments 206, 234-249, provided that the X, of SEQ ID NO: 100152 is W. 259. The antibody or antigen-binding fragment of any of embodiments 206, 234-249, provided that the X; of SEQ ID NQ: 100152 is Y. 260. The antibody or antigen-binding fragment of any of embodiments 206, 234-259, provided that the X; of SEQ ID NO: 100155 is Q. 261. The antibody or antigen-binding fragment of any of embodiments 206, 234-259, provided that the Xi of SEQ ID NO: 100155 is N. 262. The antibody or antigen-binding fragment of any of embodiments 206, 234-261, provided that the X, of SEQ ID NO: 100155 is D. 263. The antibody or antigen-binding fragment of any of embodiments 206, 234-261, provided that the X; of SEQ ID NO: 100155 is E. 264. The antibody or antigen-binding fragment of any of embodiments 206, 234-261, provided that the X; of SEQ ID NO: 100155 is H. 265. The antibody or antigen-binding fragment of any of embodiments 206, 234-261, provided that the X; of SEQ ID NO: 100155 is N. 266. The antibody or antigen-binding fragment of any of embodiments 206, 234-261, provided that the X; of SEQ ID NO: 100155 is Q. 267. The antibody or antigen-binding fragment of any of embodiments 206, 234-261, provided that the Xz of SEQ ID NO: 100155 is S. 268. The antibody or antigen-binding fragment of any of embodiments 206, 234-267, provided that the X3 of SEQ ID NO: 100155 is A. 269. The antibody or antigen-binding fragment of any of embodiments 206, 234-267, provided that the X3 of SEQ ID NO: 100155 is G. 270. The antibody or antigen-binding fragment of any of embodiments 206, 234-269, provided that the Xs of SEQ ID NO: 100155 is D. 271. The antibody or antigen-binding fragment of any of embodiments 206, 234-269, provided that the Xs of SEQ ID NO: 100155 is F. 272. The antibody or antigen-binding fragment of any of embodiments 206, 234-269, provided that the X34 of SEQ ID NO: 100155 is K. 273. The antibody or antigen-binding fragment of any of embodiments 206, 234-269, provided that the X4 of SEQ ID NO: 100155 is N. 274. The antibody or antigen-binding fragment of any of embodiments 206, 234-269, provided that the X4 of SEQ ID NO: 100155 is R. 275. The antibody or antigen-binding fragment of any of embodiments 206, 234-269, provided that the Xs of SEQ ID NO: 100155 is S. 276. The antibody or antigen-binding fragment of any of embodiments 206, 234-269, provided that the Xs of SEQ ID NQ: 100155is T. 277. The antibody or antigen-binding fragment of any of embodiments 206-276, provided that the antibody or antigen-binding fragment specifically binds to human TL1A. 278. The antibody or antigen-binding fragment of embodiment 277, provided that the antibody or antigen-binding fragment specifically binds to human TL1A with a Kg of 1x10 M or less. 279. The antibody or antigen-binding fragment of embodiment 278, provided that the Kq is measured using a method selected from a standard ELISA assay and SPR. 280. The antibody or antigen-binding fragment of any of embodiments 206-279, provided that the antibody or antigen-binding fragment inhibits binding of DR3 to human TL1A. 281. The antibody or antigen-binding fragment of any of embodiments 206-280, provided that the antibody or antigen-binding fragment inhibits binding of DcR3 to human TL1A. 282. The antibody or antigen-binding fragment of any of embodiments 206-281, provided that the antibody or antigen-binding fragment is a humanized antibody, a CDR-grafted antibody, a chimeric antibody, a Fab, a ScFv, or a combination thereof. 283. The antibody or antigen-binding fragment of any of embodiments 206-282, comprising a human CHI domain. 284. The antibody or antigen-binding fragment of any of embodiments 206-283, comprising a human CH?2 domain. 285. The antibody or antigen-binding fragment of embodiment 284, provided that that CH2 domain comprises at least one mutation selected from L234A, L235A, and G237A, as numbered using Kabat, 286. The antibody or antigen-binding fragment of any of embodiments 206-285, comprising a human CH3 domain. 287. A pharmaceutical composition comprising a therapeutically effective amount of the antibody or antigen-binding fragment of any of embodiments 206-286, and a pharmaceutically acceptable carrier. 288. A method of treating an inflammatory disease in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the antibody or antigen- binding fragment of any of embodiments 206-287. 289. The method of embodiment 288, provided that the inflammatory disease is inflammatory bowel disease. 290. The method of embodiment 289, provided that the inflammatory bowel disease comprises Crohn’s disease. 291. The method of embodiment 290, provided that the subject has been determined to be non- responsive to anti-TNF alpha therapy. 292. The method of embodiment 290 or embodiment 291, provided that the subject has been determined to comprise a disease phenotype comprising non-stricturing / non-penetrating, stricturing, stricturing and penetrating, or isolated internal penetrating. 293. An antibody or antigen-binding fragment that specifically binds to TL1A, comprising: a heavy chain variable region comprising four heavy chain framework regions (HFR1, HFR2, HFR3, and HFR4) comprising SEQ ID NOS: 100108, 100101, 100109, and 100103, respectively, and three heavy chain complementarity-determining regions (HCDR1, HCDR2, and HCDR3) comprising: (a) a HCDR1 selected from: (i) a HCDR1 comprising SEQ ID NO: 1009, (ii) a HCDRI1 comprising SEQ ID NO: 100150, wherein Xj is selected from D and E, Xz is selected from I, P and V, X; is selected from G, Q, S, and V, Xu is selected from F and Y, and Xs is selected from I and M, (iii) a HCDR1 selected from SEQ ID NOS: 100200-100295, and (iv) a HCDR1 comprising an amino acid sequence that differs from a sequence selected from the group consisting of SEQ ID NOS: 1009, 100150 and 100200-100295 by up to five, four, three, or two amino acids, (b) a HCDR2 selected from: (i) a HCDR2 comprising SEQ ID NO: 10012, and (ii) a HCDR2 comprising an amino acid sequence that differs from SEQ ID NO: 10012 by up to five, four, three, or two amino acids, and (c) a HCDR3 selected from (i) a HCDR3 comprising SEQ ID NO: 10015, (ii) a HCDR3 comprising SEQ ID NO: 100152, wherein Xj is selected from L and M, and Xz is selected from E, LK, L,M, Q, T, V, W, and Y, (iii) a HCDR3 selected from SEQ ID NOS: 100296-100314, and (iv) a HCDR3 comprising an amino acid sequence that differs from a sequence selected from the group consisting of SEQ ID NOS: 10015, 100152 and 100296-100314 by up to five, four, three, or two amino acids; and a light chain variable region comprising four light chain framework regions (LFR1, LFR2, LFR3, and LFR4) comprising SEQ ID NOS: 100104-100107, and three light chain complementarity-determining regions (LCDR1, LCDR2, and LCDR3) comprising: (a) a LCDRI1 selected from: (i) a LCDR 1 comprising SEQ ID NO: 10018, and (ii) a LCDRI comprising an amino acid sequence that differs from SEQ ID NO: 10018 by up to five, four, three, or two amino acids, (b) aLCDR2 selected from: (i) a LCDR2 comprising SEQ ID NO: 10021, and (ii) a LCDR2 comprising an amino acid sequence that differs from SEQ ID NO: 10021 by up to five, four, three, or two amino acids, and (c) a LCDR3 selected from (i) a LCDR3 comprising SEQ ID NO: 10024, (ii) a LCDR3 comprising SEQ ID NO: 100155, wherein Xi is selected from Q and N, X; is selected from D, E, H, N, Q, and S, X; is selected from A and G, and Xs is selected from D, F, K, N, R, S, and T, (iii) a LCDR3 selected from SEQ ID NOS: 100315-100482, and (iv) a LCDR3 comprising an amino acid sequence that differs from a sequence selected from the group consisting of SEQ ID NOS: 10024, 100155, and 100315-100482 by up to five, four, three, or two amino acids. 