TL1a patient selection methods, systems, and devices

Abstract

SOLUTION: Provided are methods, systems, and kits for selecting a patient for treatment with a therapeutic agent based on the 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 an anti-TL1A antibody.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] Cross-reference 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.

[0002] Sequence Listing This application was electronically filed in ASCII format and includes a sequence listing that is hereby incorporated by reference in this specification. A copy of the ASCII, created on May 6, 2020, has a file name of 56884-761_601_SL.txt and a size of 14,467,905 bytes.

Background Art

[0003] A vast number of individuals are affected, and due to heterogeneous disease etiologies and various clinical symptoms, inflammatory diseases, fibrostenotic diseases, and fibrotic diseases pose a significant health burden worldwide. One such disease is inflammatory bowel disease (IBD), which has two common forms: Crohn's disease (CD) and ulcerative colitis (UC). IBD is a chronic relapsing inflammatory disorder of the gastrointestinal tract. The incidence of IBD is epidemic and affects nearly 3 million individuals in the United States alone.

[0004] The treatment options for patients with inflammatory, fibrostenotic, and fibrotic diseases are limited. Existing anti-inflammatory therapeutics such as steroids and tumor necrosis factor (TNF) inhibitors are commonly used as first-line treatments for IBD. Unfortunately, a significant number of patients experience a lack or loss of response to existing anti-inflammatory therapeutics, particularly TNF inhibitors. While patients are being treated with ineffective anti-inflammatory therapeutics, the disease worsens. Surgery, in the form of structureplasty (intestinal remodeling) or resection (intestinal removal), is the only treatment option for patients who do not respond to first-line treatment. Surgical treatment of IBD is invasive and causes postoperative risks in approximately one-third of patients undergoing surgery, such as anastomotic leakage, infections, and bleeding.

[0005] The etiology of inflammatory, fibrostenotic, and fibrotic diseases such as IBD is thought to involve an unregulated immune response that may be triggered by specific environmental factors in genetically susceptible individuals. The heterogeneity of the disease etiology and clinical course, combined with the various responses to treatment and its associated side effects, suggests that a personalized medical approach to treating these diseases is the best treatment strategy. However, there are very few personalized treatments available to patients. Therefore, it is necessary to identify targeted approaches for the treatment of inflammatory, fibrostenotic, and fibrotic diseases, as well as their subclinical phenotypes, and to develop reliable methods for identifying patients who may respond to a given treatment based on their genotype. The methods needed also identify controls who are not yet diagnosed but are at risk of progressing the disease. For this purpose, preventive interventions can be prescribed to reduce the increasing health burden.

[0006] Through genome-wide association studies (GWAS), researchers have been able to identify genetic variants (e.g., polymorphisms) significantly associated with IBD and its subclinical phenotypes. GWAS compare allele frequencies in a given population consisting of specific genetic variants between unrelated cases and controls, where cases represent affected individuals (e.g., IBD patients) and controls represent individuals without IBD. GWAS, Immunochip, and their meta-analyses have enabled the discovery of over 200 polymorphisms associated with IBD, including CD and UC.

[0007] The first GWAS on IBD identified TNFSF15 as an IBD locus encompassing various polymorphisms associated with IBD. The TNFSF15 protein, also known as TL1A, is a pro-inflammatory molecule that stimulates the proliferation and effector functions of Th1, Th2, and Th17 cells in the presence of TCR stimulation, in addition to CD8(+) cytotoxic T cells. TL1A bridges innate and adaptive immune responses, regulates adaptive immunity by increasing Th1, Th2, and Th17 effector cell functions, and is thought to be involved in the pathogenesis of IBD through T cell accumulation and immunopathology in inflamed tissues. In studies, IBD patients carrying specific risk alleles at the TNFSF15 locus have been demonstrated to show increased TNFSF15 (TL1A) expression and a higher likelihood of developing severe forms of IBD compared to individuals not carrying the risk allele. These findings suggest that inhibition of TL1A expression and / or activity may be a promising therapeutic strategy in various T cell-dependent autoimmune diseases, including IBD. These findings further suggest that the risk of increased TL1A expression and / or specific genotypes conferring severe forms of the disease in patients can be demonstrated to be useful for the prediction, diagnosis, and treatment of these individuals.

[0008] There are significant drawbacks to identifying therapeutic targets that are candidates for the treatment of a disease and methods of selecting patients for treatment based on GWAS alone. For example, GWAS is influenced by the linear polymorphism-phenotype associations between known risk loci and phenotypic traits and cannot capture high-dimensional non-linear polymorphism interactions such as the types of associations that reflect unknown biology. In addition, the effect sizes of individual polymorphisms identified using GWAS are often small in a given population. For this reason, polymorphisms identified by GWAS are not very effective in predicting sensitivity to complex diseases such as IBD (e.g., CD, UC). Furthermore, GWAS cannot convey or even constitute the biological mechanisms underlying the genetic associations between genetic mutations and phenotypic outcomes (e.g., IBD), rendering this mechanism ineffective in identifying therapeutic targets.

SUMMARY OF THE INVENTION

[0009] Disclosed herein are genotypes that are associated with and thus predict a positive treatment response in a subject or patient to an inhibitor of TL1A activity or expression (e.g., an anti-TL1A antibody) identified using a machine learning-based approach. The machine learning-based approach described herein enables the identification of combinations of polymorphisms and linear and non-linear interactions that more accurately predict the phenotypes of complex diseases such as IBD as compared to conventional GWAS alone. The genotypes described herein are associated with an increase in the level of TNFSF15 (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., from a normal individual). The genotypes disclosed herein are located in genes or loci that are directly or indirectly related to the TL1A-mediated or T cell-dependent inflammatory pathway. In addition, some of the genotypes provided herein are further significantly associated with inflammatory bowel disease (IBD) such as Crohn's disease (CD). This genotype is useful for selecting patients or subjects 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 the occurrence of clinical and subclinical phenotypes in a particular population of individuals are provided herein. For example, some of the genotypes of the present disclosure can be used to predict the risk that a subject will develop a TL1A-mediated inflammatory disease, a fibrostenotic disease, or a fibrotic disease. This genotype is further useful for predicting whether a patient diagnosed with an inflammatory, fibrotic, or fibrostenotic disease will progress to a severe form of the disease, such as a subclinical phenotype.

[0011] Furthermore, practical applications of the associations between the genotypes described herein include, but are not limited to, 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 that the patient or subject is a carrier of the genotype described herein. Additionally, or alternatively, practical applications of the associations between the genotypes disclosed herein and mutations in the expression of TNFSF15 (TL1A) are provided herein. Optionally, this genotype can be used to identify patients who may be suitable for treatment with a targeted TL1A therapy (e.g., patients who carry a genotype associated with increased TL1A may be suitable for treatment with an anti-TL1A therapy). An exemplary disease is Crohn's disease (CD). An exemplary inhibitor of TL1A activity or expression is an anti-TL1A antibody. In some examples, the anti-TL1A antibody is a neutralizing anti-TL1A antibody.

[0012] Aspects disclosed herein provide a method of treating an inflammatory, fibrotic, or fibrosing stenotic disorder or disease of interest, 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 that the presence of at least three polymorphisms is detected in a sample obtained from the subject, the at least three polymorphisms predicting that the subject will respond therapeutically to an inhibitor of TL1A with at least about 70% positive median rate. In some embodiments, the at least three polymorphisms are rs1892231, rs56124762, rs6478109, rs2070558, rs2070561, rs11897732, rs6740739, rs17796285, rs7935393, rs12934476, rs12457255, rs2070557, rs4246905, rs10974900, rs12434976, rs16901748, rs2815844, rs889702, rs2409750, rs1541020, rs4942248, rs12934476, rs12457255, rs2297437, rs41309367, rs10733509, rs10750376, rs10932456, rs1326860, rs1528663, rs951279, rs9806914, rs7935393, rs1690492, rs420726, rs7759385, rs10974900, rs1326860, rs2548147, rs2815844, rs889702, rs9806914, rs7278257, or rs11221332, or proxy polymorphisms that are in linkage disequilibrium with these, or combinations thereof, as determined by 2 2 including, or a combination thereof.

[0013] In some embodiments, at least three polymorphic forms are rs6478109, rs56124762, and rs1892231, rs6478109, rs56124762, and rs16901748, rs6478109, rs1892231, and rs16901748, rs56124762, rs1892231, and rs16901748, rs6478109, rs2070558, and rs1892231, rs6478109, rs2070558, and rs16901748, rs6478109, rs1892231, and rs16901748, rs2070558, rs1892231, and rs16901748, rs6478109, rs2070561, and rs1892231, rs6478109, rs2070561, and rs16901748, rs6478109, rs1892231, and rs16901748, rs2070561, rs1892231, and rs16901748, rs6478109, rs7935393, and rs1892231, rs6478109, rs7935393, and rs9806914, rs6478109, rs7935393, and rs7278257, rs6478109, rs7935393, and rs2070557, rs6478109, rs1892231, and rs9806914, rs6478109, rs1892231, and rs7278257, rs6478109, rs1892231, and rs2070557, rs6478109, rs9806914, and rs7278257, rs6478109, rs9806914, and rs2070557, rs6478109, rs7278257, and rs2070557, rs7935393, rs1892231, and rs9806914, rs7935393, rs1892231, and rs7278257, rs7935393, rs1892231, and rs2070557, rs7935393, rs9806914, and rs7278257, rs7935393, rs9806914, and rs2070557, rs7935393, rs7278257, and rs2070557, rs1892231, rs9806914, and rs7278257,It includes rs1892231, rs9806914, and rs2070557, rs1892231, rs7278257, and rs2070557, or rs9806914, rs7278257, and rs2070557. In some embodiments, at least three polymorphisms further include rs16901748, rs1892231, rs56124762, rs6478109, rs2070558, rs2070561, rs11897732, rs6740739, rs17796285, rs7935393, rs12934476, rs12457255, rs2070557, rs4246905, rs10974900, rs12434976, rs2815844, rs889702, rs2409750, rs1541020, rs4942248, rs12934476, rs12457255, rs2297437, rs41309367, rs10733509, rs10750376, rs10932456, rs1326860, rs1528663, rs951279, rs9806914, rs7935393, rs1690492, rs420726, rs7759385, rs10974900, rs1326860, rs2548147, rs2815844, rs889702, rs9806914, rs7278257, or rs11221332, or an R of at least 0.85. 2It includes a fourth polymorphism that is in linkage disequilibrium with these when determined by [[ID=]], or a combination thereof. In some embodiments, at least three polymorphisms include rs6478109, rs56124762, and rs1892231. In some embodiments, at least three polymorphisms include rs6478109, rs56124762, and rs16901748. In some embodiments, at least three polymorphisms include rs6478109, rs1892231, and rs16901748. In some embodiments, at least three polymorphisms include rs6478109, rs1892231, and rs16901748. In some embodiments, the proxy polymorphisms in linkage disequilibrium are independently associated with a clinical phenotype associated with an inflammatory, fibrotic, or fibrostrictive disease or disorder of interest. In some embodiments, the clinical phenotype is a stricturing and penetrating disease.

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

[0015] In some embodiments, at least three polymorphisms are detected in a sample by subjecting the sample to an assay configured to detect the 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 includes polymerase chain reaction (PCR), quantitative reverse transcription PCR (qPCR), automated sequencing, or a genotyping array.

[0016] In some embodiments, the inflammatory, fibrotic, or fibrosing disorder or disease includes 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, Crohn's disease is Crohn's disease of the ileum, ileocolon, or colon. In some embodiments, the subject exhibits non-response or loss of response to, or is at risk of progressing, to standard therapeutic agents including glucocorticosteroids, anti-TNF therapeutic agents, anti-a4-b7 therapeutic agents, anti-IL12p40 therapeutic agents, or combinations 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 human TL1A in the same region as a reference antibody selected from Table 2. In some embodiments, the method further includes administering an additional therapeutic agent to the subject.

[0017] Aspects disclosed herein provide a method of treating an inflammatory, fibrotic, or fibrostrictive disorder or disease of interest, 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 that at least three polymorphisms, including a proxy polymorphism in linkage disequilibrium with these when determined by 2 2 or a combination thereof, are detected in a sample obtained from the subject.

[0018] In some embodiments, at least three polymorphic forms are rs6478109, rs56124762, and rs1892231, rs6478109, rs56124762, and rs16901748, rs6478109, rs1892231, and rs16901748, rs56124762, rs1892231, and rs16901748, rs6478109, rs2070558, and rs1892231, rs6478109, rs2070558, and rs16901748, rs6478109, rs1892231, and rs16901748, rs2070558, rs1892231, and rs16901748, rs6478109, rs2070561, and rs1892231, rs6478109, rs2070561, and rs16901748, rs6478109, rs1892231, and rs16901748, rs2070561, rs1892231, and rs16901748, rs6478109, rs7935393, and rs1892231, rs6478109, rs7935393, and rs9806914, rs6478109, rs7935393, and rs7278257, rs6478109, rs7935393, and rs2070557, rs6478109, rs1892231, and rs9806914, rs6478109, rs1892231, and rs7278257, rs6478109, rs1892231, and rs2070557, rs6478109, rs9806914, and rs7278257, rs6478109, rs9806914, and rs2070557, rs6478109, rs7278257, and rs2070557, rs7935393, rs1892231, and rs9806914, rs7935393, rs1892231, and rs7278257, rs7935393, rs1892231, and rs2070557, rs7935393, rs9806914, and rs7278257, rs7935393, rs9806914, and rs2070557, rs7935393, rs7278257, and rs2070557, rs1892231, rs9806914, and rs7278257,It includes rs1892231, rs9806914, and rs2070557, rs1892231, rs7278257, and rs2070557, or rs9806914, rs7278257, and rs2070557. In some embodiments, at least three polymorphisms further include rs16901748, rs1892231, rs56124762, rs6478109, rs2070558, rs2070561, rs11897732, rs6740739, rs17796285, rs7935393, rs12934476, rs12457255, rs2070557, rs4246905, rs10974900, rs12434976, rs2815844, rs889702, rs2409750, rs1541020, rs4942248, rs12934476, rs12457255, rs2297437, rs41309367, rs10733509, rs10750376, rs10932456, rs1326860, rs1528663, rs951279, rs9806914, rs7935393, rs1690492, rs420726, rs7759385, rs10974900, rs1326860, rs2548147, rs2815844, rs889702, rs9806914, rs7278257, or rs11221332, or an R of at least 0.85. 2It includes a fourth polymorphism that is in linkage disequilibrium with these and their combinations, or a proxy polymorphism that is in linkage disequilibrium with these. In some embodiments, at least three polymorphisms include rs6478109, rs56124762, and rs1892231. In some embodiments, at least three polymorphisms include rs6478109, rs56124762, and rs16901748. In some embodiments, at least three polymorphisms include rs6478109, rs1892231, and rs16901748. In some embodiments, at least three polymorphisms include rs6478109, rs1892231, and rs16901748. In some embodiments, the proxy polymorphisms in linkage disequilibrium are independently associated with a clinical phenotype associated with an inflammatory, fibrotic, or fibrostrictive disease or disorder of interest. In some embodiments, the clinical phenotype is a stricturing and penetrating disease.

[0019] In some embodiments, the presence of at least three polymorphisms predicts that the subject will therapeutically respond to an inhibitor of TL1A with at least about 70% positive median rate. In some embodiments, the presence of at least three polymorphisms predicts that the subject will therapeutically respond to an inhibitor of TL1A with at least about 75% positive median rate. In some embodiments, the presence of at least three polymorphisms predicts that the subject will therapeutically respond to an inhibitor of TL1A with at least about 80% positive median rate. In some embodiments, the presence of at least three polymorphisms predicts that the subject will therapeutically respond to an inhibitor of TL1A with at least about 85% positive median rate. In some embodiments, the presence of at least three polymorphisms predicts that the subject will therapeutically respond to an inhibitor of TL1A with at least about 90% positive median rate. In some embodiments, the presence of at least three polymorphisms predicts that the subject will therapeutically respond to an inhibitor of TL1A with at least about 95% positive median rate.

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

[0021] In some embodiments, at least three polymorphisms are detected in a sample by exposing the sample to an assay configured to detect the 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 includes polymerase chain reaction (PCR), quantitative reverse transcription PCR (qPCR), automated sequencing, or a genotyping array.

[0022] In some embodiments, the inflammatory, fibrotic, or fibrosing disorder or disease includes inflammatory bowel disease, Crohn's disease, obstructive Crohn's disease, ulcerative colitis, intestinal fibrosis, intestinal fibrotic stricture, rheumatoid arthritis, or primary sclerosing cholangitis. In some embodiments, Crohn's disease is ileal, ileocolonic, or colonic Crohn's disease. In some embodiments, the subject exhibits non-responsiveness or loss of response to, or is at risk of progressing this, to standard therapeutics including glucocorticosteroids, anti-TNF therapeutics, anti-a4-b7 therapeutics, anti-IL12p40 therapeutics, or combinations 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 human TL1A in the same region as a reference antibody selected from Table 2. In some embodiments, the method further includes administering an additional therapeutic agent to the subject.

[0023] Aspects disclosed herein provide a method for treating an inflammatory, fibrotic, or fibrostrictive disorder or disease of interest, the method comprising: (a) determining whether a subject having an inflammatory, fibrotic, or fibrostrictive disorder or disease is suitable for treatment with an inhibitor of TL1A activity or expression, the determining being performed by: (i) obtaining or having obtained a sample from the subject, and (ii) subjecting the sample to an assay suitable for detecting at least three polymorphisms predictive of the subject showing a therapeutic response to an inhibitor of TL1A activity or expression with at least about 70% positive median response; and (b) treating the subject by administering to the subject a therapeutically effective amount of an inhibitor of TL1A activity or expression, provided that at least three polymorphisms are detected. In some embodiments, the at least three polymorphisms are rs1892231, rs56124762, rs6478109, rs2070558, rs2070561, rs11897732, rs6740739, rs17796285, rs7935393, rs12934476, rs12457255, rs2070557, rs4246905, rs10974900, rs12434976, rs16901748, rs2815844, rs889702, rs2409750, rs1541020, rs4942248, rs12934476, rs12457255, rs2297437, rs41309367, rs10733509, rs10750376, rs10932456, rs1326860, rs1528663, rs951279, rs9806914, rs7935393, rs1690492, rs420726, rs7759385, rs10974900, rs1326860, rs2548147, rs2815844, rs889702, rs9806914, rs7278257, rs11221332, or proxy polymorphisms in linkage disequilibrium with these and / or combinations thereof as determined by 2 2 including, or combinations thereof.

[0024] In some embodiments, at least three polymorphic forms are rs6478109, rs56124762, and rs1892231, rs6478109, rs56124762, and rs16901748, rs6478109, rs1892231, and rs16901748, rs56124762, rs1892231, and rs16901748, rs6478109, rs2070558, and rs1892231, rs6478109, rs2070558, and rs16901748, rs6478109, rs1892231, and rs16901748, rs2070558, rs1892231, and rs16901748, rs6478109, rs2070561, and rs1892231, rs6478109, rs2070561, and rs16901748, rs6478109, rs1892231, and rs16901748, rs2070561, rs1892231, and rs16901748, rs6478109, rs7935393, and rs1892231, rs6478109, rs7935393, and rs9806914, rs6478109, rs7935393, and rs7278257, rs6478109, rs7935393, and rs2070557, rs6478109, rs1892231, and rs9806914, rs6478109, rs1892231, and rs7278257, rs6478109, rs1892231, and rs2070557, rs6478109, rs9806914, and rs7278257, rs6478109, rs9806914, and rs2070557, rs6478109, rs7278257, and rs2070557, rs7935393, rs1892231, and rs9806914, rs7935393, rs1892231, and rs7278257, rs7935393, rs1892231, and rs2070557, rs7935393, rs9806914, and rs7278257, rs7935393, rs9806914, and rs2070557, rs7935393, rs7278257, and rs2070557, rs1892231, rs9806914, and rs7278257,It includes rs1892231, rs9806914, and rs2070557, rs1892231, rs7278257, and rs2070557, or rs9806914, rs7278257, and rs2070557. In some embodiments, at least three polymorphisms further include rs16901748, rs1892231, rs56124762, rs6478109, rs2070558, rs2070561, rs11897732, rs6740739, rs17796285, rs7935393, rs12934476, rs12457255, rs2070557, rs4246905, rs10974900, rs12434976, rs2815844, rs889702, rs2409750, rs1541020, rs4942248, rs12934476, rs12457255, rs2297437, rs41309367, rs10733509, rs10750376, rs10932456, rs1326860, rs1528663, rs951279, rs9806914, rs7935393, rs1690492, rs420726, rs7759385, rs10974900, rs1326860, rs2548147, rs2815844, rs889702, rs9806914, rs7278257, or rs11221332, or an R of at least 0.85. 2 It includes a fourth polymorphism that includes proxy polymorphisms in linkage disequilibrium with these, or combinations thereof, as determined by 2 . In some embodiments, at least three polymorphisms include rs6478109, rs56124762, and rs1892231. In some embodiments, at least three polymorphisms include rs6478109, rs56124762, and rs16901748. In some embodiments, at least three polymorphisms include rs6478109, rs1892231, and rs16901748. In some embodiments, at least three polymorphisms include rs6478109, rs1892231, and rs16901748.

[0025] In some embodiments, at least three polymorphs are predicted to have a subject therapeutically respond to an inhibitor of TL1A with at least about 70% positive medium rate. In some embodiments, at least three polymorphs are predicted to have a subject therapeutically respond to an inhibitor of TL1A with at least about 75% positive medium rate. In some embodiments, at least three polymorphs are predicted to have a subject therapeutically respond to an inhibitor of TL1A with at least about 80% positive medium rate. In some embodiments, at least three polymorphs are predicted to have a subject therapeutically respond to an inhibitor of TL1A with at least about 85% positive medium rate. In some embodiments, at least three polymorphs are predicted to have a subject therapeutically respond to an inhibitor of TL1A with at least about 90% positive medium rate. In some embodiments, at least three polymorphs are predicted to have a subject therapeutically respond to an inhibitor of TL1A with at least about 95% positive medium rate.

[0026] In some embodiments, at least three polymorphs are predicted to have a subject therapeutically respond to an inhibitor of TL1A with at least about 70% specificity. In some embodiments, at least three polymorphs are predicted to have a subject therapeutically respond to an inhibitor of TL1A with at least about 75% specificity. In some embodiments, at least three polymorphs are predicted to have a subject therapeutically respond to an inhibitor of TL1A with at least about 80% specificity. In some embodiments, at least three polymorphs are predicted to have a subject therapeutically respond to an inhibitor of TL1A with at least about 85% specificity. In some embodiments, at least three polymorphs are predicted to have a subject therapeutically respond to an inhibitor of TL1A with at least about 90% specificity. In some embodiments, at least three polymorphs are predicted to have a subject therapeutically respond to an inhibitor of TL1A with at least about 95% specificity.

[0027] In some embodiments, the inflammatory, fibrotic, or fibrosing disorder or disease includes inflammatory bowel disease, Crohn's disease, obstructive Crohn's disease, ulcerative colitis, intestinal fibrosis, intestinal fibrosing stricture, rheumatoid arthritis, or primary sclerosing cholangitis. In some embodiments, Crohn's disease is Crohn's disease of the ileum, ileocolon, or colon. 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 human TL1A in the same region as the reference antibody selected from Table 2. In some embodiments, the method further includes administering an additional therapeutic agent to the subject.

[0028] In some embodiments, the subject is at risk of developing non-response or loss of response to standard therapeutic agents including glucocorticosteroids, anti-TNF therapeutic agents, anti-α4-β7 therapeutic agents, anti-IL12p40 therapeutic agents, or combinations thereof. In some embodiments, the proxy polymorphisms in linkage disequilibrium are independently associated with a clinical phenotype associated with the subject's inflammatory, fibrotic, or fibrosing disorder or disease. In some embodiments, the clinical phenotype is a stricturing and penetrating disease.

[0029] Aspects disclosed herein provide a method of treating an inflammatory, fibrotic, or fibrostrictive disorder or disease of interest, the method comprising: (a) determining whether a subject having an inflammatory, fibrotic, or fibrostrictive disorder or disease is suitable for treatment with an inhibitor of TL1A activity or expression, the determining being performed by: (i) obtaining or having obtained a sample from the subject, and (ii) subjecting the sample to an assay to detect at least three polymorphisms, including a proxy polymorphism in linkage disequilibrium with these when determined by 2 2 or a combination thereof; and (b) treating the subject by administering to the subject a therapeutically effective amount of an inhibitor of TL1A activity or expression.

[0030] In some embodiments, at least three polymorphic forms are rs6478109, rs56124762, and rs1892231, rs6478109, rs56124762, and rs16901748, rs6478109, rs1892231, and rs16901748, rs56124762, rs1892231, and rs16901748, rs6478109, rs2070558, and rs1892231, rs6478109, rs2070558, and rs16901748, rs6478109, rs1892231, and rs16901748, rs2070558, rs1892231, and rs16901748, rs6478109, rs2070561, and rs1892231, rs6478109, rs2070561, and rs16901748, rs6478109, rs1892231, and rs16901748, rs2070561, rs1892231, and rs16901748, rs6478109, rs7935393, and rs1892231, rs6478109, rs7935393, and rs9806914, rs6478109, rs7935393, and rs7278257, rs6478109, rs7935393, and rs2070557, rs6478109, rs1892231, and rs9806914, rs6478109, rs1892231, and rs7278257, rs6478109, rs1892231, and rs2070557, rs6478109, rs9806914, and rs7278257, rs6478109, rs9806914, and rs2070557, rs6478109, rs7278257, and rs2070557, rs7935393, rs1892231, and rs9806914, rs7935393, rs1892231, and rs7278257, rs7935393, rs1892231, and rs2070557, rs7935393, rs9806914, and rs7278257, rs7935393, rs9806914, and rs2070557, rs7935393, rs7278257, and rs2070557, rs1892231, rs9806914, and rs7278257,It includes rs1892231, rs9806914, and rs2070557, rs1892231, rs7278257, and rs2070557, or rs9806914, rs7278257, and rs2070557. In some embodiments, at least three polymorphisms further include rs16901748, rs1892231, rs56124762, rs6478109, rs2070558, rs2070561, rs11897732, rs6740739, rs17796285, rs7935393, rs12934476, rs12457255, rs2070557, rs4246905, rs10974900, rs12434976, rs2815844, rs889702, rs2409750, rs1541020, rs4942248, rs12934476, rs12457255, rs2297437, rs41309367, rs10733509, rs10750376, rs10932456, rs1326860, rs1528663, rs951279, rs9806914, rs7935393, rs1690492, rs420726, rs7759385, rs10974900, rs1326860, rs2548147, rs2815844, rs889702, rs9806914, rs7278257, or rs11221332, or at least 0.85 R, 2 It includes a fourth polymorphism that is in linkage disequilibrium with these and their combinations as determined by 2 , or proxy polymorphisms. In some embodiments, at least three polymorphisms include rs6478109, rs56124762, and rs1892231. In some embodiments, at least three polymorphisms include rs6478109, rs56124762, and rs16901748. In some embodiments, at least three polymorphisms include rs6478109, rs1892231, and rs16901748. In some embodiments, at least three polymorphisms include rs6478109, rs1892231, and rs16901748.

[0031] In some embodiments, at least three polymorphs predict that a subject will therapeutically respond to an inhibitor of TL1A with at least about 70% positive median rate. In some embodiments, at least three polymorphs predict that a subject will therapeutically respond to an inhibitor of TL1A with at least about 75% positive median rate. In some embodiments, at least three polymorphs predict that a subject will therapeutically respond to an inhibitor of TL1A with at least about 80% positive median rate. In some embodiments, at least three polymorphs predict that a subject will therapeutically respond to an inhibitor of TL1A with at least about 85% positive median rate. In some embodiments, at least three polymorphs predict that a subject will therapeutically respond to an inhibitor of TL1A with at least about 90% positive median rate. In some embodiments, at least three polymorphs predict that a subject will therapeutically respond to an inhibitor of TL1A with at least about 95% positive median rate.