294. The antibody or antigen-binding fragment of embodiment 293, provided that the HCDR1 comprises SEQ ID NO: 1009. 295. The antibody or antigen-binding fragment of embodiment 293, provided that the HCDR1 comprises SEQ ID NO: 100150. 296. The antibody or antigen-binding fragment of embodiment 295, provided that X; is E. 297. The antibody or antigen-binding fragment of embodiment 295 or embodiment 296, provided that X; is selected from P and V. 298. The antibody or antigen-binding fragment of any of embodiments 295-297, provided that X3 is selected from G, S, and V. 299. The antibody or antigen-binding fragment of any of embodiments 295-298, provided that XsisF. 300. The antibody or antigen-binding fragment of any of embodiments 295-299, provided that Xsis I 301. The antibody or antigen-binding fragment of embodiment 293, provided that the HCDR1 comprises an amino acid sequence selected from SEQ ID NOS: 100200-100295. 302. The antibody or antigen-binding fragment of any of embodiments 293-301, provided that the HCDR2 comprises SEQ ID NO: 10012. 303. The antibody or antigen-binding fragment of any of embodiments 293-301 provided that the HCDR2 comprises an amino acid sequence that differs from SEQ ID NO: 10012 by up to five, four, three, or two amino acids. 304. The antibody or antigen-binding fragment of any of embodiments 293-303, provided that the HCDR3 comprises SEQ ID NO: 10015. 305. The antibody or antigen-binding fragment of any of embodiments 293-303, provided that the HCDR3 comprises SEQ ID NO: 100152. 306. The antibody or antigen-binding fragment of embodiment 305, provided that X) is M. 307. The antibody or antigen-binding fragment of embodiment 305 or embodiment 306, provided that Xz is selected from E, IL K, LM, Q, T, W, and Y. 308. The antibody or antigen-binding fragment of any of embodiments 293-303, provided that the HCDR3 comprises a sequence selected from SEQ ID NOS: 100296-100314. 309. The antibody or antigen-binding fragment of any of embodiments 293-308, provided that the LCDR comprises SEQ ID NO: 10018. 310. The antibody or antigen-binding fragment of any of embodiments 293-308, provided that the LCDR1 comprises an amino acid sequence that differs from SEQ ID NO: 10018 by up to five, four, three, or two amino acids. 311. The antibody or antigen-binding fragment of any of embodiments 293-310, provided that the LCDR2 comprises SEQ ID NO: 10021. 312. The antibody or antigen-binding fragment of any of embodiments 293-310, provided that the LCDR2 comprises an amino acid sequence that differs from SEQ ID NO: 10021 by up to five, four, three, or two amino acids. 313. The antibody or antigen-binding fragment of any of embodiments 293-312, provided that the LCDR3 comprises SEQ ID NO: 10024. 314. The antibody or antigen-binding fragment of any of embodiments 293-312, provided that the LCDR3 comprises SEQ ID NO: 100155. 315. The antibody or antigen-binding fragment of embodiment 314, provided that Xi is N. 316. The antibody or antigen-binding fragment of embodiment 314 or embodiment 315, provided that X; is selected from D, E, H, N, and Q. 317. The antibody or antigen-binding fragment of any of embodiments 314-316, provided that X:is A. 318. The antibody or antigen-binding fragment of any of embodiments 314-317, provided that Xyis selected from D,F, KR, S, and T. 319. The antibody or antigen-binding fragment of any of embodiments 314-312, provided that the LCDR3 comprises an amino acid sequence selected from SEQ ID NOS: 100315- 100482. 320. The antibody or antigen-binding fragment of embodiment 293, provided that the HCDR 1 comprises SEQ ID NO: 1009, the HCDR2 comprises SEQ ID NO: 10012, the HCDR3 comprises SEQ ID NO: 10015, the LCDR1 comprises SEQ ID NO: 10018, the LCDR2 comprises SEQ ID NO: 10021, and the LCDR3 comprises SEQ ID NO: 10024. 321. The antibody or antigen-binding fragment of embodiment 293, provided that the HCDR1 comprises SEQ ID NO: 100150, the HCDR2 comprises SEQ ID NO: 10012, the HCDR3 comprises SEQ ID NO: 100152, the LCDR1 comprises SEQ ID NO: 10018, the LCDR2 comprises SEQ ID NO: 10021, and the LCDR3 comprises SEQ ID NO: 100155. 322. The antibody or antigen-binding fragment of embodiment 293 or embodiment 321, provided that the X; of SEQ ID NO: 100150 is D. 323. The antibody or antigen-binding fragment of embodiment 293 or embodiment 321 provided that the X; of SEQ ID NO: 100150 is E. 324. The antibody or antigen-binding fragment of any of embodiments 293, 321-323, provided that the X; of SEQ ID NO: 100150 is I. 325. The antibody or antigen-binding fragment of any of embodiments 293, 321-323, provided that the Xz of SEQ ID NO: 100150 is P. 326. The antibody or antigen-binding fragment of any of embodiments 293, 321-323, provided that the X; of SEQ ID NO: 100150 is V. 327. The antibody or antigen-binding fragment of any of embodiments 293, 321-326, provided that the X3 of SEQ ID NO: 100150 is G. 328. The antibody or antigen-binding fragment of any of embodiments 293, 321-326, provided that the X; of SEQ ID NO: 100150 is Q. 329. The antibody or antigen-binding fragment of any of embodiments 293, 321-326, provided that the Xs of SEQ ID NO: 1001501is S. 330. The antibody or antigen-binding fragment of any of embodiments 293, 321-326, provided that the X3 of SEQ ID NO: 100150 is V. 331. The antibody or antigen-binding fragment of any of embodiments 293, 321-330, provided that the Xs of SEQ ID NO: 100150 is F. 332. The antibody or antigen-binding fragment of any of embodiments 293, 321-330, provided that the Xs of SEQ ID NQ: 100150is Y. 333. The antibody or antigen-binding fragment of any of embodiments 293, 321-332, provided that the Xs of SEQ ID NO: 1001501is I, 334. The antibody or antigen-binding fragment of any of embodiments 293, 321-332, provided that the Xs of SEQ ID NO: 100150 is M., 335. The antibody or antigen-binding fragment of any of embodiments 293, 321-334, provided that the Xi of SEQ ID NO: 100152 is L. 336. The