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

[0033] In some embodiments, an inflammatory, fibrotic, or fibrosing disorder or disease includes inflammatory bowel disease, Crohn's disease, obstructive Crohn's disease, ulcerative colitis, intestinal fibrosis, intestinal fibrotic stricture, rheumatoid arthritis, or primary sclerosing cholangitis. In some embodiments, Crohn's disease is ileal, ileocolonic, or colonic Crohn's disease.

[0034] 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 human TL1A in the same region as the reference antibodies selected from Table 2. In some embodiments, the method further comprises administering an additional therapeutic agent to the subject.

[0035] In some embodiments, the subject is at risk of progressing to non-response or loss of response to standard-of-care agents including glucocorticoids, anti-TNF therapeutic agents, anti-α4-β7 therapeutic agents, anti-IL12p40 therapeutic agents, or combinations thereof. In some embodiments, proxy polymorphisms in linkage disequilibrium are independently associated with clinical phenotypes associated with the subject's inflammatory, fibrotic, or fibrostrictive disease or disorder. In some embodiments, the clinical phenotype is a stricturing and penetrating disease.

[0036] Aspects disclosed herein provide a method of treating an inflammatory, fibrotic, or fibrostrictive disease or disorder of a subject, the method comprising administering to the subject a therapeutically effective amount of an inhibitor of TL1A activity or expression, wherein the subject has rs16901748, rs6478109, rs56124762, or an R of at least 0.85 2Express at least three polymorphisms that are in linkage disequilibrium with these when determined by . In some embodiments, the at least three polymorphisms further include rs16901748, rs1892231, rs56124762, rs6478109, rs2070558, rs2070561, rs11897732, rs6740739, rs17796285, rs7935393, rs12934476, rs12457255, rs2070557, rs4246905, rs10974900, rs12434976, rs2815844, rs889702, rs2409750, rs1541020, rs4942248, rs12934476, rs12457255, rs2297437, rs41309367, rs10733509, rs10750376, rs10932456, rs1326860, rs1528663, rs951279, rs9806914, rs7935393, rs1690492, rs420726, rs7759385, rs10974900, rs1326860, rs2548147, rs2815844, rs889702, rs9806914, rs7278257, or rs11221332, or an R of at least 0.85 2It includes a fourth polymorphism that is in linkage disequilibrium with these when determined, or combinations thereof, of proxy polymorphisms. In some embodiments, at least three polymorphisms predict that a subject will therapeutically respond to an inhibitor of TL1A with a positive median rate of at least about 70%. In some embodiments, at least three polymorphisms predict that a subject will therapeutically respond to an inhibitor of TL1A with a positive median rate of at least about 75%. In some embodiments, at least three polymorphisms predict that a subject will therapeutically respond to an inhibitor of TL1A with a positive median rate of at least about 80%. In some embodiments, at least three polymorphisms predict that a subject will therapeutically respond to an inhibitor of TL1A with a positive median rate of at least about 85%. In some embodiments, at least three polymorphisms predict that a subject will therapeutically respond to an inhibitor of TL1A with a positive median rate of at least about 90%. In some embodiments, at least three polymorphisms predict that a subject will therapeutically respond to an inhibitor of TL1A with a positive median rate of at least about 95%. In some embodiments, at least three polymorphisms predict that a subject will therapeutically respond to an inhibitor of TL1A with a specificity of at least about 70%. In some embodiments, at least three polymorphisms predict that a subject will therapeutically respond to an inhibitor of TL1A with a specificity of at least about 75%. In some embodiments, at least three polymorphisms predict that a subject will therapeutically respond to an inhibitor of TL1A with a specificity of at least about 80%. In some embodiments, at least three polymorphisms predict that a subject will therapeutically respond to an inhibitor of TL1A with a specificity of at least about 85%. In some embodiments, at least three polymorphisms predict that a subject will therapeutically respond to an inhibitor of TL1A with a specificity of at least about 90%. In some embodiments, at least three polymorphisms predict that a subject will therapeutically respond to an inhibitor of TL1A with a specificity of at least about 95%. In some embodiments, the inflammatory, fibrotic, or fibrostrictive disease or disorder includes inflammatory bowel disease, Crohn's disease, obstructive Crohn's disease, ulcerative colitis, intestinal fibrosis, intestinal fibrostricture, rheumatoid arthritis, or primary sclerosing cholangitis. In some embodiments, 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 human TL1A in the same region as the reference antibodies selected from Table 2. In some embodiments, the method further comprises administering an additional therapeutic agent to the subject. In some embodiments, the subject is at risk of progressing non-response or loss of response to standard therapeutic agents including glucocorticoids, anti-TNF therapeutic agents, anti-α4-β7 therapeutic agents, anti-IL12p40 therapeutic agents, or combinations thereof. In some embodiments, the proxy polymorphisms in linkage disequilibrium are independently associated with clinical phenotypes associated with the inflammatory, fibrotic, or fibrostrictive disease or disorder of the subject. In some embodiments, the clinical phenotype is a stricturing and penetrating disease.

[0037] Aspects disclosed herein provide a method comprising: (a) providing a sample obtained from a subject having an inflammatory, fibrotic, or fibrostrictive disorder or disease; and (b) detecting the presence of at least three polymorphisms in the sample by a genotyping assay, wherein the presence of the at least three polymorphisms predicts the treatment response of the subject to treatment with an inhibitor of TL1A activity or expression with at least about 70% positive concordance. In some embodiments, the at least three polymorphisms are rs1892231, rs56124762, rs6478109, rs2070558, rs2070561, rs11897732, rs6740739, rs17796285, rs7935393, rs12934476, rs12457255, rs2070557, rs4246905, rs10974900, rs12434976, rs16901748, rs2815844, rs889702, rs2409750, rs1541020, rs4942248, rs12934476, rs12457255, rs2297437, rs41309367, rs10733509, rs10750376, rs10932456, rs1326860, rs1528663, rs951279, rs9806914, rs7935393, rs1690492, rs420726, rs7759385, rs10974900, rs1326860, rs2548147, rs2815844, rs889702, rs9806914, rs7278257, rs11221332, or proxy polymorphisms in linkage disequilibrium with these as determined by R 2

[0038] ​In some embodiments, the step of detecting at least three polymorphs comprises detecting at least three genotypes corresponding to nucleic acid position 501 within SEQ ID NOs: 1-41 or 57-59. In some embodiments, the presence of at least three polymorphs predicts that the subject will therapeutically respond to an inhibitor of TL1A with at least about 75% positive median rate. In some embodiments, the presence of at least three polymorphs predicts that the subject will therapeutically respond to an inhibitor of TL1A with at least about 80% positive median rate. In some embodiments, the presence of at least three polymorphs predicts that the subject will therapeutically respond to an inhibitor of TL1A with at least about 85% positive median rate. In some embodiments, the presence of at least three polymorphs predicts that the subject will therapeutically respond to an inhibitor of TL1A with at least about 90% positive median rate. In some embodiments, the presence of at least three polymorphs predicts that the subject will therapeutically respond to an inhibitor of TL1A with at least about 95% positive median rate.

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

[0040] In some embodiments, the method further comprises administering to the subject a therapeutically effective amount of an inhibitor of TL1A activity or expression to treat an inflammatory, fibrotic, or fibrosing disorder or disease. In some embodiments, the subject is at risk of developing non-response or loss of response to standard therapies including glucocorticoids, anti-TNF therapies, anti-a4-b7 therapies, anti-IL12p40 therapies, or combinations thereof. In some embodiments, the inflammatory, fibrotic, or fibrosing disorder or disease includes 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 inhibitor of TL1A activity or expression is an anti-TL1A antibody or antigen-binding fragment. In some embodiments, the anti-TL1A antibody binds to human TL1A in the same region as a reference antibody selected from Table 2. In some embodiments, the method further comprises administering an additional therapeutic agent to the subject.

[0042] In some embodiments, at least three polymorphic forms are rs6478109, rs56124762, and rs1892231, rs6478109, rs56124762, and rs16901748, rs6478109, rs1892231, and rs16901748, rs56124762, rs1892231, and rs16901748, rs6478109, rs2070558, and rs1892231, rs6478109, rs2070558, and rs16901748, rs6478109, rs1892231, and rs16901748, rs2070558, rs1892231, and rs16901748, rs6478109, rs2070561, and rs1892231, rs6478109, rs2070561, and rs16901748, rs6478109, rs1892231, and rs16901748, rs2070561, rs1892231, and rs16901748, rs6478109, rs7935393, and rs1892231, rs6478109, rs7935393, and rs9806914, rs6478109, rs7935393, and rs7278257, rs6478109, rs7935393, and rs2070557, rs6478109, rs1892231, and rs9806914, rs6478109, rs1892231, and rs7278257, rs6478109, rs1892231, and rs2070557, rs6478109, rs9806914, and rs7278257, rs6478109, rs9806914, and rs2070557, rs6478109, rs7278257, and rs2070557, rs7935393, rs1892231, and rs9806914, rs7935393, rs1892231, and rs7278257, rs7935393, rs1892231, and rs2070557, rs7935393, rs9806914, and rs7278257, rs7935393, rs9806914, and rs2070557, rs7935393, rs7278257, and rs2070557, rs1892231, rs9806914, and rs7278257,It includes rs1892231, rs9806914, and rs2070557, rs1892231, rs7278257, and rs2070557, or rs9806914, rs7278257, and rs2070557. In some embodiments, at least three polymorphisms further include rs16901748, rs1892231, rs56124762, rs6478109, rs2070558, rs2070561, rs11897732, rs6740739, rs17796285, rs7935393, rs12934476, rs12457255, rs2070557, rs4246905, rs10974900, rs12434976, rs2815844, rs889702, rs2409750, rs1541020, rs4942248, rs12934476, rs12457255, rs2297437, rs41309367, rs10733509, rs10750376, rs10932456, rs1326860, rs1528663, rs951279, rs9806914, rs7935393, rs1690492, rs420726, rs7759385, rs10974900, rs1326860, rs2548147, rs2815844, rs889702, rs9806914, rs7278257, or rs11221332, or combinations thereof, including a fourth polymorphism. In some embodiments, at least three polymorphisms include rs6478109, rs56124762, and rs1892231. In some embodiments, at least three polymorphisms include rs6478109, rs56124762, and rs16901748. In some embodiments, at least three polymorphisms include rs6478109, rs1892231, and rs16901748. In some embodiments, at least three polymorphisms include rs6478109, rs1892231, and rs16901748. In some embodiments, proxy polymorphisms in linkage disequilibrium are independently associated with a clinical phenotype associated with an inflammatory, fibrotic, or fibrostrictive disease or disorder of interest. In some embodiments, the clinical phenotype is a stricturing and penetrating disease.,

[0043] Aspects disclosed herein provide a method comprising: (a) providing a sample obtained from a subject with an inflammatory, fibrotic, or fibrostrictive disorder or disease; and (b) detecting the presence of at least three polymorphisms in the sample by a genotyping assay, wherein the at least three polymorphisms are rs1892231, rs56124762, rs6478109, rs2070558, rs2070561, rs11897732, rs6740739, rs17796285, rs7935393, rs12934476, rs12457255, rs2070557, rs4246905, rs10974900, rs12434976, rs16901748, rs2815844, rs889702, rs2409750, rs1541020, rs4942248, rs12934476, rs12457255, rs2297437, rs41309367, rs10733509, rs10750376, rs10932456, rs1326860, rs1528663, rs951279, rs9806914, rs7935393, rs1690492, rs420726, rs7759385, rs10974900, rs1326860, rs2548147, rs2815844, rs889702, rs9806914, rs7278257, rs11221332, or proxy polymorphisms in linkage disequilibrium with these, or combinations thereof, as determined by an R 2 of at least 0.85 when so determined.

[0044] In some embodiments, the step of detecting at least three polymorphs comprises detecting at least three genotypes corresponding to nucleic acid position 501 within SEQ ID NOs: 1-41 or 57-59. In some embodiments, the presence of at least three polymorphs predicts the treatment response of a subject to treatment with an inhibitor of TL1A with a positive medium rate of at least about 70%. In some embodiments, the presence of at least three polymorphs predicts the treatment response of a subject to treatment with an inhibitor of TL1A with a positive medium rate of at least about 75%. In some embodiments, the presence of at least three polymorphs predicts the treatment response of a subject to treatment with an inhibitor of TL1A with a positive medium rate of at least about 80%. In some embodiments, the presence of at least three polymorphs predicts the treatment response of a subject to treatment with an inhibitor of TL1A with a positive medium rate of at least about 85%. In some embodiments, the presence of at least three polymorphs predicts the treatment response of a subject to treatment with an inhibitor of TL1A with a positive medium rate of at least about 90%. In some embodiments, the presence of at least three polymorphs predicts the treatment response of a subject to treatment with an inhibitor of TL1A with a positive medium rate of at least about 95%.

[0045] In some embodiments, the presence of at least three polymorphs predicts the treatment response of a subject to treatment with an inhibitor of TL1A with a specificity of at least about 70%. In some embodiments, the presence of at least three polymorphs predicts the treatment response of a subject to treatment with an inhibitor of TL1A with a specificity of at least about 75%. In some embodiments, the presence of at least three polymorphs predicts the treatment response of a subject to treatment with an inhibitor of TL1A with a specificity of at least about 80%. In some embodiments, the presence of at least three polymorphs predicts the treatment response of a subject to treatment with an inhibitor of TL1A with a specificity of at least about 85%. In some embodiments, the presence of at least three polymorphs predicts the treatment response of a subject to treatment with an inhibitor of TL1A with a specificity of at least about 90%. In some embodiments, the presence of at least three polymorphs predicts the treatment response of a subject to treatment with an inhibitor of TL1A with a specificity of at least about 95%.

[0046] In some embodiments, the method further comprises administering to the subject a therapeutically effective amount of an inhibitor of TL1A activity or expression to treat an inflammatory, fibrotic, or fibrostrictive disorder or disease. In some embodiments, the subject is at risk of progressing to non-responsiveness or loss of response to standard therapeutics including glucocorticosteroids, anti-TNF therapeutics, anti-a4-b7 therapeutics, anti-IL12p40 therapeutics, or combinations thereof. In some embodiments, the inflammatory, fibrotic, or fibrostrictive disorder or disease includes 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 inhibitor of TL1A activity or expression is an anti-TL1A antibody or antigen-binding fragment. In some embodiments, the anti-TL1A antibody binds to human TL1A in the same region as a reference antibody selected from Table 2. In some embodiments, the method further comprises administering an additional therapeutic to the subject.

[0048] In some embodiments, at least three polymorphic forms are rs6478109, rs56124762, and rs1892231, rs6478109, rs56124762, and rs16901748, rs6478109, rs1892231, and rs16901748, rs56124762, rs1892231, and rs16901748, rs6478109, rs2070558, and rs1892231, rs6478109, rs2070558, and rs16901748, rs6478109, rs1892231, and rs16901748, rs2070558, rs1892231, and rs16901748, rs6478109, rs2070561, and rs1892231, rs6478109, rs2070561, and rs16901748, rs6478109, rs1892231, and rs16901748, rs2070561, rs1892231, and rs16901748, rs6478109, rs7935393, and rs1892231, rs6478109, rs7935393, and rs9806914, rs6478109, rs7935393, and rs7278257, rs6478109, rs7935393, and rs2070557, rs6478109, rs1892231, and rs9806914, rs6478109, rs1892231, and rs7278257, rs6478109, rs1892231, and rs2070557, rs6478109, rs9806914, and rs7278257, rs6478109, rs9806914, and rs2070557, rs6478109, rs7278257, and rs2070557, rs7935393, rs1892231, and rs9806914, rs7935393, rs1892231, and rs7278257, rs7935393, rs1892231, and rs2070557, rs7935393, rs9806914, and rs7278257, rs7935393, rs9806914, and rs2070557, rs7935393, rs7278257, and rs2070557, rs1892231, rs9806914, and rs7278257,It includes rs1892231, rs9806914, and rs2070557, rs1892231, rs7278257, and rs2070557, or rs9806914, rs7278257, and rs2070557. In some embodiments, at least three polymorphisms further include rs16901748, rs1892231, rs56124762, rs6478109, rs2070558, rs2070561, rs11897732, rs6740739, rs17796285, rs7935393, rs12934476, rs12457255, rs2070557, rs4246905, rs10974900, rs12434976, rs2815844, rs889702, rs2409750, rs1541020, rs4942248, rs12934476, rs12457255, rs2297437, rs41309367, rs10733509, rs10750376, rs10932456, rs1326860, rs1528663, rs951279, rs9806914, rs7935393, rs1690492, rs420726, rs7759385, rs10974900, rs1326860, rs2548147, rs2815844, rs889702, rs9806914, rs7278257, or rs11221332, or combinations thereof, including a fourth polymorphism. In some embodiments, at least three polymorphisms include rs6478109, rs56124762, and rs1892231. In some embodiments, at least three polymorphisms include rs6478109, rs56124762, and rs16901748. In some embodiments, at least three polymorphisms include rs6478109, rs1892231, and rs16901748. In some embodiments, at least three polymorphisms include rs6478109, rs1892231, and rs16901748. In some embodiments, proxy polymorphisms in linkage disequilibrium are independently associated with clinical phenotypes associated with the inflammatory, fibrotic, or fibrostrictive disease or disorder of interest. In some embodiments, the clinical phenotype is a stricturing and penetrating disease.,

[0049] Aspects disclosed herein include: (a) receiving genotype data of a subject with an inflammatory, fibrotic, or fibrosing stenotic disorder or disease; and (b) analyzing the genotype to detect the presence of at least three genotypes that predict the subject's treatment response to treatment with an inhibitor of tumor necrosis factor-like cytokine 1A (TL1A) activity or expression for treating an inflammatory, fibrotic, or fibrosing stenotic disorder or disease with a positive median rate of at least about 70%. In some embodiments, the at least three genotypes are rs1892231, rs56124762, rs6478109, rs2070558, rs2070561, rs11897732, rs6740739, rs17796285, rs7935393, rs12934476, rs12457255, rs2070557, rs4246905, rs10974900, rs12434976, rs16901748, rs2815844, rs889702, rs2409750, rs1541020, rs4942248, rs12934476, rs12457255, rs2297437, rs41309367, rs10733509, rs10750376, rs10932456, rs1326860, rs1528663, rs951279, rs9806914, rs7935393, rs1690492, rs420726, rs7759385, rs10974900, rs1326860, rs2548147, rs2815844, rs889702, rs9806914, rs7278257, or rs11221332, or at least 0.85 R 2 including at least three polymorphisms including proxy polymorphisms in linkage disequilibrium with these or combinations thereof as determined by R

[0050] In some embodiments, the method further includes generating a TNFSF15 profile including positive, negative, or indeterminate results regarding treatment response treatment with an inhibitor of TL1A activity or expression.

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

[0052] In some embodiments, the determination of whether a subject is likely to respond therapeutically to treatment with an inhibitor of TL1A activity or expression is performed with a specificity of at least about 70%. In some embodiments, the determination of whether a subject is likely to respond therapeutically to treatment with an inhibitor of TL1A activity or expression is performed with a specificity of at least about 75%. In some embodiments, the determination of whether a subject is likely to respond therapeutically to treatment with an inhibitor of TL1A activity or expression is performed with a specificity of at least about 80%. In some embodiments, the determination of whether a subject is likely to respond therapeutically to treatment with an inhibitor of TL1A activity or expression is performed with a specificity of at least about 85%. In some embodiments, the determination of whether a subject is likely to respond therapeutically to treatment with an inhibitor of TL1A activity or expression is performed with a specificity of at least about 90%. In some embodiments, the determination of whether a subject is likely to respond therapeutically to treatment with an inhibitor of TL1A activity or expression is performed with a specificity of at least about 95%.

[0053] In some embodiments, at least three polymorphic forms are rs6478109, rs56124762, and rs1892231, rs6478109, rs56124762, and rs16901748, rs6478109, rs1892231, and rs16901748, rs56124762, rs1892231, and rs16901748, rs6478109, rs2070558, and rs1892231, rs6478109, rs2070558, and rs16901748, rs6478109, rs1892231, and rs16901748, rs2070558, rs1892231, and rs16901748, rs6478109, rs2070561, and rs1892231, rs6478109, rs2070561, and rs16901748, rs6478109, rs1892231, and rs16901748, rs2070561, rs1892231, and rs16901748, rs6478109, rs7935393, and rs1892231, rs6478109, rs7935393, and rs9806914, rs6478109, rs7935393, and rs7278257, rs6478109, rs7935393, and rs2070557, rs6478109, rs1892231, and rs9806914, rs6478109, rs1892231, and rs7278257, rs6478109, rs1892231, and rs2070557, rs6478109, rs9806914, and rs7278257, rs6478109, rs9806914, and rs2070557, rs6478109, rs7278257, and rs2070557, rs7935393, rs1892231, and rs9806914, rs7935393, rs1892231, and rs7278257, rs7935393, rs1892231, and rs2070557, rs7935393, rs9806914, and rs7278257, rs7935393, rs9806914, and rs2070557, rs7935393, rs7278257, and rs2070557, rs1892231, rs9806914, and rs7278257,It includes rs1892231, rs9806914, and rs2070557, rs1892231, rs7278257, and rs2070557, or rs9806914, rs7278257, and rs2070557. In some embodiments, at least three polymorphisms further include rs16901748, rs1892231, rs56124762, rs6478109, rs2070558, rs2070561, rs11897732, rs6740739, rs17796285, rs7935393, rs12934476, rs12457255, rs2070557, rs4246905, rs10974900, rs12434976, rs2815844, rs889702, rs2409750, rs1541020, rs4942248, rs12934476, rs12457255, rs2297437, rs41309367, rs10733509, rs10750376, rs10932456, rs1326860, rs1528663, rs951279, rs9806914, rs7935393, rs1690492, rs420726, rs7759385, rs10974900, rs1326860, rs2548147, rs2815844, rs889702, rs9806914, rs7278257, or rs11221332, or at least 0.85 R, 2 It includes a fourth polymorphism that is in linkage disequilibrium with these and proxy polymorphisms determined by 2 , or combinations thereof. In some embodiments, at least three polymorphisms include rs6478109, rs56124762, and rs1892231. In some embodiments, at least three polymorphisms include rs6478109, rs56124762, and rs16901748. In some embodiments, at least three polymorphisms include rs6478109, rs1892231, and rs16901748. In some embodiments, at least three polymorphisms include rs6478109, rs1892231, and rs16901748.

[0054] In some embodiments, the method further includes creating a report that includes a TNFSF15 profile for display to a user. In some embodiments, the inflammatory, fibrotic, or fibrostrictive disorder or disease includes 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, 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 human TL1A in the same region as a reference antibody selected from Table 2. In some embodiments, the proxy polymorphisms in linkage disequilibrium are independently associated with a clinical phenotype associated with the inflammatory, fibrotic, or fibrostrictive disorder or disease of the subject. In some embodiments, the clinical phenotype is a stricturing and penetrating disease.

[0055] Aspects disclosed herein provide a kit comprising: (a) at least three primer pairs, each comprising a first primer and a second primer, wherein the first primer comprises at least 10 contiguous nucleic acids corresponding to nucleotides 4090-500 of SEQ ID NOs: 1-41 or 57-59, and the second primer comprises at least 10 contiguous nucleic acids corresponding to nucleotides 4090-500 of the reverse complement of SEQ ID NOs: 1-41 or 57-59; and (b) at least three polynucleotide molecules, each comprising a detectable moiety and comprising a nucleic acid sequence comprising a nucleotide corresponding to nucleic acid 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, fibrotic, or fibrostrictive disorder or disease for treatment with an inhibitor of TL1A activity or expression, provided that the presence of at least three polymorphisms is detected in a sample obtained from the patient.

[0056] Aspects disclosed herein provide a kit comprising: (a) a first primer pair comprising a first forward primer provided in any one of SEQ ID NOs: 364101 to 364110 and a corresponding first reverse primer provided in any one of SEQ ID NOs: 364111 to 364120; (b) a second primer pair comprising a second forward primer provided in any one of SEQ ID NOs: 364101 to 364110 and a corresponding second reverse primer provided in any one of SEQ ID NOs: 364111 to 364120; (c) a third primer pair comprising a third forward primer provided in any one of SEQ ID NOs: 364101 to 364110 and a corresponding third reverse primer provided in any one of SEQ ID NOs: 364111 to 364120; and (d) at least three polynucleotide molecules each comprising a detectable moiety and comprising a nucleic acid sequence comprising a nucleotide corresponding to nucleic acid position 501 of SEQ ID NOs: 1 to 41 or 57 to 59, wherein the first primer pair, the second primer pair, and the third primer pair are not the same. In some embodiments, this kit is useful for selecting patients with inflammatory, fibrotic, or fibrostrictive diseases or disorders for treatment with an inhibitor of TL1A activity or expression, provided that the presence of at least three polymorphisms is detected in a sample obtained from the patient.

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

[0058] Aspects of the disclosure provide a non-transitory computer-readable medium including machine-executable code that, when executed by one or more computer processors, performs any of the methods described above or elsewhere in this specification.

[0059] Aspects of the disclosure provide a system including one or more computer processors and a computer memory coupled to the processors. The computer memory includes machine-executable code that, when executed by one or more computer processors, performs any of the methods described above or elsewhere in this specification.

[0060] Aspects provided herein provide a method of treating at least one of an inflammatory, fibrotic, or fibrostrictive disorder or disease of interest, the method comprising administering to the subject a therapeutically effective amount of an inhibitor of TL1A activity or expression, provided that the 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 are selected from the group consisting of rs11897732, rs6740739, rs17796285, rs7935393, rs12934476, rs12457255, rs2070557, rs4246905, rs10974900, rs12434976, rs16901748, rs2815844, rs889702, rs2409750, rs1541020, rs4942248, rs12934476, rs12457255, rs2297437, rs41309367, rs10733509, rs10750376, rs10932456, rs1326860, rs1528663, rs1892231, rs951279, rs9806914, rs7935393, rs1690492, rs420726, rs7759385, rs10974900, rs1326860, rs2548147, rs2815844, rs889702, rs9806914, rs6478109, rs7278257, and rs11221332.In some embodiments, at least three polymorphisms are selected from the group consisting of the "G" allele at rs11897732, the "A" allele at rs6740739, the "G" allele at rs17796285, the "A" allele at rs7935393, the "G" allele at rs12934476, the "A" allele at rs12457255, the "A" allele at rs2070557, the "A" allele at rs4246905, the "A" allele at rs10974900, the "C" allele at rs12434976, the "A" allele at rs16901748, the "A" allele at rs2815844, the "G" allele at rs889702, the "C" allele at rs2409750, the "A" allele at rs1541020, the "T" allele at rs4942248, the "G" allele at rs12934476, the "A" allele at rs12457255, the "A" allele at rs2297437, the "G" allele at rs41309367, the "A" allele at rs10733509, the "G" allele at rs10750376, the "G" allele at rs10932456, the "A" allele at rs1326860, the "G" allele at rs1528663, the "C" allele at rs1892231, the "A" allele at rs951279, the "A" allele at rs9806914, the "A" allele at rs7935393, the "G" allele at rs1690492, the "A" allele at rs420726, the "T" allele at rs7759385, the "A" allele at rs10974900, the "A" allele at rs1326860, the "C" allele at rs2548147, the "A" allele at rs2815844, the "G" allele at rs889702, the "A" allele at rs9806914, the "A" allele at rs6478109, the "C" allele at rs7278257, and the "A" allele at rs11221332. In some embodiments, one of the at least three polymorphisms comprises the minor allele provided in Table 1. In some embodiments, one of the at least three polymorphisms comprises the major allele provided in Table 1. In some embodiments, the genotype is heterozygous.In some embodiments, the genotype is homozygous. In some embodiments, at least three polymorphisms include imm_9_116608587, imm_11_127948309, and rs1892231. In some embodiments, at least three polymorphisms include imm_9_116608587, imm_11_127948309, and rs9806914. In some embodiments, at least three polymorphisms include imm_9_116608587, imm_11_127948309, and imm_21_44478192. In some embodiments, at least three polymorphisms include imm_9_116608587, imm_11_127948309, and imm_21_44479552. In some embodiments, at least three polymorphisms include imm_9_116608587, rs1892231, and rs9806914. In some embodiments, at least three polymorphisms include imm_9_116608587, rs1892231, and imm_21_44478192. In some embodiments, at least three polymorphisms include imm_9_116608587, rs1892231, and imm_21_44479552. In some embodiments, at least three polymorphisms include imm_9_116608587, rs9806914, and imm_21_44478192. In some embodiments, at least three polymorphisms include imm_9_116608587, rs9806914, and imm_21_44478192. In some embodiments, at least three polymorphisms include imm_9_116608587, imm_21_44478192, and imm_21_44479552. In some embodiments, at least three polymorphisms include imm_11_127948309, rs1892231, and rs9806914. In some embodiments, at least three polymorphisms include imm_11_127948309, rs1892231, and imm_21_44478192. In some embodiments, at least three polymorphisms include imm_11_127948309, rs1892231, and imm_21_44479552.In some embodiments, at least three polymorphs include imm_11_127948309, rsrs9806914, and imm_21_44478192. In some embodiments, at least three polymorphs include imm_11_127948309, rsrs9806914, and imm_21_44479552. In some embodiments, at least three polymorphs include imm_11_127948309, imm_21_44478192, and imm_21_44479552. In some embodiments, at least three polymorphs include rs1892231, rs9806914, and imm_21_44478192. In some embodiments, at least three polymorphs include rs1892231, rs9806914, and imm_21_44478192. In some embodiments, at least three polymorphs include rs1892231, imm_21_44478192, and imm_21_44479552. In some embodiments, at least three polymorphs include rs9806914, imm_21_44478192, and imm_21_44479552. In some embodiments, at least three polymorphs are detected in a sample obtained from a subject by: (a) a process of subjecting a 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, wherein the at least 10 contiguous nucleic acid molecules include a risk allele at nucleotide position 251 or 501 within SEQ ID NOs: 1-41 or 57-59; and (b) a process of detecting at least 10 contiguous nucleic acid molecules in 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, genotyping arrays, or combinations thereof. In some embodiments, the inflammatory disease or disorder is selected from the group consisting of inflammatory bowel disease (IBD), Crohn's disease (CD), obstructive CD, ulcerative colitis (UC), intestinal fibrosis, intestinal fibrotic stricture, and primary sclerosing cholangitis. In some embodiments, the CD is ileal, ileocolonic, or colonic CD.In some embodiments, the subject is non-responsive or has lost responsiveness to, or is at risk of progressing to, standard of care agents, which are selected from the group consisting of glucocorticosteroids, anti-TNF therapeutic agents, anti-a4-b7 therapeutic agents (vedolizumab), anti-IL12p40 therapeutic agents (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 human TL1A in the same region as a reference antibody selected from Table 2. In some embodiments, the anti-TL1A antibody is a neutralizing TL1A antibody or antigen-binding fragment.