antibody or antigen-binding fragment of any of embodiments 293, 321-334, provided that the Xi of SEQ ID NO: 100152 is M. 337. The antibody or antigen-binding fragment of any of embodiments 293, 321-336, provided that the X, of SEQ ID NO: 100152 is E. 338. The antibody or antigen-binding fragment of any of embodiments 293, 321-336, provided that the X, of SEQ ID NO: 100152 is I, 339. The antibody or antigen-binding fragment of any of embodiments 293, 321-336, provided that the X; of SEQ ID NO: 100152 is K. 340. The antibody or antigen-binding fragment of any of embodiments 293, 321-336, provided that the X; of SEQ ID NO: 100152 is L. 341. The antibody or antigen-binding fragment of any of embodiments 293, 321-336, provided that the X; of SEQ ID NO: 100152 is M. 342. The antibody or antigen-binding fragment of any of embodiments 293, 321-336, provided that the X; of SEQ ID NO: 100152 is Q. 343. The antibody or antigen-binding fragment of any of embodiments 293, 321-336, provided that the X; of SEQ ID NO: 100152 is T. 344. The antibody or antigen-binding fragment of any of embodiments 293, 321-336, provided that the X; of SEQ ID NO: 100152 is V. 345. The antibody or antigen-binding fragment of any of embodiments 293, 321-336, provided that the X, of SEQ ID NO: 100152 is W. 346. The antibody or antigen-binding fragment of any of embodiments 293, 321-336, provided that the X; of SEQ ID NQ: 100152 is Y. 347. The antibody or antigen-binding fragment of any of embodiments 293, 321-346, provided that the X; of SEQ ID NO: 100155 is Q. 348. The antibody or antigen-binding fragment of any of embodiments 293, 321-346, provided that the Xi of SEQ ID NO: 100155 is N. 349. The antibody or antigen-binding fragment of any of embodiments 293, 321-348, provided that the X; of SEQ ID NO: 100155 is D. 350. The antibody or antigen-binding fragment of any of embodiments 293, 321-348, provided that the X; of SEQ ID NO: 100155 is E. 351. The antibody or antigen-binding fragment of any of embodiments 293, 321-348, provided that the X, of SEQ ID NO: 100155 is H. 352. The antibody or antigen-binding fragment of any of embodiments 293, 321-348, provided that the X; of SEQ ID NO: 100155 is N. 353. The antibody or antigen-binding fragment of any of embodiments 293, 321-348, provided that the X; of SEQ ID NO: 100155 is Q. 354. The antibody or antigen-binding fragment of any of embodiments 293, 321-348, provided that the X, of SEQ ID NO: 100155 is S. 355. The antibody or antigen-binding fragment of any of embodiments 293, 321-354, provided that the X; of SEQ ID NO: 100155 is A. 356. The antibody or antigen-binding fragment of any of embodiments 293, 321-354, provided that the X3 of SEQ ID NO: 100155 is G. 357. The antibody or antigen-binding fragment of any of embodiments 293, 321-356, provided that the X3 of SEQ ID NO: 100155 is D. 358. The antibody or antigen-binding fragment of any of embodiments 293, 321-356, provided that the X4 of SEQ ID NO: 100155 is F. 359. The antibody or antigen-binding fragment of any of embodiments 293, 321-356, provided that the X4 of SEQ ID NO: 100155 is K. 360. The antibody or antigen-binding fragment of any of embodiments 293, 321-356, provided that the X4 of SEQ ID NO: 100155 is N. 361. The antibody or antigen-binding fragment of any of embodiments 293, 321-356, provided that the Xs of SEQ ID NO: 100155 is R. 362. The antibody or antigen-binding fragment of any of embodiments 293, 321-356, provided that the Xs of SEQ ID NO: 100155 is S. 363. The antibody or antigen-binding fragment of any of embodiments 293, 321-356, provided that the Xs of SEQ ID NQ: 100155is T. 364. The antibody or antigen-binding fragment of any of embodiments 293-363, provided that the antibody or antigen-binding fragment specifically binds to human TL1A. 365. The antibody or antigen-binding fragment of embodiment 364, provided that the antibody or antigen-binding fragment specifically binds to human TL1A with a Kg of 1x10 M or less. 366. The antibody or antigen-binding fragment of embodiment 365, provided that the Kq is measured using a method selected from a standard ELISA assay and SPR. 367. The antibody or antigen-binding fragment of any of embodiments 293-366, provided that the antibody or antigen-binding fragment inhibits binding of DR3 to human TL1A. 368. The antibody or antigen-binding fragment of any of embodiments 293-367, provided that the antibody or antigen-binding fragment inhibits binding of DcR3 to human TL1A. 369. The antibody or antigen-binding fragment of any of embodiments 293-368, provided that the antibody or antigen-binding fragment is a humanized antibody, a CDR-grafted antibody, a chimeric antibody, a Fab, a ScFv, or a combination thereof. 370. The antibody or antigen-binding fragment of any of embodiments 293-369, comprising a human CHI domain. 371. The antibody or antigen-binding fragment of any of embodiments 293-370, comprising a human CH?2 domain. 372. The antibody or antigen-binding fragment of embodiment 371, provided that that CH2 domain comprises at least one mutation selected from L234A, L235A, and G237A, as numbered using Kabat. 373. The antibody or antigen-binding fragment of any of embodiments 293-372, comprising a human CH3 domain. 374. A pharmaceutical composition comprising a therapeutically effective amount of the antibody or antigen-binding fragment of any of embodiments 293-373, and a pharmaceutically acceptable carrier. 375. A method of treating an inflammatory disease in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the antibody or antigen- binding fragment of any of embodiments 293-373. 376. The method of embodiment 375, provided that the inflammatory disease is inflammatory bowel disease. 377. The method of embodiment 376, provided that the inflammatory bowel disease comprises Crohn’s disease. 378. The method of embodiment 377, provided that the subject has been determined to be non- responsive to anti-TNF alpha therapy. 