[0061] Aspects disclosed herein provide a method of selecting a subject for treatment with an inhibitor of TL1A activity or expression, the method comprising: (a) contacting a sample containing genetic material obtained from the subject with an assay suitable for detecting the presence of a 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 on the premise that the presence of the genotype is detected in (a). In some embodiments, the method further comprises administering or prescribing to the subject an inhibitor of TL1A activity or expression in a therapeutically effective amount. In some embodiments, the method further comprises determining whether the subject is at risk of non-response or loss of response progression to a standard therapeutic agent, the standard therapeutic agent being selected from the group consisting of glucocorticoids, anti-TNF therapeutic agents, anti-a4-b7 therapeutic agents (vedolizumab), anti-IL12p40 therapeutic agents (ustekinumab), thalidomide, and cytokines. 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 human TL1A in the same region as a reference antibody selected from Table 2. In some embodiments, the anti-TL1A antibody is a neutralizing anti-TL1A antibody or antigen-binding fragment.In some embodiments, at least three polymorphisms are selected from the group consisting of rs11897732, rs6740739, rs17796285, rs7935393, rs12934476, rs12457255, rs2070557, rs4246905, rs10974900, rs12434976, rs16901748, rs2815844, rs889702, rs2409750, rs1541020, rs4942248, rs12934476, rs12457255, rs2297437, rs41309367, rs10733509, rs10750376, rs10932456, rs1326860, rs1528663, rs1892231, rs951279, rs9806914, rs7935393, rs1690492, rs420726, rs7759385, rs10974900, rs1326860, rs2548147, rs2815844, rs889702, rs9806914, rs6478109, rs7278257, and rs11221332. In some embodiments, one of the at least three polymorphisms comprises the minor allele provided in Table 1. In some embodiments, one of the at least three polymorphisms comprises the major allele provided in Table 1. In some embodiments, the genotype is heterozygous. In some embodiments, the genotype is homozygous.In some embodiments, at least three polymorphisms are selected from the group consisting of the "G" allele at rs11897732, the "A" allele at rs6740739, the "G" allele at rs17796285, the "A" allele at rs7935393, the "G" allele at rs12934476, the "A" allele at rs12457255, the "A" allele at rs2070557, the "A" allele at rs4246905, the "A" allele at rs10974900, the "C" allele at rs12434976, the "A" allele at rs16901748, the "A" allele at rs2815844, the "G" allele at rs889702, the "C" allele at rs2409750, the "A" allele at rs1541020, the "T" allele at rs4942248, the "G" allele at rs12934476, the "A" allele at rs12457255, the "A" allele at rs2297437, the "G" allele at rs41309367, the "A" allele at rs10733509, the "G" allele at rs10750376, the "G" allele at rs10932456, the "A" allele at rs1326860, the "G" allele at rs1528663, the "C" allele at rs1892231, the "A" allele at rs951279, the "A" allele at rs9806914, the "A" allele at rs7935393, the "G" allele at rs1690492, the "A" allele at rs420726, the "T" allele at rs7759385, the "A" allele at rs10974900, the "A" allele at rs1326860, the "C" allele at rs2548147, the "A" allele at rs2815844, the "G" allele at rs889702, the "A" allele at rs9806914, the "A" allele at rs6478109, the "C" allele at rs7278257, and the "A" allele at rs11221332. In some embodiments, at least three polymorphisms include imm_9_116608587, imm_11_127948309, and rs1892231.In some embodiments, at least three polymorphisms include imm_9_116608587, imm_11_127948309, and rs9806914. In some embodiments, at least three polymorphisms include imm_9_116608587, imm_11_127948309, and imm_21_44478192. In some embodiments, at least three polymorphisms include imm_9_116608587, imm_11_127948309, and imm_21_44479552. In some embodiments, at least three polymorphisms include imm_9_116608587, rs1892231, and rs9806914. In some embodiments, at least three polymorphisms include imm_9_116608587, rs1892231, and imm_21_44478192. In some embodiments, at least three polymorphisms include imm_9_116608587, rs1892231, and imm_21_44479552. In some embodiments, at least three polymorphisms include imm_9_116608587, rs9806914, and imm_21_44478192. In some embodiments, at least three polymorphisms include imm_9_116608587, rs9806914, and imm_21_44478192. In some embodiments, at least three polymorphisms include imm_9_116608587, imm_21_44478192, and imm_21_44479552. In some embodiments, at least three polymorphisms include imm_11_127948309, rs1892231, and rs9806914. In some embodiments, at least three polymorphisms include imm_11_127948309, rs1892231, and imm_21_44478192. In some embodiments, at least three polymorphisms include imm_11_127948309, rs1892231, and imm_21_44479552. In some embodiments, at least three polymorphisms include imm_11_127948309, rsrs9806914, and imm_21_44478192.In some embodiments, at least three polymorphisms include imm_11_127948309, rsrs9806914, and imm_21_44479552. In some embodiments, at least three polymorphisms include imm_11_127948309, imm_21_44478192, and imm_21_44479552. In some embodiments, at least three polymorphisms include rs1892231, rs9806914, and imm_21_44478192. In some embodiments, at least three polymorphisms include rs1892231, rs9806914, and imm_21_44478192. In some embodiments, at least three polymorphisms include rs1892231, imm_21_44478192, and imm_21_44479552. In some embodiments, at least three polymorphisms include rs9806914, imm_21_44478192, and imm_21_44479552.

[0062] Aspects disclosed herein provide a method of treating at least one of an inflammatory, fibrotic, and fibrostrictive disorder or disease of interest, the method comprising: (a) determining whether the subject is at risk of non - responding or losing response to a standard therapeutic agent; and (b) determining whether the subject is suitable for treatment with an inhibitor of TL1A activity or expression, the determination being made by: (i) contacting a sample obtained from the subject with an assay suitable for detecting the presence of a genotype comprising at least 3 polymorphisms selected from Table 1, and (ii) detecting the genotype in the sample obtained from the subject; (c) if it is determined that the subject does not have non - response or loss of response to the standard therapeutic agent or is not at risk of developing these, treating the subject by administering to the subject a therapeutically effective amount of the standard therapeutic agent; and (d) if it is determined that the subject has non - response or loss of response to the standard therapeutic agent or is at risk of developing these, and is determined to be suitable for treatment with an inhibitor of TL1A activity or expression, treating the subject by administering to the subject a therapeutically effective amount of an inhibitor of TL1A activity or expression. In some embodiments, the at least 3 polymorphisms are selected from the group consisting of rs11897732, rs6740739, rs17796285, rs7935393, rs12934476, rs12457255, rs2070557, rs4246905, rs10974900, rs12434976, rs16901748, rs2815844, rs889702, rs2409750, rs1541020, rs4942248, rs12934476, rs12457255, rs2297437, rs41309367, rs10733509, rs10750376, rs10932456, rs1326860, rs1528663, rs1892231, rs951279, rs9806914, rs7935393, rs1690492, rs420726, rs7759385, rs10974900, rs1326860, rs2548147, rs2815844, rs889702, rs9806914, rs6478109, rs7278257, and rs11221332.In some embodiments, one of the at least three polymorphisms comprises the minor allele provided in Table 1. In some embodiments, one of the at least three polymorphisms comprises the major allele provided in Table 1. In some embodiments, the genotype is heterozygous. In some embodiments, the genotype is homozygous.In some embodiments, at least three polymorphisms are selected from the group consisting of the "G" allele at rs11897732, the "A" allele at rs6740739, the "G" allele at rs17796285, the "A" allele at rs7935393, the "G" allele at rs12934476, the "A" allele at rs12457255, the "A" allele at rs2070557, the "A" allele at rs4246905, the "A" allele at rs10974900, the "C" allele at rs12434976, the "A" allele at rs16901748, the "A" allele at rs2815844, the "G" allele at rs889702, the "C" allele at rs2409750, the "A" allele at rs1541020, the "T" allele at rs4942248, the "G" allele at rs12934476, the "A" allele at rs12457255, the "A" allele at rs2297437, the "G" allele at rs41309367, the "A" allele at rs10733509, the "G" allele at rs10750376, the "G" allele at rs10932456, the "A" allele at rs1326860, the "G" allele at rs1528663, the "C" allele at rs1892231, the "A" allele at rs951279, the "A" allele at rs9806914, the "A" allele at rs7935393, the "G" allele at rs1690492, the "A" allele at rs420726, the "T" allele at rs7759385, the "A" allele at rs10974900, the "A" allele at rs1326860, the "C" allele at rs2548147, the "A" allele at rs2815844, the "G" allele at rs889702, the "A" allele at rs9806914, the "A" allele at rs6478109, the "C" allele at rs7278257, and the "A" allele at rs11221332. In some embodiments, at least three polymorphisms include imm_9_116608587, imm_11_127948309, and rs1892231.In some embodiments, at least three polymorphisms include imm_9_116608587, imm_11_127948309, and rs9806914. In some embodiments, at least three polymorphisms include imm_9_116608587, imm_11_127948309, and imm_21_44478192. In some embodiments, at least three polymorphisms include imm_9_116608587, imm_11_127948309, and imm_21_44479552. In some embodiments, at least three polymorphisms include imm_9_116608587, rs1892231, and rs9806914. In some embodiments, at least three polymorphisms include imm_9_116608587, rs1892231, and imm_21_44478192. In some embodiments, at least three polymorphisms include imm_9_116608587, rs1892231, and imm_21_44479552. In some embodiments, at least three polymorphisms include imm_9_116608587, rs9806914, and imm_21_44478192. In some embodiments, at least three polymorphisms include imm_9_116608587, rs9806914, and imm_21_44478192. In some embodiments, at least three polymorphisms include imm_9_116608587, imm_21_44478192, and imm_21_44479552. In some embodiments, at least three polymorphisms include imm_11_127948309, rs1892231, and rs9806914. In some embodiments, at least three polymorphisms include imm_11_127948309, rs1892231, and imm_21_44478192. In some embodiments, at least three polymorphisms include imm_11_127948309, rs1892231, and imm_21_44479552. In some embodiments, at least three polymorphisms include imm_11_127948309, rsrs9806914, and imm_21_44478192.In some embodiments, at least three polymorphs include imm_11_127948309, rsrs9806914, and imm_21_44479552. In some embodiments, at least three polymorphs include imm_11_127948309, imm_21_44478192, and imm_21_44479552. In some embodiments, at least three polymorphs include rs1892231, rs9806914, and imm_21_44478192. In some embodiments, at least three polymorphs include rs1892231, rs9806914, and imm_21_44478192. In some embodiments, at least three polymorphs include rs1892231, imm_21_44478192, and imm_21_44479552. In some embodiments, at least three polymorphs include rs9806914, imm_21_44478192, and imm_21_44479552. In some embodiments, the standard therapeutic agents are selected from the group consisting of glucocorticoids, anti-TNF therapies, anti-a4-b7 therapies (vedolizumab), anti-IL12p40 therapies (ustekinumab), thalidomide, and cytotoxins.

[0063] Additional aspects and advantages of the present disclosure will be readily apparent to those of ordinary skill in the art from the following detailed description, where only exemplary embodiments of the present disclosure are shown and described. As will be understood from the following description, the present disclosure is capable of other embodiments and of being practiced or carried out in various ways. Various details thereof can be modified in various obvious respects, all without departing from the present disclosure. Accordingly, the drawings and description are to be regarded as illustrative in nature and not as restrictive.

[0064] Incorporation by reference All publications, patents, and patent applications mentioned in this specification are hereby incorporated by reference into this specification 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 that the incorporated publications and patents or patent applications conflict with the disclosure contained herein, this specification is intended to supersede and / or precede such conflicting subject matter.

Brief Description of the Drawings

[0065] The novel features relating to the concepts of the present invention are specifically described together with the appended claims. The features and advantages of the present invention will be better understood by reference to the following detailed description which describes exemplary embodiments in which the principles of the present invention are used, and the following appended drawings (also referred to herein as “Figures” and “FIGs.”).

[0066]

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5A

Figure 5B

Figure 5C

Figure 6

Modes for Carrying Out the Invention

[0067] This specification provides 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 that the subject is a carrier of a genotype. The subject may be a patient who may be diagnosed with an inflammatory disease such as inflammatory bowel disease (IBD) or Crohn's disease (CD), a fibrostenotic disease, or a fibrotic disease. The subject may not be a patient having or suspected of having an inflammatory disease, a fibrostenotic disease, or a fibrotic disease. Optionally, the genotype may be useful for characterizing an inflammatory, fibrostenotic, or fibrotic disease or disorder mediated by TL1A. In some embodiments, the subject is treated by administration of an inhibitor of TL1A activity or expression (e.g., an anti - TL1A antibody), provided that the genotype is detected. Optionally, identifying that a subject is suitable for treatment with an inhibitor of activity or expression is required for administering the inhibitor to the subject.

[0068] Referring to FIG. 1, in some embodiments, the methods, systems, and kits of the present disclosure include a step (101) of providing a buccal swab sample from a subject, a step (102) of optionally purifying DNA from the sample by processing the sample, a step (103) of analyzing the optionally processed sample to detect the genotypes of at least three loci in the sample, a step (104) of processing the genotypes to generate a TNFSF15 profile, and a step (105) of selecting a treatment to treat a disease or disorder of the subject based on the TNFSF15 profile.

[0069] The genotypes described herein are detected using a suitable genotyping device (e.g., an array, sequencing). In some examples, the sample is obtained indirectly or directly from a subject or patient. In some examples, the sample can be obtained by the subject. In other examples, the sample can be obtained by a healthcare provider such as a nurse or doctor. The sample can be obtained from a body fluid or tissue that substantially contains genetic information such as blood.

[0070] The subjects disclosed herein can be mammals such as mice, rats, guinea pigs, rabbits, non-human primates, livestock, etc. In some examples, the subject is a human. In some examples, the subject has symptoms associated with the diseases or disorders disclosed herein (e.g., abdominal pain, cramps, diarrhea, rectal bleeding, fever, weight loss, fatigue, loss of appetite, dehydration symptoms, and nutritional disorders, anemia, or ulcers).

[0071] In some embodiments, the subject is sensitive to thiopurine toxicity or diseases caused by thiopurine toxicity (such as pancreatitis or leukopenia) or is troubled by them. The subject has experienced or is suspected of experiencing non-response or loss of response to standard treatments (e.g., anti-TNFα therapeutic agents, anti-a4-b7 therapeutic agents (vedolizumab), anti-IL12p40 therapeutic agents (ustekinumab), thalidomide, or cytotoxins).

[0072] The diseases or disorders disclosed in this specification may be inflammatory diseases, fibrostenotic diseases, or fibrotic diseases. In some examples, the disease or disorder is a TL1A-mediated disease or disorder. The term "TL1A-mediated disease or disorder" refers to the pathogenesis or etiology of a disease or disorder that is at least partially induced by TL1A signaling. In some examples, the disease or disorder is an immune-mediated disease or disorder such as those mediated by TL1A.

[0073] In some embodiments, the disease or disorder is an inflammatory disease or disorder that is at least partially mediated by TL1A signaling. Non-limiting examples of inflammatory diseases include allergies, ankylosing spondylitis, asthma, atopic dermatitis, autoimmune diseases or disorders, cancer, celiac disease, chronic obstructive pulmonary disease (COPD), chronic peptic ulcers, cystic fibrosis of the pancreas, diabetes (e.g., type 1 and type 2 diabetes), glomerulonephritis, gout, hepatitis (e.g., active hepatitis), immune-mediated diseases or disorders, inflammatory bowel diseases (IBD) such as Crohn's disease and ulcerative colitis, myositis, osteoarthritis, pelvic inflammatory disease (PID), multiple sclerosis, neurodegenerative diseases due to aging, periodontal abscess (e.g., periapical periodontitis), preperfusion injury transplant rejection, psoriasis, pulmonary fibrosis, rheumatic diseases, scleroderma, rhinitis, tuberculosis.

[0074] In some embodiments, the disease or disorder is an autoimmune disease that is at least partially mediated by TL1A signaling. Non-limiting examples of autoimmune diseases or disorders include achalasia, Addison's disease, adult Still's disease, agammaglobulinemia, alopecia areata, amyloidosis, ankylosing spondylitis, anti-GBM / anti-TBM nephritis, antiphospholipid antibody syndrome, autoimmune angioedema, autoimmune autonomic neuropathy, autoimmune encephalomyelitis, autoimmune hepatitis, autoimmune inner ear disease (AIED), autoimmune myocarditis, autoimmune oophoritis, autoimmune orchitis, autoimmune pancreatitis, autoimmune retinopathy, autoimmune urticaria, axonal neuropathy of neurons (AMAN), Balo disease, Behçet's disease, benign mucous membrane 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 with polyangiitis (EGPA), cicatricial pemphigoid, Cogan syndrome, cold agglutinin disease, congenital heart block, coxsackievirus myocarditis, CREST syndrome, Crohn's disease, dermatitis herpetiformis, dermatomyositis, Devic's disease (neuromyelitis optica), discoid lupus, Dressler 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 syndrome, granulomatosis with polyangiitis, Graves' disease, Guillain-Barré syndrome, Hashimoto's thyroiditis, hemolytic anemia, Henoch-Schönlein purpura (HSP), herpes gestationis or pemphigoid gestationis (PG), hidradenitis suppurativa (HS) (opposite type acne), hypogammaglobulinemia, IgA nephropathy, IgG4-related sclerosing diseases, 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, Meniere's disease, microscopic polyangiitis (MPA), mixed connective tissue disease (MCTD), Mooren ulcer, Mucha-Habermann disease, multifocal motor neuropathy (MMN) or MMNCB, multiple sclerosis,Myasthenia gravis, myositis, narcolepsy, neonatal lupus, neuromyelitis optica, neutropenia, cicatricial pemphigoid of the eye, optic neuritis, palindromic rheumatism (PR), PANDAS, paraneoplastic cerebellar degeneration (PCD), paroxysmal nocturnal hemoglobinuria (PNH), Parry-Romberg syndrome, pars planitis (peripheral uveitis), Persistent-Turner syndrome, pemphigus, peripheral neuropathy, perivenous encephalomyelitis, pernicious anemia (PA), POEMS syndrome, polyarteritis nodosa, polyglandular syndrome type I, type II, type III, rheumatoid polymyalgia, polymyositis, post-myocardial infarction syndrome, post-pericardiotomy 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, Sjögren's syndrome, autoimmune sperm and testicular autoimmunity, stiff person syndrome (SPS), subacute bacterial endocarditis (SBE), Susac syndrome, sympathetic ophthalmia (SO), Takayasu arteritis, temporal arteritis / giant cell arteritis, thrombotic 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 are mentioned.

[0075] In some embodiments, the disease or disorder is cancer that is at least partially mediated by TL1A signaling. Non-limiting examples of cancer include adenoid cystic carcinoma, adrenocortical carcinoma, amyloidosis, anal cancer, ataxia telangiectasia, dysplastic nevus syndrome, basal cell carcinoma, bile duct cancer, Birt-Hogg-Dubé syndrome, bladder cancer, bone cancer, brain tumor, breast cancer, male breast cancer, 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, acute lymphoblastic leukemia, acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), adult leukemia, pediatric leukemia, chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), liver cancer, lobular carcinoma, lung cancer, small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), Hodgkin lymphoma, non-Hodgkin lymphoma, malignant glioma, melanoma, meningioma, multiple myeloma, myelodysplastic syndrome (MDS), nasopharyngeal cancer, neuroendocrine tumor, oral cancer, osteosarcoma, ovarian cancer, pancreatic cancer, pancreatic neuroendocrine tumor, parathyroid cancer, penile cancer, peritoneal cancer, Peutz-Jeghers syndrome, pituitary tumor, primary erythrocytosis, prostate cancer, renal cell carcinoma, retinoblastoma, salivary gland cancer, sarcoma, Kaposi sarcoma, skin cancer, small intestine cancer, stomach cancer, testicular cancer, thymoma, thyroid cancer, uterine (endometrial) cancer, vaginal cancer, and Wilms tumor.

[0076] In some embodiments, the disease or disorder is an inflammatory bowel disease such as Crohn's disease (CD) or ulcerative colitis (UC). The subject may have fibrosis, fibrotic stricture, or a fibrotic disorder, separately from or in combination with the inflammatory disease. Optionally, the CD is severe CD. Severe CD may result from inflammation that causes scar tissue formation (fibrotic stricture) and / or swelling of the intestinal wall. Optionally, CD is characterized by the presence of fibrotic and / or inflammatory strictures. Such strictures can be detected by computed tomography enterography (CTE) and magnetic resonance enterography (MRE). The disease or disorder can optionally be characterized as refractory, where the disease is resistant to standard treatments (e.g., anti-TNFα therapy). Non-limiting examples of standard treatments include glucocorticosteroids, anti-TNF therapy, anti-α4-β7 therapy (vedolizumab), anti-IL12p40 therapy (ustekinumab), thalidomide, and cytokines.

[0077] Genotype Disclosed herein are genotypes that can be detected in a sample obtained from a subject by analyzing the genetic material in the sample. In some examples, the subject may be human. In some embodiments, the genetic material is obtained from a subject having a disease or disorder disclosed herein. Optionally, the genetic material is obtained from blood, serum, plasma, sweat, hair, tears, urine, by techniques known to those of skill in the art. Optionally, the genetic material is obtained by biopsy, e.g., from the digestive tract of the subject.

[0078] The genotypes of the present disclosure include genetic material that is deoxyribonucleic acid (DNA). In some examples, the genotype includes denatured DNA molecules or fragments thereof. In some examples, the genotype includes 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 examples, the DNA is single-stranded DNA (ssDNA), double-stranded DNA, denatured double-stranded DNA, synthetic DNA, and combinations thereof. The circular DNA may be cleaved or fragmented.

[0079] The genotypes disclosed herein include at least one polymorphism in the genes or genetic loci described herein. In some examples, the gene or genetic locus is 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 (MTMR9), ETS Proto-Oncogene, 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), Fox-1 Homolog 1 (RBFOX1), RNA Binding Motif Protein 17 (RBM17), 6-Phosphofructo-2-Kinase / Fructose-2,Selected from the group consisting of 6-phosphofructo-2-kinase 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 Acid Acyl-CoA Reductase 1 (FAR1), Spondin 1 (SPON1), Plexin A2 (PLXNA2), MIR205 Host Gene (MIR205HG), C-Type Lectin Domain Containing 16A (CLEC16A), PR / SET Domain 14 (PRDM), Autophagy Related 5 (ATG5), and Prostaglandin E Receptor 4 (PTGER4). In some examples, the gene or locus comprises the gene or locus provided in Table 1. The genotypes disclosed herein are optionally haplotypes. In some examples, the genotype comprises a specific polymorphism, a polymorphism in linkage disequilibrium (LD), or a combination thereof. Optionally, the LD is defined by an R of at least or about 0.70, 0.75, 0.80, 0.85, 0.90, or 1.0. 2 The genotypes disclosed herein may 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 a preferred embodiment, the genotypes disclosed herein comprise a combination of three polymorphisms such as those provided in Table 1.

[0080] The polymorphisms described herein may be single nucleotide polymorphisms or indels (insertions / deletions). In some examples, the polymorphism is an insertion or deletion of at least one nucleic acid base (e.g., an indel). In some examples, the genotype may include a copy number variation (CNV), which is a variation in many nucleic acid sequences among individuals in a given population. In some examples, the CNV includes at least or about 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, or 50 nucleic acid molecules. In some examples, the genotype is heterozygous. In some examples, the genotype is homozygous.