379. The method of embodiment 377 or embodiment 378, provided that the subject has been determined to comprise a disease phenotype comprising non-stricturing / non-penetrating, stricturing, stricturing and penetrating, or isolated internal penetrating, 380. An antibody or antigen-binding fragment that specifically binds to TL1A, comprising: a heavy chain variable region comprising three heavy chain complementarity-determining regions (HCDR1, HCDR2, and HCDR3) comprising (a) a HCDR1 selected from: (i) a HCDR1 comprising SEQ ID NO: 1009, (ii) a HCDRI1 comprising SEQ ID NO: 100150, wherein Xj is selected from D and E, Xs is selected from I, P and V, X; is selected from G, Q, S, and V, Xs is selected from F and Y, and Xs is selected from I and M, (iii) a HCDR1 selected from SEQ ID NOS: 100200-100295, and (iv) a HCDR1 comprising an amino acid sequence that differs from a sequence selected from the group consisting of SEQ ID NOS: 1009, 100150 and 100200-100295 by up to five, four, three, or two amino acids, (b) a HCDR2 selected from: (i) a HCDR2 comprising SEQ ID NO: 10012, and (ii) a HCDR2 comprising an amino acid sequence that differs from SEQ ID NO: 10012 by up to five, four, three, or two amino acids, and (©) a HCDR3 selected from (i) a HCDR3 comprising SEQ ID NO: 10015, (ii) a HCDR3 comprising SEQ ID NO: 100152, wherein Xj is selected from L and M, and X; is selected from E, LK, L,M, Q, T, V, W, and Y, (iii) a HCDR3 selected from SEQ ID NOS: 100296-100314, and (iv) a HCDR3 comprising an amino acid sequence that differs from a sequence selected from the group consisting of SEQ ID NOS: 10015, 100152 and 100296-100314 by up to five, four, three, or two amino acids; and a light chain variable region comprising three light chain complementarity-determining regions (LCDR1, LCDR2, and LCDR3) comprising: (a) a LCDRI selected from: (i) a LCDR1 comprising SEQ ID NO: 10018, and (ii) a LCDRI comprising an amino acid sequence that differs from SEQ ID NO: 10018 by up to five, four, three, or two amino acids, (b) a LCDR2 selected from: (i) a LCDR2 comprising SEQ ID NO: 10021, and (ii) a LCDR2 comprising an amino acid sequence that differs from SEQ ID NO: 10021 by up to five, four, three, or two amino acids, and (©) a LCDR3 selected from (i) a LCDR3 comprising SEQ ID NO: 10024, (ii) a LCDR3 comprising SEQ ID NO: 100155, wherein X is selected from Q and N, X; is selected from D, E, H, N, Q, and S, X; is selected from A and G, and Xs is selected from D, F, K, N, R, S, and T, (iii) a LCDR3 selected from SEQ ID NOS: 100315-100482, and (iv) a LCDR3 comprising an amino acid sequence that differs from a sequence selected from the group consisting of SEQ ID NOS: 10024, 100155, and 100315-100482 by up to five, four, three, or two amino acids. 381. The antibody or antigen-binding fragment of embodiment 380, provided that the HCDR1 comprises SEQ ID NO: 100150, the HCDR2 comprises SEQ ID NO: 10012, the HCDR3 comprises SEQ ID NO: 100152, the LCDR1 comprises SEQ ID NO: 10018, the LCDR2 comprises SEQ ID NO: 10021, and the LCDR3 comprises SEQ ID NO: 100155. 382. The antibody or antigen-binding fragment of embodiment 380 or embodiment 381, provided that the X; of SEQ ID NO: 100150 is D. 383. The antibody or antigen-binding fragment of embodiment 380 or embodiment 381 provided that the X; of SEQ ID NO: 100150 is E. 384. The antibody or antigen-binding fragment of any of embodiments 380-383, provided that the X> of SEQ ID NO: 100150 is I. 385. The antibody or antigen-binding fragment of any of embodiments 380-383, provided that the X3 of SEQ ID NO: 100150 is P. 386. The antibody or antigen-binding fragment of any of embodiments 380-383, provided that the X3 of SEQ ID NO: 100150is V. 387. The antibody or antigen-binding fragment of any of embodiments 380-386, provided that the X3 of SEQ ID NO: 1001501is G. 388. The antibody or antigen-binding fragment of any of embodiments 380-386, provided that the X3 of SEQ ID NO: 1001501is Q. 389. The antibody or antigen-binding fragment of any of embodiments 380-386, provided that the X3 of SEQ ID NO: 1001501is S. 390. The antibody or antigen-binding fragment of any of embodiments 380-386, provided that the X3 of SEQ ID NO: 100150is V. 391. The antibody or antigen-binding fragment of any of embodiments 380-390, provided that the Xs of SEQ ID NO: 100150 is F. 392. The antibody or antigen-binding fragment of any of embodiments 380-390, provided that the Xs of SEQ ID NO: 100150is Y. 393. The antibody or antigen-binding fragment of any of embodiments 380-392, provided that the Xs of SEQ ID NO: 1001501is I. 394. The antibody or antigen-binding fragment of any of embodiments 380-392, provided that the Xs of SEQ ID NO: 100150 is M. 395. The antibody or antigen-binding fragment of any of embodiments 380-394, provided that the X; of SEQ ID NO: 100152 is L. 396. The antibody or antigen-binding fragment of any of embodiments 380-394, provided that the X) of SEQ ID NO: 100152 is M. 397. The antibody or antigen-binding fragment of any of embodiments 380-396, provided that the X> of SEQ ID NO: 100152 is E. 398. The antibody or antigen-binding fragment of any of embodiments 380-396, provided that the X; of SEQ ID NO: 100152 is I. 399. The antibody or antigen-binding fragment of any of embodiments 380-396, provided that the X3 of SEQ ID NO: 100152 is K. 400. The antibody or antigen-binding fragment of any of embodiments 380-396, provided that the X> of SEQ ID NO: 100152 is L. 401. The antibody or antigen-binding fragment of any of embodiments 380-396, provided that the Xz of SEQ ID NO: 100152 is M. 402. The antibody or antigen-binding fragment of any of embodiments 380-396, provided that the X3 of SEQ ID NO: 100152 is Q. 403. The antibody or antigen-binding fragment of any of embodiments 380-396, provided that the X3 of SEQ ID NO: 100152 is T. 404. The antibody or antigen-binding fragment of any of embodiments 380-396, provided that the Xz of SEQ ID NO: 100152is V. 405. The antibody or antigen-binding fragment of any of embodiments 380-396, provided that the Xo of SEQ ID NO: 100152 is W. 406. The antibody or antigen-binding fragment of any of embodiments 380-396, provided that the X; of SEQ ID NO: 100152is Y. 407. The antibody or antigen-binding fragment of any of embodiments 380-406, provided that the X; of SEQ ID NO: 100155is Q. 408. The antibody or antigen-binding fragment of any of embodiments 380-406, provided that the X) of SEQ ID NO: 100155 is N. 409. The antibody or antigen-binding fragment of any of embodiments 380-408, provided that the Xz of SEQ ID NO: 100155is D. 410. The antibody or antigen-binding fragment of any of embodiments 380-408, provided that the X3 of SEQ ID NO: 100155is E. 411. The antibody or antigen-binding fragment of any of embodiments 380-408, provided that the X; of SEQ ID NO: 100155 is H. 412. The antibody or antigen-binding fragment of any of embodiments 380-408, provided that the X> of SEQ ID NO: 100155 is N. 413. The antibody or antigen-binding fragment of any of embodiments 380-408, provided that the Xz of SEQ ID NO: 100155is Q. 414. The antibody or antigen-binding fragment of any of embodiments 380-408, provided that the X> of SEQ ID NO: 1001551is S. 415. The antibody or antigen-binding fragment of any of embodiments 380-414, provided that the X3 of SEQ ID NO: 100155 is A. 416. The antibody or antigen-binding fragment of any of embodiments 380-414, provided that the X3 of SEQ ID NO: 100155is G. 417. The antibody or antigen-binding fragment of any of embodiments 380-416, provided that the Xs of SEQ ID NO: 100155is D. 418. The antibody or antigen-binding fragment of any of embodiments 380-416, provided that the Xs of SEQ ID NO: 100155is F. 419. The antibody or antigen-binding fragment of any of embodiments 380-416, provided that the Xs of SEQ ID NO: 100155is K. 420. The antibody or antigen-binding fragment of any of embodiments 380-416, provided that the Xs of SEQ ID NO: 100155 is N. 421. The antibody or antigen-binding fragment of any of embodiments 380-416, provided that the Xs of SEQ ID NO: 100155is R. 422. The antibody or antigen-binding fragment of any of embodiments 380-416, provided that the Xs of SEQ ID NO: 1001551is S. 423. The antibody or antigen-binding fragment of any of embodiments 380-416, provided that the Xs of SEQ ID NO: 100155is T. 424. The antibody or antigen-binding fragment of any of embodiments 380-423, provided that the antibody or antigen-binding fragment specifically binds to human TL1A. 425. The antibody or antigen-binding fragment of embodiment 424, provided that the antibody or antigen-binding fragment specifically binds to human TLI1A with a Kg of 1x10° M or less. 426. The antibody or antigen-binding fragment of embodiment 425, provided that the Kq is measured using a method selected from a standard ELISA assay and SPR. 427. The antibody or antigen-binding fragment of any of embodiments 380-426, provided that the antibody or antigen-binding fragment inhibits binding of DR3 to human TL1A. 428. The antibody or antigen-binding fragment of any of embodiments 380-427, provided that the antibody or antigen-binding fragment inhibits binding of DcR3 to human TL1A. 429. The antibody or antigen-binding fragment of any of embodiments 380-428, provided that the antibody or antigen-binding fragment is a humanized antibody, a CDR-grafted antibody, a chimeric antibody, a Fab, a ScFv, or a combination thereof. 430. The antibody or antigen-binding fragment of any of embodiments 380-429, comprising a human CH1 domain. 431. The antibody or antigen-binding fragment of any of embodiments 380-430, comprising a human CH?2 domain. 432. The antibody or antigen-binding fragment of embodiment 431, provided that that CH2 domain comprises at least one mutation selected from L234A, L235A, and G237A, as numbered using Kabat, 433, The antibody or antigen-binding fragment of any of embodiments 380-432, comprising a human CH3 domain. 434. A pharmaceutical composition comprising a therapeutically effective amount of the antibody or antigen-binding fragment of any of embodiments 380-433, and a pharmaceutically acceptable carrier. 435. A method of treating an inflammatory disease in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the antibody or antigen- binding fragment of any of embodiments 380-433. 436. The method of embodiment 435, provided that the inflammatory disease is inflammatory bowel disease. 437. The method of embodiment 436, provided that the inflammatory bowel disease comprises Crohn’s disease. 438. The method of embodiment 437, provided that the subject has been determined to be non- responsive to anti-TNF alpha therapy. 439. The method of embodiment 437 or embodiment 438, provided that the subject has been determined to comprise a disease phenotype comprising non-stricturing / non-penetrating, stricturing, stricturing and penetrating, or isolated internal penetrating, 440. An antibody or antigen-binding fragment that specifically binds to TL1A, comprising: a heavy chain variable region comprising SEQ ID NO: 10052 or SEQ ID NO: 10054, and a light chain variable region comprising SEQ ID NO: 10053. 441. The antibody or antigen-binding fragment of embodiment 440, provided that the heavy chain variable region comprises SEQ ID NO: 10052. 442. The antibody or antigen-binding fragment of embodiment 440, provided that the heavy chain variable region comprises SEQ ID NO: 10054. 443, The antibody or antigen-binding fragment of any of embodiments 440-442, provided that the X; of SEQ ID NO: 10052 or SEQ ID NO: 10054 is D. 444. The antibody or antigen-binding fragment of any of embodiments 440-442 provided that the X; of SEQ ID NO: 10052 or SEQ ID NO: 10054 is E. 445. The antibody or antigen-binding fragment of any of embodiments 440-444, provided that the Xz of SEQ ID NO: 10052 or SEQ ID NO: 10054 is I. 446. The antibody or antigen-binding fragment of any of embodiments 440-444, provided that the Xz of SEQ ID NO: 10052 or SEQ ID NO: 10054 is P. 447. The antibody or antigen-binding fragment of any of embodiments 440-444, provided that the Xz of SEQ ID NO: 10052 or SEQ ID NO: 10054 is V. 448. The antibody or antigen-binding fragment of any of embodiments 440-447, provided that the X3 of SEQ ID NO: 10052 or SEQ ID NO: 10054 is G. 449. The antibody or antigen-binding fragment of any of embodiments 440-447, provided that the X3 of SEQ ID NO: 10052 or SEQ ID NO: 10054 is Q. 450. The antibody or antigen-binding fragment of any of embodiments 440-447, provided that the X3 of SEQ ID NO: 10052 or SEQ ID NO: 10054 is S. 451. The antibody or antigen-binding fragment of any of embodiments 440-447, provided that the X3 of SEQ ID NO: 10052 or SEQ ID NO: 10054 is V. 452. The antibody or antigen-binding fragment of any of embodiments 440-451, provided that the Xs of SEQ ID NO: 10052 or SEQ ID NO: 10054 is F. 453. The antibody or antigen-binding fragment of any of embodiments 440-451, provided that the X4 of SEQ ID NO: 10052 or SEQ ID NO: 10054 is Y. 454. The antibody or antigen-binding fragment of any of embodiments 440-453, provided that the Xs of SEQ ID NO: 10052 or SEQ ID NO: 10054 is I. 455. The antibody or antigen-binding fragment of any of embodiments 440-453, provided that the Xs of SEQ ID NO: 10052 or SEQ ID NO: 10054 is M. 456. The antibody or antigen-binding fragment of any of embodiments 440-455, provided that the Xs of SEQ ID NO: 10052 or SEQ ID NO: 10054 is L. 457. The antibody or antigen-binding fragment of any of embodiments 440-455, provided that the Xs of SEQ ID NO: 10052 or SEQ ID NO: 10054 is M. 458. The antibody or antigen-binding fragment of any of embodiments 440-457, provided that the X7 of SEQ ID NO: 10052 or SEQ ID NO: 10054 is E. 459. The antibody or antigen-binding fragment of any of embodiments 440-457, provided that the X7 of SEQ ID NO: 10052 or SEQ ID NO: 10054 is I. 460. The antibody or antigen-binding fragment of any of embodiments 440-457, provided that the X7 of SEQ ID NO: 10052 or SEQ ID NO: 10054 is K. 461. The antibody or antigen-binding fragment of any of embodiments 440-457, provided that the X7 of SEQ ID NO: 10052 or SEQ ID NO: 10054 is L. 462. The antibody or antigen-binding fragment of any of embodiments 440-457, provided that the X7 of SEQ ID NO: 10052 or SEQ ID NO: 10054 is M. 463. The antibody or antigen-binding fragment of any of embodiments 440-457, provided that the X7 of SEQ ID NO: 10052 or SEQ ID NO: 10054 is Q. 464. The antibody or antigen-binding fragment of any of embodiments 440-457, provided that the X7 of SEQ ID NO: 10052 or SEQ ID NO: 10054 is T. 465. The antibody or antigen-binding