[0081] Described herein, in the following embodiments, are the genotypes disclosed herein: 1. A genotype comprising at least one polymorphism in a gene or locus. 2. The genotype according to embodiment 1, comprising the polymorphisms provided in Table 1. 3. The genotype according to any one of embodiments 1 to 2, which is heterozygous. 4. The genotype according to any one of embodiments 1 to 2, which is homozygous. 5. The genotype according to any one of embodiments 1 to 4, comprising at least two polymorphisms. 6. The genotype according to any one of embodiments 1 to 4, comprising at least three polymorphisms. 7. The genotype according to any one of embodiments 1 to 4, comprising at least four polymorphisms. 8. The genotype according to embodiment 1, comprising a polymorphism in linkage disequilibrium with the polymorphisms provided in Table 1. 9. The genotype according to embodiment 8, wherein the LD is defined by (i) a D’ value of at least about 0.70, or (ii) a D’ value of 0 and an r 2 value of at least about 0.70. 10. The genotype according to embodiment 8, wherein the LD is defined by (i) a D’ value of at least about 0.80, or (ii) a D’ value of 0 and an r 2 value of at least about 0.80. 11. The LD is (i) a D’ value of at least about 0.90, or (ii) a D’ value of 0 and an r of at least about 0.902 The genotype according to Embodiment 8, defined by the value. 12. LD is (i) a D’ value of at least about 0.95, or (ii) a D’ value of 0 and an r of at least about 0.95 2 The genotype according to Embodiment 8, defined by the value. 13. The gene or locus is 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 (MTMR9), ETS Proto-Oncogene, 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), Fox-1 Homolog 1 (RBFOX1), RNA Binding Motif Protein 17 (RBM17), 6-Phosphofructo-2-Kinase / Fructose-2,The genotype according to any one of Embodiments 1 to 12, selected from the group consisting of 6 - bisphosphatase 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 Acid Acyl - CoA Reductase 1 (FAR1), Spondin 1 (SPON1), Plexin A2 (PLXNA2), MIR205 Host Gene (MIR205HG), C - Type Lectin Domain Containing 16A (CLEC16A), PR / SET Domain 14 (PRDM), Autophagy Related 5 (ATG5), and Prostaglandin E Receptor 4 (PTGER4). 14. (1) rs16901748, rs7759385, rs4246905, (2) rs16901748, rs7759385, rs7935393, (3) rs16901748, rs7759385, rs1892231, (4) rs16901748, rs7759385, rs12934476, (5) rs16901748, rs7759385, rs9806914, (6) rs16901748, rs7759385, rs2297437, (7) rs16901748, rs7759385, rs2070557, (8) rs16901748, rs7759385, rs7278257, (9) rs16901748, rs7759385, rs11221332, (10) rs16901748, rs7759385, rs41309367, (11) rs16901748, rs7759385, rs6478109, (12) rs16901748, rs4246905, rs7935393, (13) rs16901748, rs4246905, rs1892231, (14) rs16901748, rs4246905, rs12934476, (15) rs16901748, rs4246905, rs9806914, (16) rs16901748, rs4246905, rs2297437, (17) rs16901748, rs4246905, rs2070557, (18) rs16901748, rs4246905, rs7278257, (19) rs16901748, rs4246905, rs11221332, (20) rs16901748, rs4246905, rs41309367, (21) rs16901748, rs4246905, rs6478109, (22) rs16901748, rs7935393, rs1892231, (23) rs16901748, rs7935393, rs12934476, (24) rs16901748, rs7935393, rs9806914, (25) rs16901748, rs7935393, rs2297437, (26) rs16901748, rs7935393, rs2070557, (27) rs16901748, rs7935393, rs7278257, (28) rs16901748, rs7935393, rs11221332, (29) rs16901748, rs7935393, rs41309367, (30) rs16901748, rs7935393, rs6478109, (31) rs16901748, rs1892231, rs12934476, (32) rs16901748, rs1892231, rs9806914, (33) rs16901748, rs1892231, rs2297437, (34) rs16901748, rs1892231, rs2070557, (35) rs16901748, rs1892231, rs7278257, (36) rs16901748, rs1892231, rs11221332, (37) rs16901748, rs1892231, rs41309367, (38) rs16901748, rs1892231, rs6478109, (39) rs16901748, rs12934476, rs9806914, (40) rs16901748, rs12934476, rs2297437, (41) rs16901748, rs12934476, rs2070557, (42) rs16901748, rs12934476, rs7278257, (43) rs16901748, rs12934476, rs11221332, (44) rs16901748, rs12934476, rs41309367, (45) rs16901748, rs12934476, rs6478109, (46) rs16901748, rs9806914, rs2297437, (47) rs16901748, rs9806914, rs2070557, (48) rs16901748, rs9806914, rs7278257, (49) rs16901748, rs9806914, rs11221332, (50) rs16901748, rs9806914, rs41309367, (51) rs16901748, rs9806914, rs6478109, (52) rs16901748, rs2297437, rs2070557, (53) rs16901748, rs2297437, rs7278257, (54) rs16901748, rs2297437, rs11221332, (55) rs16901748, rs2297437, rs41309367, (56) rs16901748, rs2297437, rs6478109, (57) rs16901748, rs2070557, rs7278257, (58) rs16901748, rs2070557, rs11221332, (59) rs16901748, rs2070557, rs41309367, (60) rs16901748, rs2070557, rs6478109, (61) rs16901748, rs7278257, rs11221332, (62) rs16901748, rs7278257, rs41309367, (63) rs16901748, rs7278257, rs6478109, (64) rs16901748, rs11221332, rs41309367, (65) rs16901748, rs11221332, rs6478109, (66) rs16901748, rs41309367, rs6478109, (67) rs7759385, rs4246905, rs7935393, (68) rs7759385, rs4246905, rs1892231, (69) rs7759385, rs4246905, rs12934476, (70) rs7759385, rs4246905, rs9806914, (71) rs7759385, rs4246905, rs2297437, (72) rs7759385, rs4246905, rs2070557, (73) rs7759385, rs4246905, rs7278257, (74) rs7759385, rs4246905, rs11221332, (75) rs7759385, rs4246905, rs41309367, (76) rs7759385, rs4246905, rs6478109, (77) rs7759385, rs7935393, rs1892231, (78) rs7759385, rs7935393, rs12934476, (79) rs7759385, rs7935393, rs9806914, (80) rs7759385, rs7935393, rs2297437, (81) rs7759385, rs7935393, rs2070557, (82) rs7759385, rs7935393, rs7278257, (83) rs7759385, rs7935393, rs11221332, (84) rs7759385, rs7935393, rs41309367, (85) rs7759385, rs7935393, rs6478109, (86) rs7759385, rs1892231, rs12934476, (87) rs7759385, rs1892231, rs9806914, (88) rs7759385, rs1892231, rs2297437, (89) rs7759385, rs1892231, rs2070557, (90) rs7759385, rs1892231, rs7278257, (91) rs7759385, rs1892231, rs11221332, (92) rs7759385, rs1892231, rs41309367, (93) rs7759385, rs1892231, rs6478109, (94) rs7759385, rs12934476, rs9806914, (95) rs7759385, rs12934476, rs2297437, (96) rs7759385, rs12934476, rs2070557, (97) rs7759385, rs12934476, rs7278257, (98) rs7759385, rs12934476, rs11221332, (99) rs7759385, rs12934476, rs41309367, (100) rs7759385, rs12934476, rs6478109, (101) rs7759385, rs9806914, rs2297437, (102) rs7759385, rs9806914, rs2070557, (103) rs7759385, rs9806914, rs7278257, (104) rs7759385, rs9806914, rs11221332, (105) rs7759385, rs9806914, rs41309367, (106) rs7759385, rs9806914, rs6478109, (107) rs7759385, rs2297437, rs2070557, (108) rs7759385, rs2297437, rs7278257, (109) rs7759385, rs2297437, rs11221332, (110) rs7759385, rs2297437, rs41309367, (111) rs7759385, rs2297437, rs6478109, (112) rs7759385, rs2070557, rs7278257, (113) rs7759385, rs2070557, rs11221332, (114) rs7759385, rs2070557, rs41309367, (115) rs7759385, rs2070557, rs6478109, (116) rs7759385, rs7278257, rs11221332, (117) rs7759385, rs7278257, rs41309367, (118) rs7759385, rs7278257, rs6478109, (119) rs7759385, rs11221332, rs41309367, (120) rs7759385, rs11221332, rs6478109, (121) rs7759385, rs41309367, rs6478109, (122) rs4246905, rs7935393, rs1892231, (123) rs4246905, rs7935393, rs12934476, (124) rs4246905, rs7935393, rs9806914, (125) rs4246905, rs7935393, rs2297437, (126) rs4246905, rs7935393, rs2070557, (127) rs4246905, rs7935393, rs7278257, (128) rs4246905, rs7935393, rs11221332, (129) rs4246905, rs7935393, rs41309367, (130) rs4246905, rs7935393, rs6478109, (131) rs4246905, rs1892231, rs12934476, (132) rs4246905, rs1892231, rs9806914, (133) rs4246905, rs1892231, rs2297437, (134) rs4246905, rs1892231, rs2070557, (135) rs4246905, rs1892231, rs7278257, (136) rs4246905, rs1892231, rs11221332, (137) rs4246905, rs1892231, rs41309367, (138) rs4246905, rs1892231, rs6478109, (139) rs4246905, rs12934476, rs9806914, (140) rs4246905, rs12934476, rs2297437, (141) rs4246905, rs12934476, rs2070557, (142) rs4246905, rs12934476, rs7278257, (143) rs4246905, rs12934476, rs11221332, (144) rs4246905, rs12934476, rs41309367, (145) rs4246905, rs12934476, rs6478109, (146) rs4246905, rs9806914, rs2297437, (147) rs4246905, rs9806914, rs2070557, (148) rs4246905, rs9806914, rs7278257, (149) rs4246905, rs9806914, rs11221332, (150) rs4246905, rs9806914, rs41309367, (151) rs4246905, rs9806914, rs6478109, (152) rs4246905, rs2297437, rs2070557, (153) rs4246905, rs2297437, rs7278257, (154) rs4246905, rs2297437, rs11221332, (155) rs4246905, rs2297437, rs41309367, (156) rs4246905, rs2297437, rs6478109, (157) rs4246905, rs2070557, rs7278257, (158) rs4246905, rs2070557, rs11221332, (159) rs4246905, rs2070557, rs41309367, (160) rs4246905, rs2070557, rs6478109, (161) rs4246905, rs7278257, rs11221332, (162) rs4246905, rs7278257, rs41309367, (163) rs4246905, rs7278257, rs6478109, (164) rs4246905, rs11221332, rs41309367, (165) rs4246905, rs11221332, rs6478109, (166) rs4246905, rs41309367, rs6478109, (167) rs7935393, rs1892231, rs12934476, (168) rs7935393, rs1892231, rs9806914, (169) rs7935393, rs1892231, rs2297437, (170) rs7935393, rs1892231, rs2070557, (171) rs7935393, rs1892231, rs7278257, (172) rs7935393, rs1892231, rs11221332, (173) rs7935393, rs1892231, rs41309367, (174) rs7935393, rs1892231, rs6478109, (175) rs7935393, rs12934476, rs9806914, (176) rs7935393, rs12934476, rs2297437, (177) rs7935393, rs12934476, rs2070557, (178) rs7935393, rs12934476, rs7278257, (179) rs7935393, rs12934476, rs11221332, (180) rs7935393, rs12934476, rs41309367, (181) rs7935393, rs12934476, rs6478109, (182) rs7935393, rs9806914, rs2297437, (183) rs7935393, rs9806914, rs2070557, (184) rs7935393, rs9806914, rs7278257, (185) rs7935393, rs9806914, rs11221332, (186) rs7935393, rs9806914, rs41309367, (187) rs7935393, rs9806914, rs6478109, (188) rs7935393, rs2297437, rs2070557, (189) rs7935393, rs2297437, rs7278257, (190) rs7935393, rs2297437, rs11221332, (191) rs7935393, rs2297437, rs41309367, (192) rs7935393, rs2297437, rs6478109, (193) rs7935393, rs2070557, rs7278257, (194) rs7935393, rs2070557, rs11221332, (195) rs7935393, rs2070557, rs41309367, (196) rs7935393, rs2070557, rs6478109, (197) rs7935393, rs7278257, rs11221332, (198) rs7935393, rs7278257, rs41309367, (199) rs7935393, rs7278257, rs6478109, (200) rs7935393, rs11221332, rs41309367, (201) rs7935393, rs11221332, rs6478109, (202) rs7935393, rs41309367, rs6478109, (203) rs1892231, rs12934476, rs9806914, (204) rs1892231, rs12934476, rs2297437, (205) rs1892231, rs12934476, rs2070557, (206) rs1892231, rs12934476, rs7278257, (207) rs1892231, rs12934476, rs11221332, (208) rs1892231, rs12934476, rs41309367, (209) rs1892231, rs12934476, rs6478109, (210) rs1892231, rs9806914, rs2297437, (211) rs1892231, rs9806914, rs2070557, (212) rs1892231, rs9806914, rs7278257, (213) rs1892231, rs9806914, rs11221332, (214) rs1892231, rs9806914, rs41309367, (215) rs1892231, rs9806914, rs6478109, (216) rs1892231, rs2297437, rs2070557, (217) rs1892231, rs2297437, rs7278257, (218) rs1892231, rs2297437, rs11221332, (219) rs1892231, rs2297437, rs41309367, (220) rs1892231, rs2297437, rs6478109, (221) rs1892231, rs2070557, rs7278257, (222) rs1892231, rs2070557, rs11221332, (223) rs1892231, rs2070557, rs41309367, (224) rs1892231, rs2070557, rs6478109, (225) rs1892231, rs7278257, rs11221332, (226) rs1892231, rs7278257, rs41309367, (227) rs1892231, rs7278257, rs6478109, (228) rs1892231, rs11221332, rs41309367, (229) rs1892231, rs11221332, rs6478109, (230) rs1892231, rs41309367, rs6478109, (231) rs12934476, rs9806914, rs2297437, (232) rs12934476, rs9806914, rs2070557, (233) rs12934476, rs9806914, rs7278257, (234) rs12934476, rs9806914, rs11221332, (235) rs12934476, rs9806914, rs41309367, (236) rs12934476, rs9806914, rs6478109, (237) rs12934476, rs2297437, rs2070557, (238) rs12934476, rs2297437, rs7278257, (239) rs12934476, rs2297437, rs11221332, (240) rs12934476, rs2297437, rs41309367, (241) rs12934476, rs2297437, rs6478109, (242) rs12934476, rs2070557, rs7278257, (243) rs12934476, rs2070557, rs11221332, (244) rs12934476, rs2070557, rs41309367, (245) rs12934476, rs2070557, rs6478109, (246) rs12934476, rs7278257, rs11221332, (247) rs12934476, rs7278257, rs41309367, (248) rs12934476, rs7278257, rs6478109, (249) rs12934476, rs11221332, rs41309367, (250) rs12934476, rs11221332, rs6478109, (251) rs12934476, rs41309367, rs6478109, (252) rs9806914, rs2297437, rs2070557, (253) rs9806914, rs2297437, rs7278257, (254) rs9806914, rs2297437, rs11221332, (255) rs9806914, rs2297437, rs41309367, (256) rs9806914, rs2297437, rs6478109, (257) rs9806914, rs2070557, rs7278257, (258) rs9806914, rs2070557, rs11221332, (259) rs9806914, rs2070557, rs41309367, (260) rs9806914, rs2070557, rs6478109, (261) rs9806914, rs7278257, rs11221332, (262) rs9806914, rs7278257, rs41309367, (263) rs9806914, rs7278257, rs6478109, (264) rs9806914, rs11221332, rs41309367, (265) rs9806914, rs11221332, rs6478109, (266) rs9806914, rs41309367, rs6478109, (267) rs2297437, rs2070557, rs7278257, (268) rs2297437, rs2070557, rs11221332, (269) rs2297437, rs2070557, rs41309367, (270) rs2297437, rs2070557, rs6478109, (271) rs2297437, rs7278257, rs11221332, (272) rs2297437, rs7278257, rs41309367, (273) rs2297437, rs7278257, rs6478109, (274) rs2297437, rs11221332, rs41309367, (275) rs2297437, rs11221332, rs6478109, (276) rs2297437, rs41309367, rs6478109, (277) rs2070557, rs7278257, rs11221332, (278) rs2070557, rs7278257, rs41309367, (279) rs2070557, rs7278257, rs6478109, (280) rs2070557, rs11221332, rs41309367, (281) rs2070557, rs11221332, rs6478109, (282) rs2070557, rs41309367, rs6478109, (283) rs7278257, rs11221332, rs41309367, (284) rs7278257, rs11221332, rs6478109, (285) rs7278257, rs41309367, rs6478109, or (286) rs11221332, rs41309367, rs6478109 The genotype according to any one of Embodiments 5 to 6, comprising at least two polymorphisms selected from 15. The genotype according to Embodiment 14, wherein said rs7278257 is replaced by rs56124762. 16. The genotype according to Embodiment 14, wherein said rs7278257 is replaced by rs2070558. 17. The genotype according to Embodiment 14, wherein said rs7278257 is replaced by rs2070561. 27. A genotype according to any one of embodiments 5 to 6, comprising at least two polymorphisms selected from imm_9_116608587, imm_11_127948309, and rs1892231. 28. A genotype according to any one of embodiments 5 to 6, comprising at least two polymorphisms selected from imm_9_116608587, imm_11_127948309, and rs9806914. 29. A genotype according to any one of embodiments 5 to 6, comprising at least two polymorphisms selected from imm_9_116608587, imm_11_127948309, and imm_21_44478192. 30. A genotype according to any one of embodiments 5 to 6, comprising at least two polymorphisms selected from imm_9_116608587, imm_11_127948309, and imm_21_44479552. 31. A genotype according to any one of embodiments 5 to 6, comprising at least two polymorphisms selected from imm_9_116608587, rs1892231, and rs9806914. 32. A genotype according to any one of embodiments 5 to 6, comprising at least two polymorphisms selected from imm_9_116608587, rs1892231, and imm_21_44478192. 33. A genotype according to any one of embodiments 5 to 6, comprising at least two polymorphisms selected from imm_9_116608587, rs1892231, and imm_21_44479552. 34. A genotype according to any one of embodiments 5 to 6, comprising at least two polymorphisms selected from imm_9_116608587, rs9806914, and imm_21_44478192. 35. A genotype according to any one of embodiments 5 to 6, comprising at least two polymorphisms selected from imm_9_116608587, rs9806914, and imm_21_44479552. The genotype according to any one of embodiments 5 to 6, comprising at least two polymorphisms selected from imm_9_116608587, imm_21_44478192, and imm_21_44479552. The genotype according to any one of embodiments 5 to 6, comprising at least two polymorphisms selected from imm_11_127948309, rs1892231, and rs9806914. The genotype according to any one of embodiments 5 to 6, comprising at least two polymorphisms selected from imm_11_127948309, rs1892231, and imm_21_44478192. The genotype according to any one of embodiments 5 to 6, comprising at least two polymorphisms selected from imm_11_127948309, rs1892231, and imm_21_44479552. The genotype according to any one of embodiments 5 to 6, comprising at least two polymorphisms selected from imm_11_127948309, rs9806914, and imm_21_44478192. The genotype according to any one of embodiments 5 to 6, comprising at least two polymorphisms selected from imm_11_127948309, rs9806914, and imm_21_44479552. The genotype according to any one of embodiments 5 to 6, comprising at least two polymorphisms selected from imm_11_127948309, imm_21_44478192, and imm_21_44479552. The genotype according to any one of embodiments 5 to 6, comprising at least two polymorphisms selected from rs1892231, rs9806914, and imm_21_44478192. The genotype according to any one of embodiments 5 to 6, comprising at least two polymorphisms selected from rs1892231, rs9806914, and imm_21_44479552. The genotype according to any one of Embodiments 5 to 6, comprising at least two polymorphisms selected from rs1892231, imm_21_44478192, and imm_21_44479552. The genotype according to any one of Embodiments 5 to 6, comprising at least two polymorphisms selected from rs9806914, imm_21_44478192, and imm_21_44479552. The genotype according to any one of Embodiments 5 to 6, comprising at least two polymorphisms selected from rs6478109, rs56124762, and rs1892231. The genotype according to any one of Embodiments 5 to 6, comprising at least two polymorphisms selected from rs6478109, rs56124762, and rs16901748. The genotype according to any one of Embodiments 5 to 6, comprising at least two polymorphisms selected from rs6478109, rs1892231, and rs16901748. The genotype according to any one of Embodiments 5 to 6, comprising at least two polymorphisms selected from rs56124762, rs1892231, and rs16901748. The genotype according to any one of Embodiments 5 to 6, comprising at least two polymorphisms selected from rs6478109, rs2070558, and rs1892231. The genotype according to any one of Embodiments 5 to 6, comprising at least two polymorphisms selected from rs6478109, rs2070558, and rs16901748. The genotype according to any one of Embodiments 5 to 6, comprising at least two polymorphisms selected from rs6478109, rs1892231, and rs16901748. The genotype according to any one of Embodiments 5 to 6, comprising at least two polymorphisms selected from rs2070558, rs1892231, and rs16901748. The genotype according to any one of embodiments 5 to 6, comprising at least two polymorphisms selected from rs6478109, rs2070561, and rs1892231. 47. The genotype according to any one of embodiments 5 to 6, comprising at least two polymorphisms selected from rs6478109, rs2070561, and rs16901748. 48. The genotype according to any one of embodiments 5 to 6, comprising at least two polymorphisms selected from rs6478109, rs1892231, and rs16901748. 49. The genotype according to any one of embodiments 5 to 6, comprising at least two polymorphisms selected from rs2070561, rs1892231, and rs16901748. 50. The genotype according to any one of embodiments 1 to 49, comprising the minor allele provided in Table 1 for at least one polymorphism. 51. The genotype according to any one of embodiments 1 to 49, comprising the major allele provided in Table 1 for at least one polymorphism. 52. The presence of the genotype predicts a positive therapeutic response to treatment with an inhibitor of TL1A activity or expression with 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%. The genotype according to any one of embodiments 1 to 51. 53. The presence of the genotype predicts a positive therapeutic response to treatment with an inhibitor of TL1A activity or 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%. The genotype according to any one of embodiments 1 to 55.

[0082] Aspects disclosed herein relate to and provide a genotype of a subject having or suspected of having a particular disease or disorder, or a subclinical phenotype thereof. In addition, genotypes disclosed herein are associated with an increase in TNFSF15 (TL1A) expression or activity. Thus, the genotype indicates that the subject has a positive therapeutic response to an inhibitor of TL1A activity or expression. Table 1 provides exemplary polymorphisms associated with and predictive of a positive therapeutic response to an inhibitor of TNFSF15 (TL1A) expression or activity. The term "positive therapeutic response" refers to a reduction or elimination of at least one symptom of a disease or disorder (e.g., Crohn's disease) after induction of treatment (e.g., an anti-TL1A antibody).

[0083]

Table 1-1

[0084]

Table 1-2

[0085] The present disclosure provides a model that includes three polymorphisms (e.g., a "3-SNP model") that indicate a positive therapeutic response of a subject to treatment with an inhibitor of TL1A activity or expression upon detection in a sample obtained from the subject. Non-limiting examples of models described herein include Model A (rs6478109, rs7278257, and rs1892231), Model B (rs6478109, rs2070557, and rs9806914), Model C (rs6478109, rs7935393, and rs1892231), Model D (rs6478109, rs7935393, and rs9806914), Model E (rs6478109, rs9806914, and rs16901748), Model F (rs6478109, rs16901748, and rs2297437), Model G (rs6478109, rs1892231, and rs16901748), Model H (rs6478109, rs2070557, and rs7935393), Model I (rs6478109, rs7278257, and rs7935393), Model J (rs6478109, rs9806914, and rs1892231), and Model K (rs6478109, rs7278257, and rs16901748).

[0086] Method Detection method The methods disclosed herein for detecting a genotype in a sample of a subject include the step of analyzing the genetic material in the sample to detect at least one of the presence, absence, and amount of a nucleic acid sequence encompassing the genotype of the subject. In some embodiments, the sample is analyzed to measure the presence, absence, or amount of at least three polymorphisms. In some embodiments, the sample is analyzed to measure the presence, absence, or amount of at least four polymorphisms. In some embodiments, the sample is analyzed to measure the presence, absence, or amount of at least five polymorphisms. In some embodiments, at least three genotypes are detected using the methods described herein.

[0087] Optionally, the nucleic acid sequence includes DNA. In some examples, the nucleic acid sequence includes a denatured DNA molecule or a fragment thereof. In some examples, the nucleic acid sequence includes 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 examples, the DNA is single-stranded DNA (ssDNA), double-stranded DNA, denatured double-stranded DNA, synthetic DNA, and combinations thereof. The circular DNA may be cleaved or fragmented. In some examples, the nucleic acid sequence includes RNA. In some examples, the nucleic acid sequence includes fragmented RNA. In some examples, the nucleic acid sequence includes partially degraded RNA. In some examples, the nucleic acid sequence includes microRNA or a portion thereof. In some examples, the nucleic acid sequence includes an RNA molecule or a fragmented RNA molecule (RNA fragment) selected from microRNA (miRNA), pre-miRNA, pri-miRNA, mRNA, pre-mRNA, viral RNA, viroid RNA, virusoid RNA, circular RNA (circRNA), ribosomal RNA (rRNA), transfer RNA (tRNA), pre-tRNA, long non-coding RNA (lncRNA), small nuclear RNA (snRNA), circulating RNA, cell-free RNA, exosomal RNA, vector-expressed RNA, RNA transcript, synthetic RNA, and combinations thereof.

[0088] Nucleic acid-based detection techniques that may be useful in the methods herein include quantitative polymerase chain reaction (qPCR), gel electrophoresis, in situ hybridization such as fluorescence in situ hybridization (FISH), cytochemistry, and next-generation sequencing. In some embodiments, the method includes TaqMan™ qPCR. This involves a nucleic acid amplification reaction with a specific primer pair and hybridization of the amplified nucleic acid with a hydrolyzable probe specific for the target nucleic acid.

[0089] In some examples, the method includes hybridization and / or amplification assays including, but not limited to, Southern or Northern blot analysis, polymerase chain reaction analysis, and probe arrays. Non-limiting amplification reactions include qPCR, self-sustained sequence replication, transcription amplification systems, Q-β replicase, rolling circle replication, or any other nucleic acid amplification known in the art. As discussed, reference to qPCR herein includes the use of the TaqMan™ method. Further exemplary hybridization assays include the use of nucleic acid probes conjugated to beads, multiwell plates, or other substrates, or immobilized by other means, where the nucleic acid probes are configured to hybridize to the target nucleic acid sequences of the genotypes provided herein. Non-limiting methods are those utilized in Anal Chem. 2013 Feb 5;85(3):1932-9.

[0090] In some embodiments, detection of the presence or absence of a genotype includes sequencing the genetic material of the subject. Sequencing can be performed by any suitable sequencing technique including, but not limited to, single molecule real time (SMRT) sequencing, polony sequencing, ligation sequencing, 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 modern sequencing techniques such as next generation sequencing, e.g., Illumina sequencing (e.g., Solexa), Roche 454 sequencing, Ion torrent sequencing, and SOLiD sequencing. Optionally, next generation sequencing requires high throughput sequencing methods. Additional sequencing methods available to those of skill in the art may be utilized.

[0091] In some examples, the number of nucleotides sequenced is 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 examples, the number of nucleotides sequenced is in the 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.

[0092] Exemplary probes include the nucleic acid sequence of at least 10 adjacent nucleic acids provided in any one of SEQ ID NOs: 1 to 48 or 57 to 59, or its reverse complement, which contain nucleobases represented by non-nucleobase characters (e.g., R, N, S). In some examples, the probe can be used to detect the polymorphisms provided in Table 1, and this probe contains the nucleic acid sequence of at least 10 adjacent nucleic acids provided in the corresponding SEQ ID NO or its reverse complement, and the 10 adjacent nucleic acids contain the "risk allele" provided in Table 1 or its reverse complement at the nuclear position represented by non-nucleobase characters. In some embodiments, the probe has 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 to 48 or 57 to 59, or its reverse complement. In some examples, forward primers and reverse primers are used to amplify the target nucleic acid sequence. The forward primer and the reverse primer may contain a nucleic acid sequence adjacent to the risk allele provided in Table 1, corresponding to the nucleic acid sequence provided in any one of SEQ ID NOs: 1 to 48 or 57 to 59, or its reverse complement.

[0093] Examples of molecules used as probes include, but are not limited to, RNA and DNA. In some embodiments, the term "probe" with respect to nucleic acids refers to any molecule that can selectively bind to a specifically intended target nucleic acid sequence. In some examples, the probe is specifically designed to be labeled using, for example, a radioactive label, a fluorescent label, an enzyme, a chemiluminescent tag, a colorimetric quantification tag, or other labels or tags known in the art. In some examples, the fluorescent label includes a fluorophore. In some examples, the fluorophore is an aromatic or heteroaromatic compound. In some examples, the fluorophore is pyrene, anthracene, naphthalene, acridine, stilbene, benzoxazole, indole, benzindole, oxazole, thiazole, benzothiazole, canine, carbocyanine, salicylate, anthranilate, xanthene, dye, coumarin. Exemplary xanthene dyes include, for example, fluorescein dyes and rhodamine dyes. Fluorescein dyes 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 naphthylamine dyes having an amino group at the α or β position. For example, naphthylamine compounds include 1-dimethylaminonaphthyl-5-sulfonate, 1-anilino-8-naphthalenesulfonate, and 2-p-toluidinyl-6-naphthalenesulfonate, 5-(2’-aminoethyl)aminonaphthalene-1-sulfonic acid (EDANS).Exemplary coumarins include, for example, 3-phenyl-7-isocyanatocoumarin; acridines such as 9-isothiocyanatoacridine and acridine orange; N-(p-(2-benzoxazolyl)phenyl)maleimide; cyanines such as indodicarbocyanine 3 (Cy3), indodicarbocyanine 5 (Cy5), 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-pyrrolidinyl)oxy]-6-oxohexyl]amino]sulfonyl]-4(or 2)-sulfophenyl]-2,3,6,7,12,13,16,17-octahydro-inner salt (TR or Texas Red); or BODIPY™ dyes. Optionally, the probe includes FAM as a dye label.