fragment of any of embodiments 440-457, provided that the X7 of SEQ ID NO: 10052 or SEQ ID NO: 10054 is V. 466. The antibody or antigen-binding fragment of any of embodiments 440-457, provided that the X7 of SEQ ID NO: 10052 or SEQ ID NO: 10054 is W. 467. The antibody or antigen-binding fragment of any of embodiments 440-457, provided that the X7 of SEQ ID NO: 10052 or SEQ ID NO: 10054 is Y. 468. The antibody or antigen-binding fragment of any of embodiments 440-467, provided that the X; of SEQ ID NO: 10053 is Q. 469. The antibody or antigen-binding fragment of any of embodiments 440-467, provided that the X; of SEQ ID NO: 10053 is N. 470. The antibody or antigen-binding fragment of any of embodiments 440-469, provided that the X3 of SEQ ID NO: 10053 is D. 471. The antibody or antigen-binding fragment of any of embodiments 440-469, provided that the X3 of SEQ ID NO: 10053 is E. 472. The antibody or antigen-binding fragment of any of embodiments 440-469, provided that the X> of SEQ ID NO: 10053 is H. 473. The antibody or antigen-binding fragment of any of embodiments 440-469, provided that the X> of SEQ ID NO: 10053 is N. 474. The antibody or antigen-binding fragment of any of embodiments 440-469, provided that the X; of SEQ ID NO: 10053 is Q. 475. The antibody or antigen-binding fragment of any of embodiments 440-469, provided that the X; of SEQ ID NO: 10053 is S. 476. The antibody or antigen-binding fragment of any of embodiments 440-475, provided that the X3 of SEQ ID NO: 10053 is A. 477. The antibody or antigen-binding fragment of any of embodiments 440-475, provided that the X3 of SEQ ID NO: 10053 is G. 478. The antibody or antigen-binding fragment of any of embodiments 440-477, provided that the Xs of SEQ ID NO: 10053 is D. 479. The antibody or antigen-binding fragment of any of embodiments 440-477, provided that the Xs of SEQ ID NO: 10053 is F. 480. The antibody or antigen-binding fragment of any of embodiments 440-477, provided that the X4 of SEQ ID NO: 10053 is K. 481. The antibody or antigen-binding fragment of any of embodiments 440-477, provided that the Xs of SEQ ID NO: 10053 is N. 482. The antibody or antigen-binding fragment of any of embodiments 440-477, provided that the Xs of SEQ ID NO: 10053 is R. 483. The antibody or antigen-binding fragment of any of embodiments 440-477, provided that the Xs of SEQ ID NO: 10053 is S. 484. The antibody or antigen-binding fragment of any of embodiments 440-477, provided that the Xs of SEQ ID NO: 10053 is T. 485. An antibody or antigen-binding fragment that specifically binds to TL1A, comprising: a heavy chain variable region of SEQ ID NO: 10036, and a light chain variable region of SEQ ID NO: 10038. 486. An antibody or antigen-binding fragment that specifically binds to TL1A, comprising: a heavy chain variable region of SEQ ID NO: 10040, and a light chain variable region of SEQ ID NO: 10042. 487. An antibody or antigen-binding fragment that specifically binds to TL1A, comprising; a heavy chain variable region of SEQ ID NO: 10040, and a light chain variable region of SEQ ID NO: 10038. 488. An antibody or antigen-binding fragment that specifically binds to TL1A, comprising: a heavy chain variable region of SEQ ID NO: 10044, and a light chain variable region of SEQ ID NO: 10038. 489. An antibody or antigen-binding fragment that specifically binds to TL1A, comprising: a heavy chain variable region of SEQ ID NO: 10043, and a light chain variable region of SEQ ID NO: 10038. 490. An antibody or antigen-binding fragment that specifically binds to TL1A, comprising: a heavy chain variable region of SEQ ID NO: 10045, and a light chain variable region of SEQ ID NO: 10038. 491. An antibody or antigen-binding fragment that specifically binds to TL1A, comprising: a heavy chain variable region of SEQ ID NO: 10046, and a light chain variable region of SEQ ID NO: 10038. 492. An antibody or antigen-binding fragment that specifically binds to TL1A, comprising: a heavy chain variable region of SEQ ID NO: 10040, and a light chain variable region of SEQ ID NO: 10047. 493. An antibody or antigen-binding fragment that specifically binds to TL1A, comprising: a heavy chain variable region of SEQ ID NO: 10040, and a light chain variable region of SEQ ID NO: 10048. 494. An antibody or antigen-binding fragment that specifically binds to TL1A, comprising: a heavy chain variable region of SEQ ID NO: 10040, and a light chain variable region of SEQ ID NO: 10049. 495. An antibody or antigen-binding fragment that specifically binds to TL1A, comprising: a heavy chain variable region of SEQ ID NO: 10040, and a light chain variable region of SEQ ID NO: 10050. 496. An antibody or antigen-binding fragment that specifically binds to TL1A, comprising: a heavy chain variable region of SEQ ID NO: 10040, and a light chain variable region of SEQ ID NO: 10051. 497. The antibody or antigen-binding fragment of any of embodiments 440-496, provided that the antibody or antigen-binding fragment specifically binds to human TL1A. 498. The antibody or antigen-binding fragment of embodiment 497, provided that the antibody or antigen-binding fragment specifically binds to human TL1A with a Kg of 1x10 M or less. 499. The antibody or antigen-binding fragment of embodiment 498, provided that the Kq is measured using a method selected from a standard ELISA assay and SPR. 500. The antibody or antigen-binding fragment of any of embodiments 440-499, provided that the antibody or antigen-binding fragment inhibits binding of DR3 to human TL1A. 501. The antibody or antigen-binding fragment of any of embodiments 440-500, provided that the antibody or antigen-binding fragment inhibits binding of DcR3 to human TL1A. 502. The antibody or antigen-binding fragment of any of embodiments 440-501, provided that the antibody or antigen-binding fragment is a humanized antibody, a CDR-grafted antibody, a chimeric antibody, a Fab, a ScFv, or a combination thereof. 503. The antibody or antigen-binding fragment of any of embodiments 440-502, comprising a human CHI domain. 504. The antibody or antigen-binding fragment of any of embodiments 440-503, comprising a human CH2 domain. 505. The antibody or antigen-binding fragment of embodiment 504, provided that that CH2 domain comprises at least one mutation selected from L234A, L235A, and G237A, as numbered using Kabat. 506. The antibody or antigen-binding fragment of any of embodiments 440-505, comprising a human CH3 domain. 507. A pharmaceutical composition comprising a therapeutically effective amount of the antibody or antigen-binding fragment of any of embodiments 440-506, and a pharmaceutically acceptable carrier. 508. A method of treating an inflammatory disease in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the antibody or antigen- binding fragment of any of embodiments 440-506. 509. The ...

Claims

CLAIMS WHAT IS CLAIMED: I A method of treating an inflammatory, a fibrotic, or a fibrostenotic disease or condition in a subject, the method comprising administering to the subject a therapeutically effective amount of an inhibitor of Tumor necrosis factor-like cytokine 1A (TL1A) activity or expression, provided at least three polymorphisms comprising rs1892231, 1556124762, 156478109, rs2070558, rs2070561, rs11897732, rs6740739, rs17796285, rs7935393, 1512934476, rs12457255, rs2070557, rs4246905, rs10974900, rs12434976, rs16901748, 152815844, rs889702, rs2409750, rs1541020, rs4942248. rs12934476, rs12457255, 152297437, rs41309367, rs10733509, rs10750376, rs10932456, rs1326860, rs1528663, 15951279, rs9806914, rs7935393, 151690492, rs420726, rs7759385, rs10974900, 151326860, 152548147, 152815844, rs889702, rs9806914, rs7278257, orrs11221332. ora proxy polymorphism in linkage disequilibrium therewith as determined with an R? of at least 0.85, or a combination thereof, are detected in a sample obtained from the subject.

2. The method of claim 1, wherein the at least three polymorphisms are predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression at a positive predictive value of at least about 70%.

3. The method of claim 1, wherein the at least three polymorphisms are predictive of positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a specificity of at least about 70%. 4, The method of claim 1, wherein the at least three polymorphisms comprise: (a) rs6478109, rs56124762, and rs1892231; (b) rs6478109, rs56124762, and rs16901748; (c) rs6478109, rs1892231, and 1516901748; (d) rs56124762, 151892231, and rs16901748; (e) rs6478109, rs2070558, and rs1892231; (f) rs6478109, rs2070558, and rs16901748; (g) rs6478109, rs1892231, and 516901748; (h) rs2070558, rs1892231, and 1516901748; (i) rs6478109, rs2070561, and rs1892231; (4) rs6478109, rs2070561 , and rs16901748; (k) rs6478109, rs1892231, and 1516901748; (1) rs2070561, rs1892231, and 1516901748; (m)rs6478109, rs7935393, and rs1892231; (n) rs6478109, rs7935393, and rs9806914; (0) rs6478109, rs7935393, and rs7278257; (p) rs6478109, rs7935393, and rs2070557; (q) rs6478109, rs1892231, and rs9806914; (r) rs6478109, rs1892231, and rs7278257; (s) rs6478109, rs1892231, and rs2070557; (t) rs6478109, rs9806914, and rs7278257; (u) rs6478109, rs9806914, and rs2070557; (Vv) rs6478109, rs7278257, and rs2070557; (w)rs7935393, rs1892231, and rs9806914; (x) rs7935393, rs1892231, and rs7278257; (y) rs7935393, rs1892231, and rs2070557; (z) rs7935393, rs9806914, and rs7278257; (aa) 157935393, rs9806914, and rs2070557; (bb) 157935393, rs7278257, and rs2070557; (cc) rs1892231, rs9806914, and rs7278257; (dd) 151892231, rs9806914, and rs2070557; (ee) rs1892231, rs7278257, and rs2070557; or (ff) rs9806914, rs7278257, and rs2070557. The method of claim 1, wherein the at least three polymorphisms further comprises a fourth polymorphism comprising rs16901748, rs1892231, rs56124762, rs6478109, 152070558, 152070561, rs11897732, 156740739, 1817796285, 137935393, rs12934476, 1512457255, rs2070557, rs4246905, rs10974900, rs12434976, 152815844, rs889702, 152409750, 151541020, rs4942248, 1512934476, 1312457255, rs2297437, rs41309367, 1510733509, rs10750376, rs10932456, rs1326860, 151528663, 15951279, rs9806914, 157935393, rs1690492, rs420726, 157759385, rs10974900, rs1326860, rs2548147, 152815844, 1s889702, rs9806914, 157278257, or rs11221332, or a proxy polymorphism in linkage disequilibrium therewith as determined with an R? of at least 0.85, or a combination thereof 6. The method of method of claim 1, wherein the at least three polymorphisms are detected in the sample by subjecting the sample to an assay configured to detect a presence of at least three nucleotides corresponding to nucleic acid position 501 within at least three of SEQ ID NOS: 1-41, or 57-59.