[0094] In some examples, the primers and / or probes described herein for detecting a target nucleic acid are used in an amplification reaction. In some examples, this amplification reaction is qPCR. A typical qPCR is a method that utilizes the TaqMan™ assay. Non-limiting examples of primer pairs useful for detecting one or more polymorphisms described herein are provided in Table 6 below.

[0095]

Table 2

[0096] In some examples, qPCR involves the use of 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 examples, the intercalating dye is SYBR.

[0097] In some examples, the number of amplification cycles for detecting a target nucleic acid in an amplification assay is from about 5 to about 30. In some examples, the number of amplification cycles for detecting a target nucleic acid is at least about 5. In some examples, the number of amplification cycles for detecting a target nucleic acid is at most about 30. In some examples, the number of amplification cycles for detecting a target nucleic acid is from about 5 to about 10, from about 5 to about 15, from about 5 to about 20, from about 5 to about 25, from about 5 to about 30, from about 10 to about 15, from about 10 to about 20, from about 10 to about 25, from about 10 to about 30, from about 15 to about 20, from about 15 to about 25, from about 15 to about 30, from about 20 to about 25, from about 20 to about 30, or from about 25 to about 30.

[0098] In one aspect, the methods provided herein for determining the presence, absence, and / or amount of a nucleic acid sequence from a particular genotype include an amplification reaction such as qPCR. In an exemplary method, the genetic material is obtained from a sample of interest, such as a blood or serum sample. In certain embodiments where the nucleic acid is extracted, the nucleic acid is extracted using any technique that does not interfere with subsequent analysis. In one embodiment, this technique uses an alcohol precipitation reaction with ethanol, methanol, or isopropyl alcohol. In one embodiment, this technique uses phenol, chloroform, or any combination thereof. In one embodiment, this technique uses cesium chloride. In one embodiment, this technique uses sodium, potassium, ammonium acetate, or any other salt commonly used to precipitate DNA. In one embodiment, this technique utilizes a column or resin-based nucleic acid purification scheme such as those commonly commercially available. One non-limiting example thereof is the GenElute Bacterial Genomic DNA Kit available from Sigma Aldrich. In one embodiment, after extraction, the nucleic acid is stored in water, Tris buffer, or Tris-EDTA buffer before being analyzed. In an exemplary embodiment, this nucleic acid material is extracted in water. Optionally, the extraction does not include nucleic acid purification.

[0099] In an exemplary qPCR assay, the nucleic acid sample is combined with a target nucleic acid that may or may not be present in the sample, and primers and probes specific for the DNA polymerase. The amplification reaction is performed using a thermal cycler that heats and cools the sample for nucleic acid amplification, irradiates the sample at a specific wavelength to excite the fluorophore on the probe, and detects the emitted fluorescence. In the TaqMan™ method, the probe may be a hydrolyzable probe that includes a fluorophore and a quencher that are hydrolyzed by the DNA polymerase when hybridized to the target nucleic acid. Optionally, the presence of the target nucleic acid is determined when the number of amplification cycles reaching the threshold is less than 30, 29, 28, 27, 26, 25, 24, 23, 22, 21, or 20.

[0100] In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 1 that contain a non-reference allele at nucleotide position 501 within SEQ ID NO: 1. In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 1 that contain a "G" or "A" allele at nucleotide position 501 within SEQ ID NO: 1. In some embodiments, detection of at least 10 adjacent nucleic acid molecules that contain a "G" or "A" allele at nucleotide position 501 within SEQ ID NO: 1 is sufficient to detect the polymorphism at rs11897732.

[0101] In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 2 that contain a non-reference allele at nucleotide position 501 within SEQ ID NO: 2. In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 2 that contain an "A" or "G" allele at nucleotide position 501 within SEQ ID NO: 2. In some embodiments, detection of at least 10 adjacent nucleic acid molecules that contain an "A" or "G" allele at nucleotide position 501 within SEQ ID NO: 2 is sufficient to detect the polymorphism at rs6740739.

[0102] In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 3 that contain a non-reference allele at nucleotide position 501 within SEQ ID NO: 3. In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 3 that contain a "G" or "C" allele at nucleotide position 501 within SEQ ID NO: 3. In some embodiments, detection of at least 10 adjacent nucleic acid molecules that contain a "G" or "C" allele at nucleotide position 501 within SEQ ID NO: 3 is sufficient to detect the polymorphism at rs17796285.

[0103] In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 4, including a non-reference allele at nucleotide position 501 within SEQ ID NO: 4. In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 4, including a "C" or "A" allele at nucleotide position 501 within SEQ ID NO: 4. In some embodiments, the detection of at least 10 adjacent nucleic acid molecules including a "C" or "A" allele at nucleotide position 501 within SEQ ID NO: 4 is sufficient to detect a polymorphism at rs7935393.

[0104] In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 5, including a non-reference allele at nucleotide position 501 within SEQ ID NO: 5. In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 5, including a "G" or "A" allele at nucleotide position 501 within SEQ ID NO: 5. In some embodiments, the detection of at least 10 adjacent nucleic acid molecules including a "G" or "A" allele at nucleotide position 501 within SEQ ID NO: 5 is sufficient to detect a polymorphism at rs12934476.

[0105] In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 6, including a non-reference allele at nucleotide position 501 within SEQ ID NO: 6. In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 6, including an "A" or "C" allele at nucleotide position 501 within SEQ ID NO: 6. In some embodiments, the detection of at least 10 adjacent nucleic acid molecules including an "A" or "C" allele at nucleotide position 501 within SEQ ID NO: 6 is sufficient to detect a polymorphism at rs12457255.

[0106] In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 7 that contain a non-reference allele at nucleotide position 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 that contain an "A" or "T" allele at nucleotide position 501 within SEQ ID NO: 7. In some embodiments, detection of at least 10 contiguous nucleic acid molecules that contain an "A" or "T" allele at nucleotide position 501 within SEQ ID NO: 7 is sufficient to detect the polymorphism at rs2070557.

[0107] In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 8 that contain a non-reference allele at nucleotide position 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 that contain an "A" or "G" allele at nucleotide position 501 within SEQ ID NO: 8. In some embodiments, detection of at least 10 contiguous nucleic acid molecules that contain an "A" or "G" allele at nucleotide position 501 within SEQ ID NO: 8 is sufficient to detect the polymorphism at rs4246905.

[0108] In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 9 that contain a non-reference allele at nucleotide position 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 that contain an "A" or "G" allele at nucleotide position 501 within SEQ ID NO: 9. In some embodiments, detection of at least 10 contiguous nucleic acid molecules that contain an "A" or "G" allele at nucleotide position 501 within SEQ ID NO: 9 is sufficient to detect the polymorphism at rs10974900.

[0109] In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 10, including a non-reference allele at nucleotide position 501 within SEQ ID NO: 10. In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 10, including a "C" or "A" allele at nucleotide position 501 within SEQ ID NO: 10. In some embodiments, the detection of at least 10 adjacent nucleic acid molecules including a "C" or "A" allele at nucleotide position 501 within SEQ ID NO: 10 is sufficient to detect the polymorphism at rs12434976.

[0110] In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 11, including a non-reference allele at nucleotide position 501 within SEQ ID NO: 11. In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 11, including an "A" or "C" allele at nucleotide position 501 within SEQ ID NO: 11. In some embodiments, the detection of at least 10 adjacent nucleic acid molecules including an "A" or "C" allele at nucleotide position 501 within SEQ ID NO: 11 is sufficient to detect the polymorphism at rs16901748.

[0111] In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 12, including a non-reference allele at nucleotide position 501 within SEQ ID NO: 12. In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 12, including an "A" or "G" allele at nucleotide position 501 within SEQ ID NO: 12. In some embodiments, the detection of at least 10 adjacent nucleic acid molecules including an "A" or "G" allele at nucleotide position 501 within SEQ ID NO: 12 is sufficient to detect the polymorphism at rs2815844.

[0112] In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 13, including a non-reference allele at nucleotide position 501 within SEQ ID NO: 13. In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 13, including a "G" or "A" allele at nucleotide position 501 within SEQ ID NO: 13. In some embodiments, the detection of at least 10 adjacent nucleic acid molecules including a "G" or "A" allele at nucleotide position 501 within SEQ ID NO: 13 is sufficient to detect the polymorphism at rs889702.

[0113] In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 14, including a non-reference allele at nucleotide position 501 within SEQ ID NO: 14. In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 14, including a "C" or "A" allele at nucleotide position 501 within SEQ ID NO: 14. In some embodiments, the detection of at least 10 adjacent nucleic acid molecules including a "C" or "A" allele at nucleotide position 501 within SEQ ID NO: 14 is sufficient to detect the polymorphism at rs2409750.

[0114] In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 15, including a non-reference allele at nucleotide position 501 within SEQ ID NO: 15. In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 15, including an "A" or "G" allele at nucleotide position 501 within SEQ ID NO: 15. In some embodiments, the detection of at least 10 adjacent nucleic acid molecules including an "A" or "G" allele at nucleotide position 501 within SEQ ID NO: 15 is sufficient to detect the polymorphism at rs1541020.

[0115] In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 16 that contain a non-reference allele at nucleotide position 501 within SEQ ID NO: 16. In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 16 that contain a "t" or "A" allele at nucleotide position 501 within SEQ ID NO: 16. In some embodiments, detection of at least 10 adjacent nucleic acid molecules that contain a "T" or "A" allele at nucleotide position 501 within SEQ ID NO: 16 is sufficient to detect the polymorphism at rs4942248.

[0116] In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 17 that contain a non-reference allele at nucleotide position 501 within SEQ ID NO: 17. In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 17 that contain a "G" or "A" allele at nucleotide position 501 within SEQ ID NO: 17. In some embodiments, detection of at least 10 adjacent nucleic acid molecules that contain a "G" or "A" allele at nucleotide position 501 within SEQ ID NO: 17 is sufficient to detect the polymorphism at rs12934476.

[0117] In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 18 that contain a non-reference allele at nucleotide position 501 within SEQ ID NO: 18. In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 18 that contain an "A" or "C" allele at nucleotide position 501 within SEQ ID NO: 18. In some embodiments, detection of at least 10 adjacent nucleic acid molecules that contain an "A" or "C" allele at nucleotide position 501 within SEQ ID NO: 18 is sufficient to detect the polymorphism at rs12457255.

[0118] In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 19, including a non-reference allele at nucleotide position 501 within SEQ ID NO: 19. In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 19, including an "A" or "G" allele at nucleotide position 501 within SEQ ID NO: 19. In some embodiments, the detection of at least 10 adjacent nucleic acid molecules including an "A" or "G" allele at nucleotide position 501 within SEQ ID NO: 19 is sufficient to detect a polymorphism at rs2297437.

[0119] In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 20, including a non-reference allele at nucleotide position 501 within SEQ ID NO: 20. In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 20, including a "G" or "A" allele at nucleotide position 501 within SEQ ID NO: 20. In some embodiments, the detection of at least 10 adjacent nucleic acid molecules including a "G" or "A" allele at nucleotide position 501 within SEQ ID NO: 20 is sufficient to detect a polymorphism at rs41309367.

[0120] In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 21, including a non-reference allele at nucleotide position 501 within SEQ ID NO: 21. In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 21, including an "A" or "G" allele at nucleotide position 501 within SEQ ID NO: 21. In some embodiments, the detection of at least 10 adjacent nucleic acid molecules including an "A" or "G" allele at nucleotide position 501 within SEQ ID NO: 21 is sufficient to detect a polymorphism at rs10733509.

[0121] In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 22 that contain a non-reference allele at nucleotide position 501 within SEQ ID NO: 22. In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 22 that contain a "G" or "A" allele at nucleotide position 501 within SEQ ID NO: 22. In some embodiments, detection of at least 10 adjacent nucleic acid molecules that contain a "G" or "A" allele at nucleotide position 501 within SEQ ID NO: 22 is sufficient to detect the polymorphism at rs10750376.

[0122] In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 23 that contain a non-reference allele at nucleotide position 501 within SEQ ID NO: 23. In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 23 that contain a "G" or "A" allele at nucleotide position 501 within SEQ ID NO: 23. In some embodiments, detection of at least 10 adjacent nucleic acid molecules that contain a "G" or "A" allele at nucleotide position 501 within SEQ ID NO: 23 is sufficient to detect the polymorphism at rs10932456.

[0123] In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 24 that contain a non-reference allele at nucleotide position 501 within SEQ ID NO: 24. In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 24 that contain an "A" or "G" allele at nucleotide position 501 within SEQ ID NO: 24. In some embodiments, detection of at least 10 adjacent nucleic acid molecules that contain an "A" or "G" allele at nucleotide position 501 within SEQ ID NO: 24 is sufficient to detect the polymorphism at rs1326860.

[0124] In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 25, including the "G" or "A" allele at nucleotide position 501 within SEQ ID NO: 25. In some embodiments, detection of at least 10 adjacent nucleic acid molecules including the "G" or "A" allele at nucleotide position 501 within SEQ ID NO: 25 is sufficient to detect the polymorphism at rs1528663.

[0125] In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 26, including the non-reference allele at nucleotide position 501 within SEQ ID NO: 26. In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 26, including the "C" or "A" allele at nucleotide position 501 within SEQ ID NO: 26. In some embodiments, detection of at least 10 adjacent nucleic acid molecules including the "C" or "A" allele at nucleotide position 501 within SEQ ID NO: 26 is sufficient to detect the polymorphism at rs1892231.

[0126] In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 27, including the non-reference allele at nucleotide position 501 within SEQ ID NO: 27. In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 27, including the "G" or "A" allele at nucleotide position 501 within SEQ ID NO: 27. In some embodiments, detection of at least 10 adjacent nucleic acid molecules including the "G" or "A" allele at nucleotide position 501 within SEQ ID NO: 27 is sufficient to detect the polymorphism at rs951279.

[0127] In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 28 that contain a non-reference allele at nucleotide position 501 within SEQ ID NO: 28. In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 28 that contain an "A" or "G" allele at nucleotide position 501 within SEQ ID NO: 28. In some embodiments, detection of at least 10 adjacent nucleic acid molecules that contain an "A" or "G" allele at nucleotide position 501 within SEQ ID NO: 28 is sufficient to detect a polymorphism at rs9806914.

[0128] In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 29 that contain a non-reference allele at nucleotide position 501 within SEQ ID NO: 29. In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 29 that contain a "C" or "A" allele at nucleotide position 501 within SEQ ID NO: 29. In some embodiments, detection of at least 10 adjacent nucleic acid molecules that contain a "C" or "A" allele at nucleotide position 501 within SEQ ID NO: 29 is sufficient to detect a polymorphism at rs7935393.

[0129] In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 30 that contain a non-reference allele at nucleotide position 501 within SEQ ID NO: 30. In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 30 that contain a "G" or "C" allele at nucleotide position 501 within SEQ ID NO: 30. In some embodiments, detection of at least 10 adjacent nucleic acid molecules that contain a "G" or "C" allele at nucleotide position 501 within SEQ ID NO: 30 is sufficient to detect a polymorphism at rs1690492.

[0130] In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 31 that contain a non-reference allele at nucleotide position 501 within SEQ ID NO: 31. In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 31 that contain a "G" or "A" allele at nucleotide position 501 within SEQ ID NO: 31. In some embodiments, the detection of at least 10 adjacent nucleic acid molecules that contain a "G" or "A" allele at nucleotide position 501 within SEQ ID NO: 31 is sufficient to detect a polymorphism at rs420726.

[0131] In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 32 that contain a non-reference allele at nucleotide position 501 within SEQ ID NO: 32. In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 32 that contain a "T" or "A" allele at nucleotide position 501 within SEQ ID NO: 32. In some embodiments, the detection of at least 10 adjacent nucleic acid molecules that contain a "T" or "A" allele at nucleotide position 501 within SEQ ID NO: 32 is sufficient to detect a polymorphism at rs7759385.

[0132] In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 33 that contain a non-reference allele at nucleotide position 501 within SEQ ID NO: 33. In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 33 that contain an "A" or "G" allele at nucleotide position 501 within SEQ ID NO: 33. In some embodiments, the detection of at least 10 adjacent nucleic acid molecules that contain an "A" or "G" allele at nucleotide position 501 within SEQ ID NO: 33 is sufficient to detect a polymorphism at rs10974900.

[0133] In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 34, including a non-reference allele at nucleotide position 501 within SEQ ID NO: 34. In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 34, including an "A" or "G" allele at nucleotide position 501 within SEQ ID NO: 34. In some embodiments, detection of at least 10 adjacent nucleic acid molecules including an "A" or "G" allele at nucleotide position 501 within SEQ ID NO: 34 is sufficient to detect a polymorphism at rs1326860.

[0134] In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 35, including a non-reference allele at nucleotide position 501 within SEQ ID NO: 35. In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 35, including a "C" or "G" allele at nucleotide position 501 within SEQ ID NO: 35. In some embodiments, detection of at least 10 adjacent nucleic acid molecules including a "C" or "G" allele at nucleotide position 501 within SEQ ID NO: 35 is sufficient to detect a polymorphism at rs2548147.

[0135] In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 36, including a non-reference allele at nucleotide position 501 within SEQ ID NO: 36. In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 36, including an "A" or "G" allele at nucleotide position 501 within SEQ ID NO: 36. In some embodiments, detection of at least 10 adjacent nucleic acid molecules including an "A" or "G" allele at nucleotide position 501 within SEQ ID NO: 36 is sufficient to detect a polymorphism at rs2815844.

[0136] In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 37, including a non-reference allele at nucleotide position 501 within SEQ ID NO: 37. In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 37, including a "G" or "A" allele at nucleotide position 501 within SEQ ID NO: 37. In some embodiments, detection of at least 10 adjacent nucleic acid molecules including a "G" or "A" allele at nucleotide position 501 within SEQ ID NO: 37 is sufficient to detect a polymorphism at rs889702.

[0137] In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 38, including a non-reference allele at nucleotide position 501 within SEQ ID NO: 38. In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 38, including an "A" or "G" allele at nucleotide position 501 within SEQ ID NO: 38. In some embodiments, detection of at least 10 adjacent nucleic acid molecules including an "A" or "G" allele at nucleotide position 501 within SEQ ID NO: 38 is sufficient to detect a polymorphism at rs9806914.

[0138] In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 39, including a non-reference allele at nucleotide position 501 within SEQ ID NO: 39. In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 39, including an "A" or "G" allele at nucleotide position 501 within SEQ ID NO: 39. In some embodiments, detection of at least 10 adjacent nucleic acid molecules including an "A" or "G" allele at nucleotide position 501 within SEQ ID NO: 39 is sufficient to detect a polymorphism at rs6478109.

[0139] In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 40 that contain a non-reference allele at nucleotide position 501 within SEQ ID NO: 40. In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 40 that contain a "C" or "G" allele at nucleotide position 501 within SEQ ID NO: 40. In some embodiments, detection of at least 10 adjacent nucleic acid molecules that contain a "C" or "G" allele at nucleotide position 501 within SEQ ID NO: 40 is sufficient to detect a polymorphism at rs7278257.

[0140] In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 41 that contain a non-reference allele at nucleotide position 501 within SEQ ID NO: 41. In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 41 that contain an "A" or "G" allele at nucleotide position 501 within SEQ ID NO: 41. In some embodiments, detection of at least 10 adjacent nucleic acid molecules that contain an "A" or "G" allele at nucleotide position 501 within SEQ ID NO: 41 is sufficient to detect a polymorphism at rs11221332.

[0141] In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 57 that contain a non-reference allele at nucleotide position 501 within SEQ ID NO: 57. In some embodiments, the target nucleic acid is at least 10 adjacent nucleic acid molecules of SEQ ID NO: 57 that contain an "A" or "G" allele at nucleotide position 501 within SEQ ID NO: 57. In some embodiments, detection of at least 10 adjacent nucleic acid molecules that contain an "A" or "G" allele at nucleotide position 501 within SEQ ID NO: 57 is sufficient to detect a polymorphism at rs56124762.

[0142] In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 58 that contain a non-reference allele at nucleotide position 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: 58 that contain an "A" or "G" allele at nucleotide position 501 within SEQ ID NO: 58. In some embodiments, detection of at least 10 contiguous nucleic acid molecules that contain an "A" or "G" allele at nucleotide position 501 within SEQ ID NO: 58 is sufficient to detect a polymorphism at rs2070558.

[0143] In some embodiments, the target nucleic acid is at least 10 contiguous nucleic acid molecules of SEQ ID NO: 59 that contain a non-reference allele at nucleotide position 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 that contain an "A" or "C" allele at nucleotide position 501 within SEQ ID NO: 59. In some embodiments, detection of at least 10 contiguous nucleic acid molecules that contain a "T" or "C" allele at nucleotide position 501 within SEQ ID NO: 59 is sufficient to detect a polymorphism at rs2070561.

[0144] In some embodiments, one target nucleic acid (e.g., a polymorphism) is detected by 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, at least 2, 3, 4, 5, 6, 7, 8, 9, or 10 target nucleic acids are detected in a single multiplex assay. In some embodiments, when 4 target nucleic acids are detected in a sample of interest, 4 unique 3-polymorphism combinations are measured. In a non-limiting example, a sample obtained from a subject (e.g., blood or plasma) is contacted with 4 primer pairs, each primer being suitable for amplifying rs6487109, rs56124762, rs1892231, and rs16901748, respectively. A positive, negative, or indeterminate TNFSF15 profile may be at least partially determined by which 3-polymorphism combinations are detected in the sample and / or whether the genotype is heterozygous or homozygous for the polymorphism. In this example, the analysis of 4 polymorphisms means that there may be a total of 4 unique 3-polymorphisms detected in the patient sample, which are rs6478109, rs56124762, rs1892231; rs6478109, rs56124762, rs16901748; rs6478109, rs1892231, rs16901748; and rs56124762, rs1892231, rs16901748. Each detected polymorphism may be heterozygous or homozygous.

[0145] To implement the methods and systems provided herein, genetic material can be extracted from a sample obtained from a subject, such as a blood or serum sample. In certain embodiments where nucleic acids are extracted, the nucleic acids are extracted using any technique that does not interfere with subsequent analysis. In one embodiment, this technique uses an alcohol precipitation reaction with ethanol, methanol, or isopropyl alcohol. In one embodiment, this technique uses phenol, chloroform, or any combination thereof. In one embodiment, this technique uses cesium chloride. In one embodiment, this technique uses sodium, potassium, ammonium acetate, or any other salt commonly used to precipitate DNA. In one embodiment, this technique utilizes a column or resin-based nucleic acid purification scheme, such as those commonly commercially available. One non-limiting example is the GenElute Bacterial Genomic DNA Kit available from Sigma Aldrich. In one embodiment, after extraction, the nucleic acids are stored in water, Tris buffer, or Tris-EDTA buffer and then analyzed. In an exemplary embodiment, this nucleic acid material is extracted in water. Optionally, the extraction does not include nucleic acid purification. In one embodiment, RNA can be extracted from cells using an RNA extraction technique that includes, for example, acid phenol / guanidinium isothiocyanate extraction (RNAzol B; Biogenesis), RNeasy RNA preparation kit (Qiagen), or PAXgene (PreAnalytix, Switzerland).

[0146] In some embodiments, a method of detecting the presence, absence, or level of a target protein (e.g., a biomarker) in a sample obtained from a subject includes a step of detecting protein activity or expression. In some embodiments, the target protein is TL1A, or a binding partner of TL1A such as decoy receptor 3 (DcR3). The target protein can be detected by use of an antibody-based assay, in which an antibody specific to the target protein is utilized. In some embodiments, the antibody-based detection method utilizes an antibody that binds to any region of the target protein. Exemplary assay methods include performing an enzyme-linked immunosorbent assay (ELISA). The ELISA assay may be a sandwich ELISA or a direct ELISA. Other exemplary assay methods include single molecule arrays, such as Simoa. Other exemplary detection methods include immunohistochemical examination and lateral flow assays. Further exemplary methods of detecting the target protein include 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), immunofluorescence assay, and Western blotting, but are not limited thereto. In some embodiments, an antibody or antibody fragment is used in methods such as Western blot or immunofluorescence to detect the expressed protein. The antibody or protein can be immobilized on a solid support for Western blot and immunofluorescence. Suitable solid phase supports or carriers include any support capable of binding an antigen or antibody. Exemplary supports or carriers include glass, polystyrene, polypropylene, polyethylene, dextran, nylon, amylases, natural and modified celluloses, polyacrylamide, slate, and magnetite.

[0147] In some cases, the target protein can be detected by detecting the binding of the target protein to its binding partner. Non-limiting examples of binding partners of TL1A include DcR3 and tumor necrosis factor receptor superfamily member 25 (TNR25). Exemplary methods for analyzing protein-protein binding include performing an assay in vivo, in vitro, or ex vivo. In some examples, the analysis methods include co-immunoprecipitation (co-IP), pull-down, cross-linking protein interaction analysis, labeled transfer protein interaction analysis, or far-western blot analysis, FRET-based assays such as FRET-FLIM, yeast two-hybrid assays (BiFC), or split luciferase assays.

[0148] This specification discloses a method for detecting the presence or level of one or more serological markers in a sample obtained from a subject. In some embodiments, the one or more serological markers include anti-Saccharomyces cerevisiae antibodies (ASCA), antineutrophil cytoplasmic antibodies (ANCA), antibodies against Escherichia coli outer membrane porin C (anti-OmpC), anti-chitin antibodies, pANCA antibodies, anti-I2 antibodies, and anti-Cbir1 flagellin antibodies. In some embodiments, the antibodies include immunoglobulin A (IgA), immunoglobulin G (IgG), immunoglobulin E (IgE), or immunoglobulin M (IgM), immunoglobulin D (IgD), or combinations thereof. Any suitable method for detecting the target proteins or biomarkers disclosed herein may be used to detect the presence, absence, or level of serological markers. In some embodiments, the presence or level of one or more serological markers is detected using enzyme-linked immunosorbent assay (ELISA), single molecule array (Simoa), immunohistochemical examination, 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. Fixed leukocyte or neutrophil ELISA may be useful for detecting certain serological markers such as those described in Saxon et al., 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 the positivity (e.g., blood positivity) of the presence or level of serological markers that reflects the ratio of the standard or reference value.In some embodiments, the standard value is obtained from and pooled serum from a well-characterized patient population reported as seroreactive to the serum marker of interest (e.g., patients diagnosed with or suspected of having the same disease or disorder). In some embodiments, the control or reference value includes 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100 EU. In some examples, the quartile sum score is calculated using, for example, the method reported by 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.

[0149] Treatment method Disclosed herein is a method of treating a disease or disorder of interest, or a symptom of a disease or disorder, the method comprising administering to the subject a therapeutically effective amount of one or more therapeutic agents. In some embodiments, the one or more therapeutic agents are administered to the subject alone (e.g., monotherapy). In some embodiments, the one or more therapeutic agents are administered in combination with additional agents. In some embodiments, the therapeutic agent is a first-line treatment for the disease or disorder. In some embodiments, the therapeutic agent is a second, third, or fourth-line treatment for the disease or disorder.