7. The method of claim 1, wherein the inflammatory, fibrotic, or fibrostenotic disease or condition comprises inflammatory bowel disease, Crohn’s disease, obstructive Crohn’s disease, ulcerative colitis, intestinal fibrosis, intestinal fibrostenosis, rheumatoid arthritis, or primary sclerosing cholangitis.

8. The method of claim 7, wherein the Crohn’s disease is ileal, ileocolonic, or colonic Crohn’s disease.

9. The method of claim 1, wherein the subject has, or is at risk for developing, a non- response or loss-of-response to a standard therapy comprising glucocorticosteriods, anti- TNF therapy, anti-a4-b7 therapy, anti-IL12p40 therapy, or a combination thereof.

10. The method of claim 1, wherein the inhibitor of TL1A is an anti-TL1A antibody or antigen-binding fragment.

11. A method of treating an inflammatory, a fibrotic, or a fibrostenotic disease or condition in a subject, the method comprising: (a) determining whether the subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition is suitable for treatment with an inhibitor of TL1A activity or expression by: (i) obtaining or having obtained a sample from the subject; and (ii) subjecting the sample to an assay adapted to detect at least three polymorphisms comprising rs1892231, rs56124762, rs6478109, rs2070558, 152070561, rs11897732, rs6740739, rs17796285, 157935393, 1512934476, rs12457255, 152070557, rs4246905, rs10974900, rs12434976, rs16901748, 152815844, rs889702, 152409750, rs1541020, rs4942248, rs12934476, rs12457255, 152297437, rs41309367, rs10733509, rs10750376, rs10932456, rs1326860, rs1528663, rs951279, rs9806914, rs7935393, rs1690492, 15420726, 157759385, 1510974900, rs1326860, rs2548147, rs2815844, rs889702, rs9806914, rs7278257, rs11221332, or a proxy polymorphism in linkage disequilibrium therewith as determined with an R? of at least 0.85, or a combination thereof: and (b) treating the subject by administering a therapeutically effective amount of the inhibitor of TL1A activity or expression to the subject.

12. The method of claim 11, wherein the at least three polymorphisms are predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression at a positive predictive value of at least about 70%.

13. The method of claim 11, wherein the at least three polymorphisms are predictive of a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression at a specificity of at least about 70%.

14. The method of claim 11, wherein the inflammatory, fibrotic, or fibrostenotic disease or condition comprises inflammatory bowel disease, Crohn’s disease, obstructive Crohn’s disease, ulcerative colitis, intestinal fibrosis, intestinal fibrostenosis, rheumatoid arthritis, or primary sclerosing cholangitis.

15. The method of claim 14, wherein the Crohn’s disease is ileal, ileocolonic, or colonic Crohn’s disease.

16. The method of claim 11, wherein the wherein the inhibitor of TL1A activity or expression is an anti-TL1A antibody or antigen-binding fragment.

17. The method of claim 11, wherein the at least three polymorphisms comprise: (a) rs6478109, rs56124762, and rs1892231; (b) rs6478109, rs56124762, and rs16901748; (c) rs6478109, rs1892231, and 516901748; (d) rs56124762, 151892231, and rs16901748; (e) rs6478109, rs2070558, and rs1892231; (f) rs6478109, rs2070558, and 1516901748; (g) rs6478109, rs1892231, and rs16901748; (h) rs2070558, rs1892231, and 1516901748; (i) rs6478109, rs2070561, and rs1892231; (4) rs6478109, rs2070561 , and rs16901748; (k) rs6478109, rs1892231, and rs16901748; (1) rs2070561, rs1892231, and 1516901748; (m)rs6478109, rs7935393, and rs1892231; (n) rs6478109, rs7935393, and rs9806914; (0) rs6478109, rs7935393, and rs7278257; (p) rs6478109, rs7935393, and rs2070557; (q) rs6478109, rs1892231, and rs9806914; (r) rs6478109, rs1892231, and rs7278257; (s) rs6478109, rs1892231, and rs2070557; (t) rs6478109, rs9806914, and rs7278257; (u) rs6478109, rs9806914, and rs2070557; (Vv) rs6478109, rs7278257, and rs2070557; (w)rs7935393, rs1892231, and rs9806914; (x) rs7935393, rs1892231, and rs7278257; (y) rs7935393, rs1892231, and rs2070557; (z) rs7935393, rs9806914, and rs7278257; (aa) 157935393, rs9806914, and rs2070557; (bb) 157935393, rs7278257, and rs2070557; (cc) rs1892231, rs9806914, and rs7278257; (dd) 151892231, rs9806914, and rs2070557; (ee) rs1892231, rs7278257, and rs2070557; or (ff) rs9806914, rs7278257, and rs2070557.

18. The method of claim 11, wherein the at least three polymorphisms further comprises a fourth polymorphism comprising 1516901748, rs1892231, rs56124762, rs6478109, 152070558, 152070561, 1511897732, 156740739, rs17796285, rs7935393, rs12934476, 1512457255, rs2070557, rs4246905, rs10974900, rs12434976, rs2815844, rs889702, 152409750, rs1541020, rs4942248, rs12934476, 1312457255, rs2297437, rs41309367, 1510733509, rs10750376, rs10932456, rs1326860, rs1528663, rs951279, rs9806914, 157935393, 51690492, 15420726, rs7759385, rs10974900, rs1326860, rs2548147, 152815844, 15889702, rs9806914, rs7278257, or rs11221332 or a proxy polymorphism in linkage disequilibrium therewith as determined with an R2 of at least 0.85, or a combination thereof 19. The method of claim 11, wherein the subject is at risk of developing a non-response or loss-of-response to a standard therapy comprising glucocorticosteriods, anti-TNF therapy, anti-a4-b7 therapy, anti-IL12p40 therapy, or a combination thereof. 20; A method of treating an inflammatory, a fibrotic, or a fibrostenotic disease or condition in a subject, the method comprising administering to the subject a therapeutically effective amount of an inhibitor of TL1A activity or expression, wherein the subject expresses at least three polymorphisms comprising rs16901748, rs6478109, rs56124762, or a proxy polymorphism in linkage disequilibrium therewith as determined with an R? of at least 0.85.

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