[0150] Therapeutic agent Aspects provided herein are methods of treating inflammatory, fibrostenotic, or fibrotic disorders or diseases by administering to a subject a therapeutically effective amount of an inhibitor of TNF superfamily member 15 (TL1A) activity or expression, provided that a genotype is detected in a sample obtained from the subject. Optionally, the TL1A protein comprises the amino acid sequence provided in any one of SEQ ID NOs: 50-52. Optionally, 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. The allosteric modulator of TL1A may indirectly affect TL1A on DR3, or TR6 / DcR3 on TL1A or DR3. The inhibitor of TL1A activity or expression may be a direct inhibitor or an indirect inhibitor. Non-limiting examples of inhibitors of TL1A expression include RNA-protein TL1A translation inhibitors, antisense oligonucleotides targeting TNFSF15 mRNA (such as miRNA or siRNA), and epigenome editing (targeting the DNA binding domain of TNFSF15, or post-translational modification of histone tails and / or DNA molecules). Non-limiting examples of inhibitors of TL1A activity include antagonists to the TL1A receptor (DR3 and TR6 / DcR3), antagonists to the TL1A antigen, and antagonists to gene expression products involved in TL1A-mediated diseases. Antagonists as described herein include, but are not limited to, anti-TL1A antibodies, anti-TL1A binding antibody fragments, or small molecules. The small molecule may be a small molecule that binds to TL1A or DR3. The anti-TL1A antibody may be a monoclonal antibody or a polyclonal antibody. The anti-TL1A antibody may be a humanized antibody or a chimeric antibody. The anti-TL1A antibody may be a fusion protein.The anti-TL1A antibody may be a blocking anti-TL1A antibody. A blocking antibody blocks the binding of two proteins, such as a ligand and its receptor. Therefore, a TL1A blocking antibody includes an antibody that prevents the binding of TL1A to the DR3 and / or TR6 / DcR3 receptor. In non-limiting examples, the TL1A blocking antibody binds to DR3. In another example, the TL1A blocking antibody binds to DcR3. Optionally, the TL1A antibody is an anti-TL1A antibody that specifically binds to TL1A. Optionally, the TL1A antibody specifically binds to an epitope of the TL1A protein provided in any one of SEQ ID NOs: 50-52. Optionally, the TL1A protein includes 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 include one or more of the antibody sequences in Table 2A or Table 2B. The anti-DR3 antibody may include 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 include an amino acid sequence that includes the HCDR1, HCDR2, HCDR3 domains of any one of SEQ ID NOs: 258-270 and the LCDR1, LCDR2, and LCDR3 of any one of SEQ ID NOs: 271-275.

[0151] In some embodiments, the anti-TL1A antibody includes a heavy chain that includes HCDR1, HCDR2, and HCDR3 as three complementarity determining regions, and a light chain that includes LCDR1, LCDR2, and LCDR3 as three complementarity determining regions. In some embodiments, the anti-TL1A antibody includes HCDR1 including SEQ ID NO: 109, HCDR2 including SEQ ID NO: 110, HCDR3 including SEQ ID NO: 111, LCDR1 including SEQ ID NO: 112, LCDR2 including SEQ ID NO: 113, and LCDR3 including SEQ ID NO: 114. Optionally, the anti-TL1A antibody includes a heavy chain (HC) variable domain including SEQ ID NO: 115 and a light chain (LC) variable domain including SEQ ID NO: 116.

[0152] In some embodiments, the anti-TL1A antibody comprises an HCDR1 comprising SEQ ID NO: 117, an HCDR2 comprising SEQ ID NO: 118, an HCDR3 comprising SEQ ID NO: 119, an LCDR1 comprising SEQ ID NO: 120, an LCDR2 comprising SEQ ID NO: 121, and an LCDR3 comprising SEQ ID NO: 122. Optionally, 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.

[0153] In some embodiments, the anti-TL1A antibody comprises an HCDR1 comprising SEQ ID NO: 125, an HCDR2 comprising SEQ ID NO: 126, an HCDR3 comprising SEQ ID NO: 127, an LCDR1 comprising SEQ ID NO: 128, an LCDR2 comprising SEQ ID NO: 129, and an LCDR3 comprising SEQ ID NO: 130. Optionally, 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.

[0154] In some embodiments, the anti-TL1A antibody comprises an HCDR1 comprising SEQ ID NO: 133, an HCDR2 comprising SEQ ID NO: 134, an HCDR3 comprising SEQ ID NO: 135, an LCDR1 comprising SEQ ID NO: 139, an LCDR2 comprising SEQ ID NO: 140, and an LCDR3 comprising SEQ ID NO: 141. In some embodiments, the anti-TL1A antibody comprises an HCDR1 comprising SEQ ID NO: 136, an HCDR2 comprising SEQ ID NO: 137, an HCDR3 comprising SEQ ID NO: 138, an LCDR1 comprising SEQ ID NO: 139, an LCDR2 comprising SEQ ID NO: 140, and an LCDR3 comprising SEQ ID NO: 141. Optionally, 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. Optionally, the anti-TL1A antibody comprises a heavy chain comprising SEQ ID NO: 144. Optionally, the anti-TL1A antibody comprises a light chain comprising SEQ ID NO: 145.

[0155] In some embodiments, the anti-TL1A antibody comprises an HCDR1 comprising SEQ ID NO: 146, an HCDR2 comprising SEQ ID NO: 147, an HCDR3 comprising SEQ ID NO: 148, an LCDR1 comprising SEQ ID NO: 149, an LCDR2 comprising SEQ ID NO: 150, and an LCDR3 comprising SEQ ID NO: 151. Optionally, 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.

[0156] In some embodiments, the anti-TL1A antibody comprises an HCDR1 comprising SEQ ID NO: 154, an HCDR2 comprising SEQ ID NO: 155, an HCDR3 comprising SEQ ID NO: 156, an LCDR1 comprising SEQ ID NO: 157, an LCDR2 comprising SEQ ID NO: 158, and an LCDR3 comprising SEQ ID NO: 159. Optionally, 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.

[0157] In some embodiments, the anti-TL1A antibody comprises an HCDR1 comprising SEQ ID NO: 162, an HCDR2 comprising SEQ ID NO: 164, an HCDR3 comprising SEQ ID NO: 165, an LCDR1 comprising SEQ ID NO: 167, an LCDR2 comprising SEQ ID NO: 169, and an LCDR3 comprising SEQ ID NO: 170. Optionally, 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. Optionally, 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. Optionally, 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. Optionally, 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.

[0158] In some embodiments, the anti-TL1A antibody comprises an HCDR1 comprising SEQ ID NO: 162, an HCDR2 comprising SEQ ID NO: 164, an HCDR3 comprising SEQ ID NO: 165, an LCDR1 comprising SEQ ID NO: 168, an LCDR2 comprising SEQ ID NO: 169, and an LCDR3 comprising SEQ ID NO: 170. Optionally, 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. Optionally, 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. Optionally, 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. Optionally, 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.

[0159] In some embodiments, the anti-TL1A antibody comprises an HCDR1 comprising SEQ ID NO: 162, an HCDR2 comprising SEQ ID NO: 164, an HCDR3 comprising SEQ ID NO: 165, an LCDR1 comprising SEQ ID NO: 167, an LCDR2 comprising SEQ ID NO: 169, and an LCDR3 comprising SEQ ID NO: 170. Optionally, 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. Optionally, 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. Optionally, 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. Optionally, 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.

[0160] In some embodiments, the anti-TL1A antibody comprises an HCDR1 comprising SEQ ID NO: 162, an HCDR2 comprising SEQ ID NO: 164, an HCDR3 comprising SEQ ID NO: 165, an LCDR1 comprising SEQ ID NO: 168, an LCDR2 comprising SEQ ID NO: 169, and an LCDR3 comprising SEQ ID NO: 170. Optionally, 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. Optionally, 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. Optionally, 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. Optionally, 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.

[0161] In some embodiments, the anti-TL1A antibody comprises an HCDR1 comprising SEQ ID NO: 163, an HCDR2 comprising SEQ ID NO: 164, an HCDR3 comprising SEQ ID NO: 166, an LCDR1 comprising SEQ ID NO: 167, an LCDR2 comprising SEQ ID NO: 169, and an LCDR3 comprising SEQ ID NO: 170. Optionally, 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. Optionally, 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. Optionally, 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. Optionally, 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. Optionally, 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. Optionally, 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. Optionally, 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. Optionally, 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.

[0162] In some embodiments, the anti-TL1A antibody comprises an HCDR1 comprising SEQ ID NO: 163, an HCDR2 comprising SEQ ID NO: 164, an HCDR3 comprising SEQ ID NO: 166, an LCDR1 comprising SEQ ID NO: 168, an LCDR2 comprising SEQ ID NO: 169, and an LCDR3 comprising SEQ ID NO: 170. Optionally, 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. Optionally, 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. Optionally, 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. Optionally, 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. Optionally, 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. Optionally, 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. Optionally, 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. Optionally, 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.

[0163] In some embodiments, the anti-TL1A antibody comprises an HCDR1 comprising SEQ ID NO: 183, an HCDR2 comprising SEQ ID NO: 184, an HCDR3 comprising SEQ ID NO: 185, an LCDR1 comprising SEQ ID NO: 186, an LCDR2 comprising SEQ ID NO: 187, and an LCDR3 comprising SEQ ID NO: 188. Optionally, 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. Optionally, 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. Optionally, 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. Optionally, 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. Optionally, 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. Optionally, 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. Optionally, 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. Optionally, 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. Optionally, 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. Optionally, 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. Optionally, 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. Optionally, 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.Optionally, 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. Optionally, 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. Optionally, 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. Optionally, 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. Optionally, 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. Optionally, 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. Optionally, 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. Optionally, 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.

[0164] In some embodiments, the anti-TL1A antibody comprises an HCDR1 comprising SEQ ID NO: 198, an HCDR2 comprising SEQ ID NO: 199, an HCDR3 comprising SEQ ID NO: 200, an LCDR1 comprising SEQ ID NO: 201, an LCDR2 comprising SEQ ID NO: 202, and an LCDR3 comprising SEQ ID NO: 203. Optionally, 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. Optionally, 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. Optionally, 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. Optionally, 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. Optionally, 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. Optionally, 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. Optionally, 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. Optionally, 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. Optionally, 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. Optionally, 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. Optionally, 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. Optionally, 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.

[0165] In some embodiments, the anti-TL1A antibody comprises an HCDR1 comprising SEQ ID NO: 228, an HCDR2 comprising SEQ ID NO: 229, an HCDR3 comprising SEQ ID NO: 230, an LCDR1 comprising SEQ ID NO: 231, an LCDR2 comprising SEQ ID NO: 232, and an LCDR3 comprising SEQ ID NO: 233. Optionally, 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.

[0166] In some embodiments, the anti-TL1A antibody comprises an HCDR1 comprising SEQ ID NO: 236, an HCDR2 comprising SEQ ID NO: 237, an HCDR3 comprising SEQ ID NO: 238, an LCDR1 comprising SEQ ID NO: 239, an LCDR2 comprising SEQ ID NO: 240, and an LCDR3 comprising SEQ ID NO: 241. Optionally, 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.

[0167] In some embodiments, the anti-TL1A antibody comprises an HCDR1 comprising SEQ ID NO: 246, an HCDR2 comprising SEQ ID NO: 247, an HCDR3 comprising SEQ ID NO: 248, an LCDR1 comprising SEQ ID NO: 249, an LCDR2 comprising SEQ ID NO: 250, and an LCDR3 comprising SEQ ID NO: 251. Optionally, 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. Optionally, 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. Optionally, 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. Optionally, 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.

[0168] In some embodiments, the anti-TL1A antibody comprises an HCDR1 comprising SEQ ID NO: 276, an HCDR2 comprising SEQ ID NO: 277, an HCDR3 comprising SEQ ID NO: 278, an LCDR1 comprising SEQ ID NO: 279, an LCDR2 comprising SEQ ID NO: 280, and an LCDR3 comprising SEQ ID NO: 281. Optionally, 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.

[0169] In some embodiments, the anti-TL1A antibody comprises an HCDR1 comprising SEQ ID NO: 284, an HCDR2 comprising SEQ ID NO: 285, an HCDR3 comprising SEQ ID NO: 286, an LCDR1 comprising SEQ ID NO: 287, an LCDR2 comprising SEQ ID NO: 288, and an LCDR3 comprising SEQ ID NO: 299. Optionally, 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.

[0170] 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.

[0171] 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.

[0172] Optionally, the anti-TL1A antibody binds to at least one of the same residues of human TL1A as the antibodies described herein. For example, the anti-TL1A antibody binds to at least one of the same residues of human TL1A as the antibody selected from A100 to A177. Optionally, the anti-TL1A antibody binds to the same epitope of human TL1A as the antibody selected from A100 to A177. Optionally, the anti-TL1A antibody binds to the same region of human TL1A as the antibody selected from A100 to A177.

[0173] In some embodiments, the anti-TL1A antibody comprises any one of the following Embodiments 1 to 547. 1. An antibody or antigen-binding fragment that specifically binds to TL1A, wherein the antibody or antigen-binding fragment is a heavy chain variable region comprising four heavy chain framework regions (HFR1, HFR2, HFR3, and HFR4) and three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), (a) (i) HFR1 comprising SEQ ID NO: 100100, (ii) HFR1 comprising SEQ ID NO: 100108, and (iii) HFR1 selected from HFR1s comprising an amino acid sequence that differs from the sequence consisting of SEQ ID NO: 100100 and 100108 by at most 5, 4, 3, or 2 amino acids, (b) (i) HFR2 comprising SEQ ID NO: 100101, and (ii) HFR2 selected from HFR2s comprising an amino acid sequence that differs from SEQ ID NO: 100100 by at most 5, 4, 3, or 2 amino acids, (c) (i) HFR3 comprising SEQ ID NO: 100102, (ii) HFR3 comprising SEQ ID NO: 100109, and (iii) HFR3 selected from HFR3s comprising an amino acid sequence that differs from the sequence consisting of SEQ ID NO: 100102 and 100109 by at most 5, 4, 3, or 2 amino acids, (d) (i) HFR4 comprising SEQ ID NO: 100103, and (ii) HFR4 selected from HFR4s comprising an amino acid sequence that differs from SEQ ID NO: 100103 by at most 5, 4, 3, or 2 amino acids, (e) (i) HCDR1 comprising SEQ ID NO: 1009, (ii) HCDR1 comprising SEQ ID NO: 100150 (wherein X1 is selected from D and E, X2 is selected from I, P, and ∨, X3 is selected from G, Q, S, and V, X4 is selected from F and Y, and X5 is selected from I and M), (iii) HCDR1 selected from SEQ ID NOs: 100200 - 100295, and (iv) HCDR1 selected from HCDR1s comprising an amino acid sequence that differs from the sequence consisting of SEQ ID NO: 1009, 100150, and 100200 - 100295 by at most 5, 4, 3, or 2 amino acids, (f) (i) An HCDR2 comprising SEQ ID NO: 10012, and (ii) an HCDR2 selected from HCDR2s comprising an amino acid sequence that differs from SEQ ID NO: 10012 by at most 5, 4, 3, or 2 amino acids, (g) (i) An HCDR3 comprising SEQ ID NO: 10015, (ii) an HCDR3 comprising SEQ ID NO: 100152 (wherein X1 is selected from L and M, and X2 is selected from E, I, K, L, M, Q, T, ∨, W, and Y), (iii) an HCDR3 selected from SEQ ID NOs: 100296 to 100314, and (iv) an HCDR3 selected from HCDR3s comprising an amino acid sequence that differs from a sequence selected from the group consisting of SEQ ID NOs: 10015, 100152, and 100296 to 100314 by at most 5, 4, 3, or 2 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), (a) (i) An LFR1 comprising SEQ ID NO: 100104, and (ii) an LFR1 selected from LFR1s comprising an amino acid sequence that differs from SEQ ID NO: 100104 by at most 5, 4, 3, or 2 amino acids, (b) (i) An LFR2 comprising SEQ ID NO: 100105, and (ii) an LFR2 selected from LFR2s comprising an amino acid sequence that differs from SEQ ID NO: 100105 by at most 5, 4, 3, or 2 amino acids, (c) (i) An LFR3 comprising SEQ ID NO: 100106, (ii) an LFR3 comprising SEQ ID NO: 100110, and (iii) an LFR3 selected from LFR3s comprising an amino acid sequence that differs from a sequence selected from the group consisting of SEQ ID NOs: 100106 and 100110 by at most 5, 4, 3, or 2 amino acids, (d) (i) An LFR4 comprising SEQ ID NO: 100107, and (ii) an LFR4 selected from LFR4s comprising an amino acid sequence that differs from SEQ ID NO: 100107 by at most 5, 4, 3, or 2 amino acids, (e) (i) an LCDR1 comprising SEQ ID NO: 10018, and (ii) an LCDR1 selected from LCDR1s comprising an amino acid sequence that differs from SEQ ID NO: 10018 by at most 5, 4, 3, or 2 amino acids (f) (i) an LCDR2 comprising SEQ ID NO: 10021, and (ii) an LCDR2 selected from LCDR2s comprising an amino acid sequence that differs from SEQ ID NO: 10021 by at most 5, 4, 3, or 2 amino acids (g) a light chain variable region comprising (i) an LCDR3 comprising SEQ ID NO: 10024, (ii) an LCDR3 comprising SEQ ID NO: 100155 (wherein X1 is selected from Q and N, X2 is selected from D, E, H, N, Q, and S, X3 is selected from A and G, and X4 is selected from D, F, K, N, R, S, and T), (iii) an LCDR3 selected from SEQ ID NOs: 100315 - 100482, and (iv) an LCDR3 selected from LCDR3s 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 at most 5, 4, 3, or 2 amino acids An antibody or antigen - binding fragment comprising the same. 2. The antibody or antigen - binding fragment according to embodiment 1, wherein HFR1 comprises SEQ ID NO: 100100. 3. The antibody or antigen - binding fragment according to embodiment 1, wherein HFR1 comprises SEQ ID NO: 100108. 4. The antibody or antigen - binding fragment according to embodiment 1, wherein HFR1 comprises an amino acid sequence that differs from SEQ ID NO: 100100 by at most 5, 4, 3, or 2 amino acids. 5. The antibody or antigen - binding fragment according to embodiment 1, wherein HFR1 comprises an amino acid sequence that differs from SEQ ID NO: 100108 by at most 5, 4, 3, or 2 amino acids. 6. The antibody or antigen - binding fragment according to any one of embodiments 1 to 5, wherein HFR2 comprises SEQ ID NO: 100101. 7. The antibody or antigen - binding fragment according to any one of embodiments 1 to 5, wherein HFR2 comprises an amino acid sequence that differs from SEQ ID NO: 100101 by at most 5, 4, 3, or 2 amino acids. 8. The antibody or antigen-binding fragment according to any one of embodiments 1 to 7, wherein HFR3 comprises SEQ ID NO: 100102. 9. The antibody or antigen-binding fragment according to any one of embodiments 1 to 7, wherein HFR3 comprises SEQ ID NO: 100109. 10. The antibody or antigen-binding fragment according to any one of embodiments 1 to 7, wherein HFR3 comprises an amino acid sequence that differs from SEQ ID NO: 100102 by at most 5, 4, 3, or 2 amino acids. 11. The antibody or antigen-binding fragment according to any one of embodiments 1 to 7, wherein HFR3 comprises an amino acid sequence that differs from SEQ ID NO: 100109 by at most 5, 4, 3, or 2 amino acids. 12. The antibody or antigen-binding fragment according to any one of embodiments 1 to 11, wherein HFR4 comprises SEQ ID NO: 100103. 13. The antibody or antigen-binding fragment according to any one of embodiments 1 to 11, wherein HFR4 comprises an amino acid sequence that differs from SEQ ID NO: 100103 by at most 5, 4, 3, or 2 amino acids. 14. The antibody or antigen-binding fragment according to any one of embodiments 1 to 13, wherein HCDR1 comprises SEQ ID NO: 1009. 15. The antibody or antigen-binding fragment according to any one of embodiments 1 to 13, wherein HCDR1 comprises SEQ ID NO: 100150. 16. The antibody or antigen-binding fragment according to embodiment 15, wherein X1 is E. 17. The antibody or antigen-binding fragment according to embodiment 15 or 16, wherein X2 is selected from P and V. 18. The antibody or antigen-binding fragment according to any one of embodiments 15 to 17, wherein X3 is selected from G, S, and V. 19. The antibody or antigen-binding fragment according to any one of embodiments 15 to 18, wherein X4 is F. 20. The antibody or antigen-binding fragment according to any one of embodiments 15 to 19, wherein X5 is I. 21. The antibody or antigen-binding fragment according to any one of embodiments 1 to 13, wherein HCDR1 comprises an amino acid sequence selected from SEQ ID NOs: 100200 to 100295. 22. The antibody or antigen-binding fragment according to any one of embodiments 1 to 21, wherein HCDR2 comprises SEQ ID NO: 10012. 23. The antibody or antigen-binding fragment according to any one of embodiments 1 to 21, wherein HCDR2 comprises an amino acid sequence that differs from SEQ ID NO: 10012 by at most 5, 4, 3, or 2 amino acids. 24. The antibody or antigen-binding fragment according to any one of embodiments 1 to 23, wherein HCDR3 comprises SEQ ID NO: 10015. 25. The antibody or antigen-binding fragment according to any one of embodiments 1 to 23, wherein HCDR3 comprises SEQ ID NO: 100152. 26. The antibody or antigen-binding fragment according to embodiment 25, wherein X1 is M. 27. The antibody or antigen-binding fragment according to embodiment 25 or 26, wherein X2 is selected from E, I, K, L, M, Q, T, W, and Y. 28. The antibody or antigen-binding fragment according to any one of embodiments 1 to 23, wherein HCDR3 comprises a sequence selected from SEQ ID NOs: 100296 to 100314. 29. The antibody or antigen-binding fragment according to any one of embodiments 1 to 28, wherein LFR1 comprises SEQ ID NO: 100104. 30. The antibody or antigen-binding fragment according to any one of embodiments 1 to 28, wherein LFR1 comprises an amino acid sequence that differs from SEQ ID NO: 100104 by at most 5, 4, 3, or 2 amino acids. 31. The antibody or antigen-binding fragment according to any one of embodiments 1 to 30, wherein LFR2 comprises SEQ ID NO: 100105. 32. The antibody or antigen-binding fragment according to any one of embodiments 1 to 30, wherein LFR2 comprises an amino acid sequence that differs from SEQ ID NO: 100105 by at most 5, 4, 3, or 2 amino acids. 33. An antibody or antigen-binding fragment according to any one of embodiments 1 to 32, wherein LFR3 comprises SEQ ID NO: 100106. 34. An antibody or antigen-binding fragment according to any one of embodiments 1 to 32, wherein LFR3 comprises SEQ ID NO: 100110. 35. An antibody or antigen-binding fragment according to any one of embodiments 1 to 32, wherein LFR3 comprises an amino acid sequence that differs from SEQ ID NO: 100106 by at most 5, 4, 3, or 2 amino acids. 36. An antibody or antigen-binding fragment according to any one of embodiments 1 to 32, wherein LFR3 comprises an amino acid sequence that differs from SEQ ID NO: 100110 by at most 5, 4, 3, or 2 amino acids. 37. An antibody or antigen-binding fragment according to any one of embodiments 1 to 36, wherein LFR4 comprises SEQ ID NO: 100107. 38. An antibody or antigen-binding fragment according to any one of embodiments 1 to 36, wherein LFR4 comprises an amino acid sequence that differs from SEQ ID NO: 100107 by at most 5, 4, 3, or 2 amino acids. 39. An antibody or antigen-binding fragment according to any one of embodiments 1 to 38, wherein LCDR1 comprises SEQ ID NO: 10018. 40. An antibody or antigen-binding fragment according to any one of embodiments 1 to 38, wherein LCDR1 comprises an amino acid sequence that differs from SEQ ID NO: 10018 by at most 5, 4, 3, or 2 amino acids. 41. An antibody or antigen-binding fragment according to any one of embodiments 1 to 40, wherein LCDR2 comprises SEQ ID NO: 10021. 42. An antibody or antigen-binding fragment according to any one of embodiments 1 to 40, wherein LCDR2 comprises an amino acid sequence that differs from SEQ ID NO: 10021 by at most 5, 4, 3, or 2 amino acids. 43. An antibody or antigen-binding fragment according to any one of embodiments 1 to 42, wherein LCDR3 comprises SEQ ID NO: 10024. 44. An antibody or antigen-binding fragment according to any one of embodiments 1 to 42, wherein LCDR3 comprises SEQ ID NO: 100155. The antibody or antigen-binding fragment according to embodiment 44, wherein X1 is N. The antibody or antigen-binding fragment according to embodiment 44 or 45, wherein X2 is selected from D, E, H, N, and Q. The antibody or antigen-binding fragment according to any one of embodiments 44 to 46, wherein X3 is A. The antibody or antigen-binding fragment according to any one of embodiments 44 to 47, wherein X4 is selected from D, F, K, R, S, and T. The antibody or antigen-binding fragment according to any one of embodiments 1 to 42, wherein LCDR3 comprises an amino acid sequence selected from SEQ ID NOs: 100315 to 100482. The antibody or antigen-binding fragment according to embodiment 1, wherein HFR1 comprises SEQ ID NO: 100100, HFR2 comprises SEQ ID NO: 100101, HFR3 comprises SEQ ID NO: 100102, HFR4 comprises SEQ ID NO: 100103, LFR1 comprises SEQ ID NO: 100104, LFR2 comprises SEQ ID NO: 100105, LFR3 comprises SEQ ID NO: 100106, and LFR4 comprises SEQ ID NO: 100107. The antibody or antigen-binding fragment according to embodiment 1, wherein HFR1 comprises SEQ ID NO: 100108, HFR2 comprises SEQ ID NO: 100101, HFR3 comprises SEQ ID NO: 100109, HFR4 comprises SEQ ID NO: 100103, LFR1 comprises SEQ ID NO: 100104, LFR2 comprises SEQ ID NO: 100105, LFR3 comprises SEQ ID NO: 100110, and LFR4 comprises SEQ ID NO: 100107. The antibody or antigen-binding fragment according to embodiment 1, wherein HFR1 comprises SEQ ID NO: 100108, HFR2 comprises SEQ ID NO: 100101, HFR3 comprises SEQ ID NO: 100109, HFR4 comprises SEQ ID NO: 100103, LFR1 comprises SEQ ID NO: 100104, LFR2 comprises SEQ ID NO: 100105, LFR3 comprises SEQ ID NO: 100106, and LFR4 comprises SEQ ID NO: 100107. An antibody or antigen-binding fragment according to any of embodiments 1 and 50 to 52, wherein HCDR1 comprises SEQ ID NO: 1009, HCDR2 comprises SEQ ID NO: 10012, HCDR3 comprises SEQ ID NO: 10015, LCDR1 comprises SEQ ID NO: 10018, LCDR2 comprises SEQ ID NO: 10021, and LCDR3 comprises SEQ ID NO: 10024. An antibody or antigen-binding fragment according to any of embodiments 1 and 50 to 52, wherein HCDR1 comprises SEQ ID NO: 100150, HCDR2 comprises SEQ ID NO: 10012, HCDR3 comprises SEQ ID NO: 100152, LCDR1 comprises SEQ ID NO: 10018, LCDR2 comprises SEQ ID NO: 10021, and LCDR3 comprises SEQ ID NO: 100155. An antibody or antigen-binding fragment according to embodiment 1, wherein HFR1 comprises SEQ ID NO: 100100, HFR2 comprises SEQ ID NO: 100101, HFR3 comprises SEQ ID NO: 100102, HFR4 comprises SEQ ID NO: 100103, LFR1 comprises SEQ ID NO: 100104, LFR2 comprises SEQ ID NO: 100105, LFR3 comprises SEQ ID NO: 100106, LFR4 comprises SEQ ID NO: 100107, HCDR1 comprises SEQ ID NO: 1009, HCDR2 comprises SEQ ID NO: 10012, HCDR3 comprises SEQ ID NO: 10015, LCDR1 comprises SEQ ID NO: 10018, LCDR2 comprises SEQ ID NO: 10021, and LCDR3 comprises SEQ ID NO: 10024. An antibody or antigen-binding fragment according to embodiment 1, wherein HFR1 comprises SEQ ID NO: 100100, HFR2 comprises SEQ ID NO: 100101, HFR3 comprises SEQ ID NO: 100102, HFR4 comprises SEQ ID NO: 100103, LFR1 comprises SEQ ID NO: 100104, LFR2 comprises SEQ ID NO: 100105, LFR3 comprises SEQ ID NO: 100106, LFR4 comprises SEQ ID NO: 100107, HCDR1 comprises SEQ ID NO: 100150, HCDR2 comprises SEQ ID NO: 10012, HCDR3 comprises SEQ ID NO: 100152, LCDR1 comprises SEQ ID NO: 10018, LCDR2 comprises SEQ ID NO: 10021, and LCDR3 comprises SEQ ID NO: 100155. 57. The antibody or antigen-binding fragment according to Embodiment 1, wherein HFR1 contains SEQ ID NO: 100108, HFR2 contains SEQ ID NO: 100101, HFR3 contains SEQ ID NO: 100109, HFR4 contains SEQ ID NO: 100103, LFR1 contains SEQ ID NO: 100104, LFR2 contains SEQ ID NO: 100105, LFR3 contains SEQ ID NO: 100110, LFR4 contains SEQ ID NO: 100107, HCDR1 contains SEQ ID NO: 1009, HCDR2 contains SEQ ID NO: 10012, HCDR3 contains SEQ ID NO: 10015, LCDR1 contains SEQ ID NO: 10018, LCDR2 contains SEQ ID NO: 10021, and LCDR3 contains SEQ ID NO: 10024. 58. The antibody or antigen-binding fragment according to Embodiment 1, wherein HFR1 contains SEQ ID NO: 100108, HFR2 contains SEQ ID NO: 100101, HFR3 contains SEQ ID NO: 100109, HFR4 contains SEQ ID NO: 100103, LFR1 contains SEQ ID NO: 100104, LFR2 contains SEQ ID NO: 100105, LFR3 contains SEQ ID NO: 100110, LFR4 contains SEQ ID NO: 100107, HCDR1 contains SEQ ID NO: 100150, HCDR2 contains SEQ ID NO: 10012, HCDR3 contains SEQ ID NO: 100152, LCDR1 contains SEQ ID NO: 10018, LCDR2 contains SEQ ID NO: 10021, and LCDR3 contains SEQ ID NO: 100155. 59. The antibody or antigen-binding fragment according to Embodiment 1, wherein HFR1 contains SEQ ID NO: 100108, HFR2 contains SEQ ID NO: 100101, HFR3 contains SEQ ID NO: 100109, HFR4 contains SEQ ID NO: 100103, LFR1 contains SEQ ID NO: 100104, LFR2 contains SEQ ID NO: 100105, LFR3 contains SEQ ID NO: 100106, LFR4 contains SEQ ID NO: 100107, HCDR1 contains SEQ ID NO: 1009, HCDR2 contains SEQ ID NO: 10012, HCDR3 contains SEQ ID NO: 10015, LCDR1 contains SEQ ID NO: 10018, LCDR2 contains SEQ ID NO: 10021, and LCDR3 contains SEQ ID NO: 10024. 60. The antibody or antigen-binding fragment according to Embodiment 1, wherein HFR1 contains SEQ ID NO: 100108, HFR2 contains SEQ ID NO: 100101, HFR3 contains SEQ ID NO: 100109, HFR4 contains SEQ ID NO: 100103, LFR1 contains SEQ ID NO: 100104, LFR2 contains SEQ ID NO: 100105, LFR3 contains SEQ ID NO: 100106, LFR4 contains SEQ ID NO: 100107, HCDR1 contains SEQ ID NO: 100150, HCDR2 contains SEQ ID NO: 10012, HCDR3 contains SEQ ID NO: 100152, LCDR1 contains SEQ ID NO: 10018, LCDR2 contains SEQ ID NO: 10021, and LCDR3 contains SEQ ID NO: 100155. 61. The antibody or antigen-binding fragment according to any one of Embodiments 1, 54, 56, 58, and 60, wherein X1 of SEQ ID NO: 100150 is D. 62. The antibody or antigen-binding fragment according to any one of Embodiments 1, 54, 56, 58, and 60, wherein X1 of SEQ ID NO: 100150 is E. 63. The antibody or antigen-binding fragment according to any one of Embodiments 1, 54, 56, 58, and 60 to 62, wherein X2 of SEQ ID NO: 100150 is I. 64. The antibody or antigen-binding fragment according to any one of Embodiments 1, 54, 56, 58, and 60 to 62, wherein X2 of SEQ ID NO: 100150 is P. 65. The antibody or antigen-binding fragment according to any one of Embodiments 1, 54, 56, 58, and 60 to 62, wherein X2 of SEQ ID NO: 100150 is V. 66. The antibody or antigen-binding fragment according to any one of Embodiments 1, 54, 56, 58, and 60 to 65, wherein X3 of SEQ ID NO: 100150 is G. 67. The antibody or antigen-binding fragment according to any one of Embodiments 1, 54, 56, 58, and 60 to 65, wherein X3 of SEQ ID NO: 100150 is Q. 68. The antibody or antigen-binding fragment according to any one of Embodiments 1, 54, 56, 58, and 60 to 65, wherein X3 of SEQ ID NO: 100150 is S. 69. An antibody or antigen-binding fragment according to any one of embodiments 1, 54, 56, 58, and 60 to 65, wherein X3 of SEQ ID NO: 100150 is V. 70. An antibody or antigen-binding fragment according to any one of embodiments 1, 54, 56, 58, and 60 to 69, wherein X4 of SEQ ID NO: 100150 is F. 71. An antibody or antigen-binding fragment according to any one of embodiments 1, 54, 56, 58, and 60 to 69, wherein X4 of SEQ ID NO: 100150 is Y. 72. An antibody or antigen-binding fragment according to any one of embodiments 1, 54, 56, 58, and 60 to 71, wherein X5 of SEQ ID NO: 100150 is I. 73. An antibody or antigen-binding fragment according to any one of embodiments 1, 54, 56, 58, and 60 to 71, wherein X5 of SEQ ID NO: 100150 is M. 74. An antibody or antigen-binding fragment according to any one of embodiments 1, 54, 56, 58, and 60 to 73, wherein X1 of SEQ ID NO: 100152 is L. 75. An antibody or antigen-binding fragment according to any one of embodiments 1, 54, 56, 58, and 60 to 73, wherein X1 of SEQ ID NO: 100152 is M. 76. An antibody or antigen-binding fragment according to any one of embodiments 1, 54, 56, 58, and 60 to 75, wherein X2 of SEQ ID NO: 100152 is E. 77. An antibody or antigen-binding fragment according to any one of embodiments 1, 54, 56, 58, and 60 to 75, wherein X2 of SEQ ID NO: 100152 is I. 78. An antibody or antigen-binding fragment according to any one of embodiments 1, 54, 56, 58, and 60 to 75, wherein X2 of SEQ ID NO: 100152 is K. 79. An antibody or antigen-binding fragment according to any one of embodiments 1, 54, 56, 58, and 60 to 75, wherein X2 of SEQ ID NO: 100152 is L. 80. An antibody or antigen-binding fragment according to any one of embodiments 1, 54, 56, 58, and 60 to 75, wherein X2 of SEQ ID NO: 100152 is M. 81. An antibody or antigen-binding fragment according to any one of embodiments 1, 54, 56, 58, and 60 to 75, wherein X2 of SEQ ID NO: 100152 is Q. 82. An antibody or antigen-binding fragment according to any one of embodiments 1, 54, 56, 58, and 60 to 75, wherein X2 of SEQ ID NO: 100152 is T. 83. An antibody or antigen-binding fragment according to any one of embodiments 1, 54, 56, 58, and 60 to 75, wherein X2 of SEQ ID NO: 100152 is V. 84. An antibody or antigen-binding fragment according to any one of embodiments 1, 54, 56, 58, and 60 to 75, wherein X2 of SEQ ID NO: 100152 is W. 85. An antibody or antigen-binding fragment according to any one of embodiments 1, 54, 56, 58, and 60 to 75, wherein X2 of SEQ ID NO: 100152 is Y. 86. An antibody or antigen-binding fragment according to any one of embodiments 1, 54, 56, 58, and 60 to 85, wherein X1 of SEQ ID NO: 100155 is Q. 87. An antibody or antigen-binding fragment according to any one of embodiments 1, 54, 56, 58, and 60 to 85, wherein X1 of SEQ ID NO: 100155 is N. 88. An antibody or antigen-binding fragment according to any one of embodiments 1, 54, 56, 58, and 60 to 87, wherein X2 of SEQ ID NO: 100155 is D. 89. An antibody or antigen-binding fragment according to any one of embodiments 1, 54, 56, 58, and 60 to 87, wherein X2 of SEQ ID NO: 100155 is E. 90. An antibody or antigen-binding fragment according to any one of embodiments 1, 54, 56, 58, and 60 to 87, wherein X2 of SEQ ID NO: 100155 is H. 91. An antibody or antigen-binding fragment according to any one of embodiments 1, 54, 56, 58, and 60 to 87, wherein X2 of SEQ ID NO: 100155 is N. 92. An antibody or antigen-binding fragment according to any one of embodiments 1, 54, 56, 58, and 60 to 87, wherein X2 of SEQ ID NO: 100155 is Q. 93. An antibody or antigen-binding fragment according to any one of embodiments 1, 54, 56, 58, and 60 to 87, wherein X2 of SEQ ID NO: 100155 is S. 94. An antibody or antigen-binding fragment according to any one of embodiments 1, 54, 56, 58, and 60 to 93, wherein X3 of SEQ ID NO: 100155 is A. 95. An antibody or antigen-binding fragment according to any one of embodiments 1, 54, 56, 58, and 60 to 93, wherein X3 of SEQ ID NO: 100155 is G. 96. An antibody or antigen-binding fragment according to any one of embodiments 1, 54, 56, 58, and 60 to 95, wherein X4 of SEQ ID NO: 100155 is D. 97. An antibody or antigen-binding fragment according to any one of embodiments 1, 54, 56, 58, and 60 to 95, wherein X4 of SEQ ID NO: 100155 is F. 98. An antibody or antigen-binding fragment according to any one of embodiments 1, 54, 56, 58, and 60 to 95, wherein X4 of SEQ ID NO: 100155 is K. 99. An antibody or antigen-binding fragment according to any one of embodiments 1, 54, 56, 58, and 60 to 95, wherein X4 of SEQ ID NO: 100155 is N. 100. An antibody or antigen-binding fragment according to any one of embodiments 1, 54, 56, 58, and 60 to 95, wherein X4 of SEQ ID NO: 100155 is R. 101. An antibody or antigen-binding fragment according to any one of embodiments 1, 54, 56, 58, and 60 to 95, wherein X4 of SEQ ID NO: 100155 is S. 102. An antibody or antigen-binding fragment according to any one of embodiments 1, 54, 56, 58, and 60 to 95, wherein X4 of SEQ ID NO: 100155 is T. 103. An antibody or antigen-binding fragment according to any one of embodiments 1 to 102, which specifically binds to human TL1A. 104.1x10 -9 K of M d The antibody or antigen-binding fragment according to embodiment 103 that specifically binds to human TL1A. 105.K d The antibody or antigen-binding fragment according to embodiment 104, wherein K is measured using a method selected from a standard ELISA assay and SPR. 106. The antibody or antigen-binding fragment according to any one of embodiments 1 to 105 that inhibits the binding of DR3 to human TL1A. 107. The antibody or antigen-binding fragment according to any one of embodiments 1 to 106 that inhibits the binding of DcR3 to human TL1A. 108. The antibody or antigen-binding fragment according to any one of embodiments 1 to 107, which is a humanized antibody, a CDR-grafted antibody, a chimeric antibody, a Fab, an ScFv, or a combination thereof. 109. The antibody or antigen-binding fragment according to any one of embodiments 1 to 108 that contains a human CH1 domain. 110. The antibody or antigen-binding fragment according to any one of embodiments 1 to 109 that contains a human CH2 domain. 111. The antibody or antigen-binding fragment according to embodiment 110, wherein the CH2 domain contains at least one mutation selected from L234A, L235A, and G237A, numbered as such using Kabat. 112. The antibody or antigen-binding fragment according to any one of embodiments 1 to 111 that contains a human CH3 domain. 113. A pharmaceutical composition comprising a therapeutically effective amount of the antibody or antigen-binding fragment according to any one of embodiments 1 to 112 and a pharmaceutically acceptable carrier. 114. A method for treating an inflammatory disease in a subject, the method comprising administering to the subject a therapeutically effective amount of the antibody or antigen-binding fragment according to any one of embodiments 1 to 113. 115. The method according to embodiment 114, wherein the inflammatory disease is an inflammatory bowel disease. 116. The method according to embodiment 115, wherein the inflammatory bowel disease includes Crohn's disease. 117. The method according to embodiment 116, wherein the subject is determined not to respond to anti-TNFα treatment. 118. The method according to embodiment 116 or 117, wherein the subject is determined to have a disease phenotype including non-stricturing / non-penetrating, stricturing, stricturing and penetrating, or isolated internal penetrating. 119. An antibody or antigen-binding fragment that specifically binds to TL1A, wherein the antibody or antigen-binding fragment is a heavy chain variable region comprising four heavy chain framework regions (HFR1, HFR2, HFR3, and HFR4) and three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) including SEQ ID NOs: 100100 to 100103, wherein the heavy chain complementarity determining regions (a) (i) HCDR1 comprising SEQ ID NO: 1009, (ii) HCDR1 comprising SEQ ID NO: 100150, wherein X1 is selected from D and E, X2 is selected from I, P, and V, X3 is selected from G, Q, S, and V, X4 is selected from F and Y, X5 is selected from I and M, (iii) HCDR1 selected from SEQ ID NOs: 100200 to 100295, and (iv) HCDR1 selected from HCDR1s comprising an amino acid sequence that differs from the sequences consisting of SEQ ID NO: 1009, 100150, and 100200 to 100295 by at most 5, 4, 3, or 2 amino acids; (b) (i) HCDR2 comprising SEQ ID NO: 10012, and (ii) HCDR2 selected from HCDR2s comprising an amino acid sequence that differs from SEQ ID NO: 10012 by at most 5, 4, 3, or 2 amino acids; (c) (i) An HCDR3 containing SEQ ID NO: 10015, (ii) an HCDR3 containing SEQ ID NO: 100152 (where X1 is selected from L and M, and X2 is selected from E, I, K, L, M, Q, T, ∨, W, and Y), (iii) an HCDR3 selected from SEQ ID NOs: 100296 to 100314, and (iv) an HCDR3 selected from an amino acid sequence that differs from the sequence selected from the group consisting of SEQ ID NOs: 10015, 100152, and 100296 to 100314 by at most 5, 4, 3, or 2 amino acids, and A light chain variable region comprising four light chain framework regions (LFR1, LFR2, LFR3, and LFR4) containing SEQ ID NOs: 100104 to 100107 and three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), wherein the light chain complementarity determining regions are (a) (i) An LCDR1 containing SEQ ID NO: 10018, and (ii) an LCDR1 selected from an amino acid sequence that differs from SEQ ID NO: 10018 by at most 5, 4, 3, or 2 amino acids, and (b) (i) An LCDR2 containing SEQ ID NO: 10021, and (ii) an LCDR2 selected from an amino acid sequence that differs from SEQ ID NO: 10021 by at most 5, 4, 3, or 2 amino acids, and (c) (i) An LCDR3 containing SEQ ID NO: 10024, (ii) an LCDR3 containing SEQ ID NO: 100155 (where X1 is selected from Q and N, X2 is selected from D, E, H, N, Q, and S, X3 is selected from A and G, and X4 is selected from D, F, K, N, R, S, and T), (iii) an LCDR3 selected from SEQ ID NOs: 100315 to 100482, and (iv) an LCDR3 selected from an amino acid sequence that differs from the sequence selected from the group consisting of SEQ ID NOs: 10024, 100155, and 100315 to 100482 by at most 5, 4, 3, or 2 amino acids, a light chain variable region An antibody or antigen-binding fragment comprising. 120. The antibody or antigen-binding fragment according to embodiment 119, wherein HCDR1 contains SEQ ID NO: 1009. 121. The antibody or antigen-binding fragment according to embodiment 119, wherein HCDR1 comprises SEQ ID NO: 100150. 122. The antibody or antigen-binding fragment according to embodiment 121, wherein X1 is E. 123. The antibody or antigen-binding fragment according to embodiment 121 or 122, wherein X2 is selected from P and V. 124. The antibody or antigen-binding fragment according to any one of embodiments 121 to 123, wherein X3 is selected from G, S, and V. 125. The antibody or antigen-binding fragment according to any one of embodiments 121 to 124, wherein X4 is F. 126. The antibody or antigen-binding fragment according to any one of embodiments 121 to 125, wherein X5 is I. 127. The antibody or antigen-binding fragment according to embodiment 119, wherein HCDR1 comprises an amino acid sequence selected from SEQ ID NOs: 100200 to 100295. 128. The antibody or antigen-binding fragment according to any one of embodiments 119 to 127, wherein HCDR2 comprises SEQ ID NO: 10012. 129. The antibody or antigen-binding fragment according to any one of embodiments 119 to 127, wherein HCDR2 comprises an amino acid sequence that differs from SEQ ID NO: 10012 by at most 5, 4, 3, or 2 amino acids. 130. The antibody or antigen-binding fragment according to any one of embodiments 119 to 129, wherein HCDR3 comprises SEQ ID NO: 10015. 131. The antibody or antigen-binding fragment according to any one of embodiments 119 to 129, wherein HCDR3 comprises SEQ ID NO: 100152. 132. The antibody or antigen-binding fragment according to embodiment 131, wherein X1 is M. 133. The antibody or antigen-binding fragment according to embodiment 131 or 132, wherein X2 is selected from E, I, K, L, M, Q, T, W, and Y. 134. The antibody or antigen-binding fragment according to any one of embodiments 119 to 129, wherein HCDR3 comprises a sequence selected from SEQ ID NOs: 100296 to 100314. 135. The antibody or antigen-binding fragment according to any one of embodiments 119 to 134, wherein LCDR1 comprises SEQ ID NO: 10018. 136. The antibody or antigen-binding fragment according to any one of embodiments 119 to 134, wherein LCDR1 comprises an amino acid sequence that differs from SEQ ID NO: 10018 by at most 5, 4, 3, or 2 amino acids. 137. The antibody or antigen-binding fragment according to any one of embodiments 119 to 136, wherein LCDR2 comprises SEQ ID NO: 10021. 138. The antibody or antigen-binding fragment according to any one of embodiments 119 to 136, wherein LCDR2 comprises an amino acid sequence that differs from SEQ ID NO: 10021 by at most 5, 4, 3, or 2 amino acids. 139. The antibody or antigen-binding fragment according to any one of embodiments 119 to 138, wherein LCDR3 comprises SEQ ID NO: 10024. 140. The antibody or antigen-binding fragment according to any one of embodiments 119 to 138, wherein LCDR3 comprises SEQ ID NO: 100155. 141. The antibody or antigen-binding fragment according to embodiment 140, wherein X1 is N. 142. The antibody or antigen-binding fragment according to embodiment 140 or 141, wherein X2 is selected from D, E, H, N, and Q. 143. The antibody or antigen-binding fragment according to any one of embodiments 140 to 142, wherein X3 is A. 144. The antibody or antigen-binding fragment according to any one of embodiments 140 to 143, wherein X4 is selected from D, F, K, R, S, and T. 145. The antibody or antigen-binding fragment according to any one of embodiments 119 to 138, wherein LCDR3 comprises an amino acid sequence selected from SEQ ID NOs: 100315 to 100482. 146. The antibody or antigen-binding fragment according to embodiment 119, wherein HCDR1 comprises SEQ ID NO: 1009, HCDR2 comprises SEQ ID NO: 10012, HCDR3 comprises SEQ ID NO: 10015, LCDR1 comprises SEQ ID NO: 10018, LCDR2 comprises SEQ ID NO: 10021, and LCDR3 comprises SEQ ID NO: 10024. 147. The antibody or antigen-binding fragment according to embodiment 119, wherein HCDR1 comprises SEQ ID NO: 100150, HCDR2 comprises SEQ ID NO: 10012, HCDR3 comprises SEQ ID NO: 100152, LCDR1 comprises SEQ ID NO: 10018, LCDR2 comprises SEQ ID NO: 10021, and LCDR3 comprises SEQ ID NO: 100155. 148. The antibody or antigen-binding fragment D according to embodiment 119 or 147, wherein X1 of SEQ ID NO: 100150 is D. 149. The antibody or antigen-binding fragment according to embodiment 119 or 147, wherein X1 of SEQ ID NO: 100150 is E. 150. The antibody or antigen-binding fragment according to any one of embodiments 119, 147 to 149, wherein X2 of SEQ ID NO: 100150 is I. 151. The antibody or antigen-binding fragment according to any one of embodiments 119, 147 to 149, wherein X2 of SEQ ID NO: 100150 is P. 152. The antibody or antigen-binding fragment according to any one of embodiments 119, 147 to 149, wherein X2 of SEQ ID NO: 100150 is V. 153. The antibody or antigen-binding fragment according to any one of embodiments 119, 147 to 152, wherein X3 of SEQ ID NO: 100150 is G. 154. The antibody or antigen-binding fragment according to any one of embodiments 119, 147 to 152, wherein X3 of SEQ ID NO: 100150 is Q. 155. The antibody or antigen-binding fragment according to any one of embodiments 119, 147 to 152, wherein X3 of SEQ ID NO: 100150 is S. 156. The antibody or antigen-binding fragment according to any one of embodiments 119, 147 to 152, wherein X3 of SEQ ID NO: 100150 is V. 157. The antibody or antigen-binding fragment according to any one of Embodiments 119 and 147 to 156, wherein X4 of SEQ ID NO: 100150 is F. 158. The antibody or antigen-binding fragment according to any one of Embodiments 119 and 147 to 156, wherein X4 of SEQ ID NO: 100150 is Y. 159. The antibody or antigen-binding fragment according to any one of Embodiments 119 and 147 to 158, wherein X5 of SEQ ID NO: 100150 is I. 160. The antibody or antigen-binding fragment according to any one of Embodiments 119 and 147 to 158, wherein X5 of SEQ ID NO: 100150 is M. 161. The antibody or antigen-binding fragment according to any one of Embodiments 119 and 147 to 160, wherein X1 of SEQ ID NO: 100152 is L. 162. The antibody or antigen-binding fragment according to any one of Embodiments 119 and 147 to 160, wherein X1 of SEQ ID NO: 100152 is M. 163. The antibody or antigen-binding fragment according to any one of Embodiments 119 and 147 to 162, wherein X2 of SEQ ID NO: 100152 is E. 164. The antibody or antigen-binding fragment according to any one of Embodiments 119 and 147 to 162, wherein X2 of SEQ ID NO: 100152 is I. 165. The antibody or antigen-binding fragment according to any one of Embodiments 119 and 147 to 162, wherein X2 of SEQ ID NO: 100152 is K. 166. The antibody or antigen-binding fragment according to any one of Embodiments 119 and 147 to 162, wherein X2 of SEQ ID NO: 100152 is L. 167. The antibody or antigen-binding fragment according to any one of Embodiments 119 and 147 to 162, wherein X2 of SEQ ID NO: 100152 is M. 168. The antibody or antigen-binding fragment according to any one of Embodiments 119 and 147 to 162, wherein X2 of SEQ ID NO: 100152 is Q. 169. The antibody or antigen-binding fragment according to any one of Embodiments 119 and 147 to 162, wherein X2 of SEQ ID NO: 100152 is T. 170. The antibody or antigen-binding fragment according to any one of Embodiments 119, 147 to 162, wherein X2 of SEQ ID NO: 100152 is V. 171. The antibody or antigen-binding fragment according to any one of Embodiments 119, 147 to 162, wherein X2 of SEQ ID NO: 100152 is W. 172. The antibody or antigen-binding fragment according to any one of Embodiments 119, 147 to 162, wherein X2 of SEQ ID NO: 100152 is Y. 173. The antibody or antigen-binding fragment according to any one of Embodiments 119, 147 to 172, wherein X1 of SEQ ID NO: 100155 is Q. 174. The antibody or antigen-binding fragment according to any one of Embodiments 119, 147 to 172, wherein X1 of SEQ ID NO: 100155 is N. 175. The antibody or antigen-binding fragment according to any one of Embodiments 119, 147 to 174, wherein X2 of SEQ ID NO: 100155 is D. 176. The antibody or antigen-binding fragment according to any one of Embodiments 119, 147 to 174, wherein X2 of SEQ ID NO: 100155 is E. 177. The antibody or antigen-binding fragment according to any one of Embodiments 119, 147 to 174, wherein X2 of SEQ ID NO: 100155 is H. 178. The antibody or antigen-binding fragment according to any one of Embodiments 119, 147 to 174, wherein X2 of SEQ ID NO: 100155 is N. 179. The antibody or antigen-binding fragment according to any one of Embodiments 119, 147 to 174, wherein X2 of SEQ ID NO: 100155 is Q. 180. The antibody or antigen-binding fragment according to any one of Embodiments 119, 147 to 174, wherein X2 of SEQ ID NO: 100155 is S. 181. The antibody or antigen-binding fragment according to any one of Embodiments 119, 147 to 180, wherein X3 of SEQ ID NO: 100155 is A. 182. The antibody or antigen-binding fragment according to any one of Embodiments 119, 147 to 180, wherein X3 of SEQ ID NO: 100155 is G. 183. The antibody or antigen-binding fragment according to any one of embodiments 119, 147 to 182, wherein X4 of SEQ ID NO: 100155 is D. 184. The antibody or antigen-binding fragment according to any one of embodiments 119, 147 to 182, wherein X4 of SEQ ID NO: 100155 is F. 185. The antibody or antigen-binding fragment according to any one of embodiments 119, 147 to 182, wherein X4 of SEQ ID NO: 100155 is K. 186. The antibody or antigen-binding fragment according to any one of embodiments 119, 147 to 182, wherein X4 of SEQ ID NO: 100155 is N. 187. The antibody or antigen-binding fragment according to any one of embodiments 119, 147 to 182, wherein X4 of SEQ ID NO: 100155 is R. 188. The antibody or antigen-binding fragment according to any one of embodiments 119, 147 to 182, wherein X4 of SEQ ID NO: 100155 is S. 189. The antibody or antigen-binding fragment according to any one of embodiments 119, 147 to 182, wherein X4 of SEQ ID NO: 100155 is T. 190. The antibody or antigen-binding fragment according to any one of embodiments 119 to 189, which specifically binds to human TL1A. 191. 1x10 -9 M of K d The antibody or antigen-binding fragment according to embodiment 190, which specifically binds to human TL1A at 1x10 192. K d The antibody or antigen-binding fragment according to embodiment 191, wherein K is measured using a method selected from standard ELISA assay and SPR. 193. The antibody or antigen-binding fragment according to any one of embodiments 119 to 192, which inhibits the binding of DR3 to human TL1A. 194. The antibody or antigen-binding fragment according to any one of embodiments 119 to 193, which inhibits the binding of DcR3 to human TL1A. The antibody or antigen-binding fragment according to any one of embodiments 119 to 194, which is a humanized antibody, a CDR-grafted antibody, a chimeric antibody, a Fab, an ScFv, or a combination thereof. 196. The antibody or antigen-binding fragment according to any one of embodiments 119 to 195, which comprises a human CH1 domain. 197. The antibody or antigen-binding fragment according to any one of embodiments 119 to 196, which comprises a human CH2 domain. 198. The antibody or antigen-binding fragment according to embodiment 197, wherein the CH2 domain comprises at least one mutation selected from L234A, L235A, and G237A, numbered using Kabat. 199. The antibody or antigen-binding fragment according to any one of embodiments 119 to 198, which comprises a human CH3 domain. 200. A pharmaceutical composition comprising a therapeutically effective amount of the antibody or antigen-binding fragment according to any one of embodiments 119 to 199 and a pharmaceutically acceptable carrier. 201. A method of treating an inflammatory disease in a subject, the method comprising administering to the subject a therapeutically effective amount of the antibody or antigen-binding fragment according to any one of embodiments 119 to 199. 202. The method according to embodiment 201, wherein the inflammatory disease is an inflammatory bowel disease. 203. The method according to embodiment 202, wherein the inflammatory bowel disease comprises Crohn's disease. 204. The method according to embodiment 203, wherein the subject has been determined to be non-responsive to anti-TNFα therapy. 205. The method according to embodiment 203 or 204, wherein the subject has been determined to have a disease phenotype comprising non-stricturing / non-penetrating, stricturing, stricturing, and penetrating, or isolated internal penetration. 206. An antibody or antigen-binding fragment that specifically binds to TL1A, wherein the antibody or antigen-binding fragment is A heavy chain variable region comprising four heavy chain framework regions (HFR1, HFR2, HFR3, and HFR4) and three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), each containing SEQ ID NO: 100108, 100101, 100109, and 100103, wherein the heavy chain complementarity determining regions are (a) (i) HCDR1 containing SEQ ID NO: 1009, (ii) HCDR1 containing SEQ ID NO: 100150 (where X1 is selected from D and E, X2 is selected from I, P, and V, X3 is selected from G, Q, S, and V, X4 is selected from F and Y, and X5 is selected from I and M), (iii) HCDR1 selected from SEQ ID NOs: 100200 - 100295, and (iv) HCDR1 selected from HCDR1s containing an amino acid sequence that differs from the sequences consisting of SEQ ID NO: 1009, 100150, and 100200 - 100295 by at most 5, 4, 3, or 2 amino acids (b) (i) HCDR2 containing SEQ ID NO: 10012, and (ii) HCDR2 selected from HCDR2s containing an amino acid sequence that differs from SEQ ID NO: 10012 by at most 5, 4, 3, or 2 amino acids (c) (i) HCDR3 containing SEQ ID NO: 10015, (ii) HCDR3 containing SEQ ID NO: 100152 (where X1 is selected from L and M, and X2 is selected from E, I, K, L, M, Q, T, V, W, and Y), (iii) HCDR3 selected from SEQ ID NOs: 100296 - 100314, and (iv) HCDR3 selected from HCDR3s containing an amino acid sequence that differs from the sequences consisting of SEQ ID NO: 10015, 100152, and 100296 - 100314 by at most 5, 4, 3, or 2 amino acids, a heavy chain variable region comprising 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), each containing SEQ ID NO: 100104, 100105, 100110, and 100107, wherein the light chain complementarity determining regions are (a) (i) An LCDR1 comprising SEQ ID NO: 10018, and (ii) an LCDR1 selected from LCDR1s comprising amino acid sequences that differ from SEQ ID NO: 10018 by at most 5, 4, 3, or 2 amino acids (b) (i) An LCDR2 comprising SEQ ID NO: 10021, and (ii) an LCDR2 selected from LCDR2s comprising amino acid sequences that differ from SEQ ID NO: 10021 by at most 5, 4, 3, or 2 amino acids (c) A light chain variable region comprising: (i) an LCDR3 comprising SEQ ID NO: 10024; (ii) an LCDR3 comprising SEQ ID NO: 100155, wherein X1 is selected from Q and N, X2 is selected from D, E, H, N, Q, and S, X3 is selected from A and G, and X4 is selected from D, F, K, N, R, S, and T; (iii) an LCDR3 selected from SEQ ID NOs: 100315 - 100482; and (iv) an LCDR3 selected from LCDR3s comprising amino acid sequences that differ from the sequences consisting of SEQ ID NOs: 10024, 100155, and 100315 - 100482 by at most 5, 4, 3, or 2 amino acids An antibody or antigen - binding fragment comprising the same 207. The antibody or antigen - binding fragment according to embodiment 206, wherein HCDR1 comprises SEQ ID NO: 1009. 208. The antibody or antigen - binding fragment according to embodiment 206, wherein HCDR1 comprises SEQ ID NO: 100150. 209. The antibody or antigen - binding fragment according to embodiment 208, wherein X1 is E. 210. The antibody or antigen - binding fragment according to embodiment 208 or 209, wherein X2 is selected from P and V. 211. The antibody or antigen - binding fragment according to any one of embodiments 208 - 210, wherein X3 is selected from G, S, and V. 212. The antibody or antigen - binding fragment according to any one of embodiments 208 - 211, wherein X4 is F. 213. The antibody or antigen - binding fragment according to any one of embodiments 208 - 212, wherein X5 is I. 214. The antibody or antigen-binding fragment according to embodiment 206, wherein HCDR1 comprises an amino acid sequence selected from SEQ ID NOs: 100200 to 100295. 215. The antibody or antigen-binding fragment according to any one of embodiments 206 to 214, wherein HCDR2 comprises SEQ ID NO: 10012. 216. The antibody or antigen-binding fragment according to any one of embodiments 206 to 214, wherein HCDR2 comprises an amino acid sequence that differs from SEQ ID NO: 10012 by at most 5, 4, 3, or 2 amino acids. 217. The antibody or antigen-binding fragment according to any one of embodiments 206 to 216, wherein HCDR3 comprises SEQ ID NO: 10015. 218. The antibody or antigen-binding fragment according to any one of embodiments 206 to 216, wherein HCDR3 comprises SEQ ID NO: 100152. 219. The antibody or antigen-binding fragment according to embodiment 218, wherein X1 is M. 220. The antibody or antigen-binding fragment according to embodiment 218 or 219, wherein X2 is selected from E, I, K, L, M, Q, T, W, and Y. 221. The antibody or antigen-binding fragment according to any one of embodiments 206 to 220, wherein HCDR3 comprises a sequence selected from SEQ ID NOs: 100296 to 100314. 222. The antibody or antigen-binding fragment according to any one of embodiments 206 to 221, wherein LCDR1 comprises SEQ ID NO: 10018. 223. The antibody or antigen-binding fragment according to any one of embodiments 206 to 221, wherein LCDR1 comprises an amino acid sequence that differs from SEQ ID NO: 10018 by at most 5, 4, 3, or 2 amino acids. 224. The antibody or antigen-binding fragment according to any one of embodiments 206 to 223, wherein LCDR2 comprises SEQ ID NO: 10021. 225. The antibody or antigen-binding fragment according to any one of embodiments 206 to 223, wherein LCDR2 comprises an amino acid sequence that differs from SEQ ID NO: 10021 by at most 5, 4, 3, or 2 amino acids. 226. An antibody or antigen-binding fragment according to any one of embodiments 206 to 225, wherein the LCDR3 comprises SEQ ID NO: 10024. 227. An antibody or antigen-binding fragment according to any one of embodiments 206 to 225, wherein the LCDR3 comprises SEQ ID NO: 100155. 228. An antibody or antigen-binding fragment according to embodiment 227, wherein X1 is N. 229. An antibody or antigen-binding fragment according to embodiment 227 or 228, wherein X2 is selected from D, E, H, N, and Q. 230. An antibody or antigen-binding fragment according to any one of embodiments 227 to 229, wherein X3 is A. 231. An antibody or antigen-binding fragment according to any one of embodiments 227 to 230, wherein X4 is selected from D, F, K, R, S, and T. 232. An antibody or antigen-binding fragment according to any one of embodiments 227 to 231, wherein the LCDR3 comprises an amino acid sequence selected from SEQ ID NOs: 100315 to 100482. 233. An antibody or antigen-binding fragment according to embodiment 206, wherein 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. An antibody or antigen-binding fragment according to embodiment 206, wherein 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. 235. An antibody or antigen-binding fragment D according to embodiment 206 or 234, wherein X1 of SEQ ID NO: 100150 is D. 236. An antibody or antigen-binding fragment according to embodiment 206 or 234, wherein X1 of SEQ ID NO: 100150 is E. The antibody or antigen-binding fragment according to any one of embodiments 206 and 234 to 236, wherein X2 of SEQ ID NO: 100150 is I. The antibody or antigen-binding fragment according to any one of embodiments 206 and 234 to 236, wherein X2 of SEQ ID NO: 100150 is P. The antibody or antigen-binding fragment according to any one of embodiments 206 and 234 to 236, wherein X2 of SEQ ID NO: 100150 is V. The antibody or antigen-binding fragment according to any one of embodiments 206 and 234 to 239, wherein X3 of SEQ ID NO: 100150 is G. The antibody or antigen-binding fragment according to any one of embodiments 206 and 234 to 239, wherein X3 of SEQ ID NO: 100150 is Q. The antibody or antigen-binding fragment according to any one of embodiments 206 and 234 to 239, wherein X3 of SEQ ID NO: 100150 is S. The antibody or antigen-binding fragment according to any one of embodiments 206 and 234 to 239, wherein X3 of SEQ ID NO: 100150 is V. The antibody or antigen-binding fragment according to any one of embodiments 206 and 234 to 243, wherein X4 of SEQ ID NO: 100150 is F. The antibody or antigen-binding fragment according to any one of embodiments 206 and 234 to 243, wherein X4 of SEQ ID NO: 100150 is Y. The antibody or antigen-binding fragment according to any one of embodiments 206 and 234 to 245, wherein X5 of SEQ ID NO: 100150 is I. The antibody or antigen-binding fragment according to any one of embodiments 206 and 234 to 245, wherein X5 of SEQ ID NO: 100150 is M. The antibody or antigen-binding fragment according to any one of embodiments 206 and 234 to 247, wherein X1 of SEQ ID NO: 100152 is L. The antibody or antigen-binding fragment according to any one of embodiments 206 and 234 to 247, wherein X1 of SEQ ID NO: 100152 is M. 250. The antibody or antigen-binding fragment according to any one of Embodiments 206, 234 to 249, wherein X2 of SEQ ID NO: 100152 is E. 251. The antibody or antigen-binding fragment according to any one of Embodiments 206, 234 to 249, wherein X2 of SEQ ID NO: 100152 is I. 252. The antibody or antigen-binding fragment according to any one of Embodiments 206, 234 to 249, wherein X2 of SEQ ID NO: 100152 is K. 253. The antibody or antigen-binding fragment according to any one of Embodiments 206, 234 to 249, wherein X2 of SEQ ID NO: 100152 is L. 254. The antibody or antigen-binding fragment according to any one of Embodiments 206, 234 to 249, wherein X2 of SEQ ID NO: 100152 is M. 255. The antibody or antigen-binding fragment according to any one of Embodiments 206, 234 to 249, wherein X2 of SEQ ID NO: 100152 is Q. 256. The antibody or antigen-binding fragment according to any one of Embodiments 206, 234 to 249, wherein X2 of SEQ ID NO: 100152 is T. 257. The antibody or antigen-binding fragment according to any one of Embodiments 206, 234 to 249, wherein X2 of SEQ ID NO: 100152 is V. 258. The antibody or antigen-binding fragment according to any one of Embodiments 206, 234 to 249, wherein X2 of SEQ ID NO: 100152 is W. 259. The antibody or antigen-binding fragment according to any one of Embodiments 206, 234 to 249, wherein X2 of SEQ ID NO: 100152 is Y. 260. The antibody or antigen-binding fragment according to any one of Embodiments 206, 234 to 259, wherein X1 of SEQ ID NO: 100155 is Q. 261. The antibody or antigen-binding fragment according to any one of Embodiments 206, 234 to 259, wherein X1 of SEQ ID NO: 100155 is N. 262. The antibody or antigen-binding fragment according to any one of Embodiments 206, 234 to 261, wherein X2 of SEQ ID NO: 100155 is D. 263. An antibody or antigen-binding fragment according to any one of embodiments 206 to 261, wherein X2 of SEQ ID NO: 100155 is E. 264. An antibody or antigen-binding fragment according to any one of embodiments 206 to 261, wherein X2 of SEQ ID NO: 100155 is H. 265. An antibody or antigen-binding fragment according to any one of embodiments 206 to 261, wherein X2 of SEQ ID NO: 100155 is N. 266. An antibody or antigen-binding fragment according to any one of embodiments 206 to 261, wherein X2 of SEQ ID NO: 100155 is Q. 267. An antibody or antigen-binding fragment according to any one of embodiments 206 to 261, wherein X2 of SEQ ID NO: 100155 is S. 268. An antibody or antigen-binding fragment according to any one of embodiments 206 to 267, wherein X3 of SEQ ID NO: 100155 is A. 269. An antibody or antigen-binding fragment according to any one of embodiments 206 to 267, wherein X3 of SEQ ID NO: 100155 is G. 270. An antibody or antigen-binding fragment according to any one of embodiments 206 to 269, wherein X4 of SEQ ID NO: 100155 is D. 271. An antibody or antigen-binding fragment according to any one of embodiments 206 to 269, wherein X4 of SEQ ID NO: 100155 is F. 272. An antibody or antigen-binding fragment according to any one of embodiments 206 to 269, wherein X4 of SEQ ID NO: 100155 is K. 273. An antibody or antigen-binding fragment according to any one of embodiments 206 to 269, wherein X4 of SEQ ID NO: 100155 is N. 274. An antibody or antigen-binding fragment according to any one of embodiments 206 to 269, wherein X4 of SEQ ID NO: 100155 is R. 275. An antibody or antigen-binding fragment according to any one of embodiments 206 to 269, wherein X4 of SEQ ID NO: 100155 is S. 276. An antibody or antigen-binding fragment according to any one of embodiments 206, 234 to 269, wherein X4 of SEQ ID NO: 100155 is T. 277. An antibody or antigen-binding fragment according to any one of embodiments 206 to 276, which specifically binds to human TL1A. 278. An antibody or antigen-binding fragment according to embodiment 277, which specifically binds to human TL1A at 1×10 -9 M of K d . 279. An antibody or antigen-binding fragment according to embodiment 278, wherein K d is measured using a method selected from standard ELISA assays and SPR. 280. An antibody or antigen-binding fragment according to any one of embodiments 206 to 279, which inhibits the binding of DR3 to human TL1A. 281. An antibody or antigen-binding fragment according to any one of embodiments 206 to 280, which inhibits the binding of DcR3 to human TL1A. 282. An antibody or antigen-binding fragment according to any one of embodiments 206 to 281, which is a humanized antibody, a CDR-grafted antibody, a chimeric antibody, a Fab, an ScFv, or a combination thereof. 283. An antibody or antigen-binding fragment according to any one of embodiments 206 to 282, which contains a human CH1 domain. 284. An antibody or antigen-binding fragment according to any one of embodiments 206 to 283, which contains a human CH2 domain. 285. An antibody or antigen-binding fragment according to embodiment 284, wherein the CH2 domain contains at least one mutation selected from L234A, L235A, and G237A, numbered using Kabat. 286. An antibody or antigen-binding fragment according to any one of embodiments 206 to 285, which contains a human CH3 domain. 287. A pharmaceutical composition comprising a therapeutically effective amount of an antibody or antigen-binding fragment according to any one of embodiments 206 to 286 and a pharmaceutically acceptable carrier. 288. A method of treating an inflammatory disease of interest, the method comprising administering to the subject a therapeutically effective amount of an antibody or antigen-binding fragment according to any one of embodiments 206 to 286. 289. The method of embodiment 288, wherein the inflammatory disease is an inflammatory bowel disease. 290. The method of embodiment 289, wherein the inflammatory bowel disease includes Crohn's disease. 291. The method of embodiment 290, wherein the subject has been determined not to respond to anti-TNFα therapy. 292. The method of embodiment 290 or 291, wherein the subject has been determined to have a disease phenotype including non-stricturing / non-penetrating, stricturing, stricturing and penetrating, or isolated internal penetration. 293. An antibody or antigen-binding fragment that specifically binds to TL1A, the antibody or antigen-binding fragment comprising a heavy chain variable region comprising four heavy chain framework regions (HFR1, HFR2, HFR3, and HFR4) each comprising SEQ ID NO: 100108, 100101, 100109, and 100103 and three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), wherein the heavy chain complementarity determining regions are (a) (i) HCDR1 comprising SEQ ID NO: 1009, (ii) HCDR1 comprising SEQ ID NO: 100150 (wherein X1 is selected from D and E, X2 is selected from I, P, and V, X3 is selected from G, Q, S, and V, X4 is selected from F and Y, and X5 is selected from I and M), (iii) HCDR1 selected from SEQ ID NOs: 100200 to 100295, and (iv) HCDR1 selected from HCDR1s comprising an amino acid sequence that differs from the sequences consisting of SEQ ID NOs: 1009, 100150, and 100200 to 100295 by at most 5, 4, 3, or 2 amino acids, (b) (i) HCDR2 comprising SEQ ID NO: 10012, and (ii) HCDR2 selected from HCDR2s comprising an amino acid sequence that differs from SEQ ID NO: 10012 by at most 5, 4, 3, or 2 amino acids, (c) (i) An HCDR3 containing SEQ ID NO: 10015, (ii) an HCDR3 containing SEQ ID NO: 100152 (where X1 is selected from L and M, and X2 is selected from E, I, K, L, M, Q, T, V, W, and Y), (iii) an HCDR3 selected from SEQ ID NOs: 100296 - 100314, and (iv) an HCDR3 selected from HCDRs containing an amino acid sequence that differs from the sequences selected from the group consisting of SEQ ID NO: 10015, 100152, and 100296 - 100314 by at most 5, 4, 3, or 2 amino acids, and A light chain variable region containing four light chain framework regions (LFR1, LFR2, LFR3, and LFR4) and three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3) containing SEQ ID NOs: 100104 - 100107, wherein the light chain complementarity determining regions are (a) (i) An LCDR1 containing SEQ ID NO: 10018, and (ii) an LCDR1 selected from LCDRs containing an amino acid sequence that differs from SEQ ID NO: 10018 by at most 5, 4, 3, or 2 amino acids, and (b) (i) An LCDR2 containing SEQ ID NO: 10021, and (ii) an LCDR2 selected from LCDRs containing an amino acid sequence that differs from SEQ ID NO: 10021 by at most 5, 4, 3, or 2 amino acids, and (c) (i) An LCDR3 containing SEQ ID NO: 10024, (ii) an LCDR3 containing SEQ ID NO: 100155 (where X1 is selected from Q and N, X2 is selected from D, E, H, N, Q, and S, X3 is selected from A and G, and X4 is selected from D, F, K, N, R, S, and T), (iii) an LCDR3 selected from SEQ ID NOs: 100315 - 100482, and (iv) an LCDR3 selected from LCDRs containing an amino acid sequence that differs from the sequences selected from the group consisting of SEQ ID NO: 10024, 100155, and 100315 - 100482 by at most 5, 4, 3, or 2 amino acids, a light chain variable region An antibody or antigen - binding fragment containing the same. 294. The antibody or antigen - binding fragment according to embodiment 293, wherein HCDR1 contains SEQ ID NO: 1009. The antibody or antigen-binding fragment according to embodiment 293, wherein HCDR1 comprises SEQ ID NO: 100150. The antibody or antigen-binding fragment according to embodiment 295, wherein X1 is E. The antibody or antigen-binding fragment according to embodiment 295 or 296, wherein X2 is selected from P and V. The antibody or antigen-binding fragment according to any one of embodiments 295 to 297, wherein X3 is selected from G, S, and V. The antibody or antigen-binding fragment according to any one of embodiments 295 to 298, wherein X4 is F. The antibody or antigen-binding fragment according to any one of embodiments 295 to 299, wherein X5 is I. The antibody or antigen-binding fragment according to embodiment 293, wherein HCDR1 comprises an amino acid sequence selected from SEQ ID NOs: 100200 to 100295. The antibody or antigen-binding fragment according to any one of embodiments 293 to 301, wherein HCDR2 comprises SEQ ID NO: 10012. The antibody or antigen-binding fragment according to any one of embodiments 293 to 301, wherein HCDR2 comprises an amino acid sequence that differs from SEQ ID NO: 10012 by at most 5, 4, 3, or 2 amino acids. The antibody or antigen-binding fragment according to any one of embodiments 293 to 303, wherein HCDR3 comprises SEQ ID NO: 10015. The antibody or antigen-binding fragment according to any one of embodiments 293 to 303, wherein HCDR3 comprises SEQ ID NO: 100152. The antibody or antigen-binding fragment according to embodiment 305, wherein X1 is M. The antibody or antigen-binding fragment according to embodiment 305 or 306, wherein X2 is selected from E, I, K, L, M, Q, T, W, and Y. The antibody or antigen-binding fragment according to any one of embodiments 293 to 303, wherein the HCDR3 comprises a sequence selected from SEQ ID NOs: 100296 to 100314. The antibody or antigen-binding fragment according to any one of embodiments 293 to 308, wherein the LCDR1 comprises SEQ ID NO: 10018. The antibody or antigen-binding fragment according to any one of embodiments 293 to 308, wherein the LCDR1 comprises an amino acid sequence that differs from SEQ ID NO: 10018 by at most 5, 4, 3, or 2 amino acids. The antibody or antigen-binding fragment according to any one of embodiments 293 to 310, wherein the LCDR2 comprises SEQ ID NO: 10021. The antibody or antigen-binding fragment according to any one of embodiments 293 to 310, wherein the LCDR2 comprises an amino acid sequence that differs from SEQ ID NO: 10021 by at most 5, 4, 3, or 2 amino acids. The antibody or antigen-binding fragment according to any one of embodiments 293 to 312, wherein the LCDR3 comprises SEQ ID NO: 10024. The antibody or antigen-binding fragment according to any one of embodiments 293 to 312, wherein the LCDR3 comprises SEQ ID NO: 100155. The antibody or antigen-binding fragment according to embodiment 314, wherein X1 is N. The antibody or antigen-binding fragment according to embodiment 314 or 315, wherein X2 is selected from D, E, H, N, and Q. The antibody or antigen-binding fragment according to any one of embodiments 314 to 316, wherein X3 is A. The antibody or antigen-binding fragment according to any one of embodiments 314 to 317, wherein X4 is selected from D, F, K, R, S, and T. The antibody or antigen-binding fragment according to any one of embodiments 314 to 312, wherein the LCDR3 comprises an amino acid sequence selected from SEQ ID NOs: 100315 to 100482. The antibody or antigen-binding fragment according to embodiment 293, wherein HCDR1 contains SEQ ID NO: 1009, HCDR2 contains SEQ ID NO: 10012, HCDR3 contains SEQ ID NO: 10015, LCDR1 contains SEQ ID NO: 10018, LCDR2 contains SEQ ID NO: 10021, and LCDR3 contains SEQ ID NO: 10024. The antibody or antigen-binding fragment according to embodiment 293, wherein HCDR1 contains SEQ ID NO: 100150, HCDR2 contains SEQ ID NO: 10012, HCDR3 contains SEQ ID NO: 100152, LCDR1 contains SEQ ID NO: 10018, LCDR2 contains SEQ ID NO: 10021, and LCDR3 contains SEQ ID NO: 100155. The antibody or antigen-binding fragment D according to embodiment 293 or 321, wherein X1 of SEQ ID NO: 100150 is D. The antibody or antigen-binding fragment according to embodiment 293 or 321, wherein X1 of SEQ ID NO: 100150 is E. The antibody or antigen-binding fragment according to any one of embodiments 293, 321 to 323, wherein X2 of SEQ ID NO: 100150 is I. The antibody or antigen-binding fragment according to any one of embodiments 293, 321 to 323, wherein X2 of SEQ ID NO: 100150 is P. The antibody or antigen-binding fragment according to any one of embodiments 293, 321 to 323, wherein X2 of SEQ ID NO: 100150 is V. The antibody or antigen-binding fragment according to any one of embodiments 293, 321 to 326, wherein X3 of SEQ ID NO: 100150 is G. The antibody or antigen-binding fragment according to any one of embodiments 293, 321 to 326, wherein X3 of SEQ ID NO: 100150 is Q. The antibody or antigen-binding fragment according to any one of embodiments 293, 321 to 326, wherein X3 of SEQ ID NO: 100150 is S. The antibody or antigen-binding fragment according to any one of embodiments 293, 321 to 326, wherein X3 of SEQ ID NO: 100150 is V. 331. The antibody or antigen-binding fragment according to any one of Embodiments 293 and 321 to 330, wherein X4 of SEQ ID NO: 100150 is F. 332. The antibody or antigen-binding fragment according to any one of Embodiments 293 and 321 to 330, wherein X4 of SEQ ID NO: 100150 is Y. 333. The antibody or antigen-binding fragment according to any one of Embodiments 293 and 321 to 332, wherein X5 of SEQ ID NO: 100150 is I. 334. The antibody or antigen-binding fragment according to any one of Embodiments 293 and 321 to 332, wherein X5 of SEQ ID NO: 100150 is M. 335. The antibody or antigen-binding fragment according to any one of Embodiments 293 and 321 to 334, wherein X1 of SEQ ID NO: 100152 is L. 336. The antibody or antigen-binding fragment according to any one of Embodiments 293 and 321 to 334, wherein X1 of SEQ ID NO: 100152 is M. 337. The antibody or antigen-binding fragment according to any one of Embodiments 293 and 321 to 336, wherein X2 of SEQ ID NO: 100152 is E. 338. The antibody or antigen-binding fragment according to any one of Embodiments 293 and 321 to 336, wherein X2 of SEQ ID NO: 100152 is I. 339. The antibody or antigen-binding fragment according to any one of Embodiments 293 and 321 to 336, wherein X2 of SEQ ID NO: 100152 is K. 340. The antibody or antigen-binding fragment according to any one of Embodiments 293 and 321 to 336, wherein X2 of SEQ ID NO: 100152 is L. 341. The antibody or antigen-binding fragment according to any one of Embodiments 293 and 321 to 336, wherein X2 of SEQ ID NO: 100152 is M. 342. The antibody or antigen-binding fragment according to any one of Embodiments 293 and 321 to 336, wherein X2 of SEQ ID NO: 100152 is Q. 343. The antibody or antigen-binding fragment according to any one of Embodiments 293 and 321 to 336, wherein X2 of SEQ ID NO: 100152 is T. 344. An antibody or antigen-binding fragment according to any one of embodiments 293, 321 to 336, wherein X2 of SEQ ID NO: 100152 is V. 345. An antibody or antigen-binding fragment according to any one of embodiments 293, 321 to 336, wherein X2 of SEQ ID NO: 100152 is W. 346. An antibody or antigen-binding fragment according to any one of embodiments 293, 321 to 336, wherein X2 of SEQ ID NO: 100152 is Y. 347. An antibody or antigen-binding fragment according to any one of embodiments 293, 321 to 346, wherein X1 of SEQ ID NO: 100155 is Q. 348. An antibody or antigen-binding fragment according to any one of embodiments 293, 321 to 346, wherein X1 of SEQ ID NO: 100155 is N. 349. An antibody or antigen-binding fragment according to any one of embodiments 293, 321 to 348, wherein X2 of SEQ ID NO: 100155 is D. 350. An antibody or antigen-binding fragment according to any one of embodiments 293, 321 to 348, wherein X2 of SEQ ID NO: 100155 is E. 351. An antibody or antigen-binding fragment according to any one of embodiments 293, 321 to 348, wherein X2 of SEQ ID NO: 100155 is H. 352. An antibody or antigen-binding fragment according to any one of embodiments 293, 321 to 348, wherein X2 of SEQ ID NO: 100155 is N. 353. An antibody or antigen-binding fragment according to any one of embodiments 293, 321 to 348, wherein X2 of SEQ ID NO: 100155 is Q. 354. An antibody or antigen-binding fragment according to any one of embodiments 293, 321 to 348, wherein X2 of SEQ ID NO: 100155 is S. 355. An antibody or antigen-binding fragment according to any one of embodiments 293, 321 to 354, wherein X3 of SEQ ID NO: 100155 is A. 356. An antibody or antigen-binding fragment according to any one of embodiments 293, 321 to 354, wherein X3 of SEQ ID NO: 100155 is G. 357. The antibody or antigen-binding fragment according to any one of embodiments 293, 321 to 356, wherein X4 of SEQ ID NO: 100155 is D. 358. The antibody or antigen-binding fragment according to any one of embodiments 293, 321 to 356, wherein X4 of SEQ ID NO: 100155 is F. 359. The antibody or antigen-binding fragment according to any one of embodiments 293, 321 to 356, wherein X4 of SEQ ID NO: 100155 is K. 360. The antibody or antigen-binding fragment according to any one of embodiments 293, 321 to 356, wherein X4 of SEQ ID NO: 100155 is N. 361. The antibody or antigen-binding fragment according to any one of embodiments 293, 321 to 356, wherein X4 of SEQ ID NO: 100155 is R. 362. The antibody or antigen-binding fragment according to any one of embodiments 293, 321 to 356, wherein X4 of SEQ ID NO: 100155 is S. 363. The antibody or antigen-binding fragment according to any one of embodiments 293, 321 to 356, wherein X4 of SEQ ID NO: 100155 is T. 364. The antibody or antigen-binding fragment according to any one of embodiments 293 to 363, which specifically binds to human TL1A. 365. 1x10 -9 M of K d The antibody or antigen-binding fragment according to embodiment 364, which specifically binds to human TL1A at K. 366. K d The antibody or antigen-binding fragment according to embodiment 365, wherein K is measured using a method selected from standard ELISA assay and SPR. 367. The antibody or antigen-binding fragment according to any one of embodiments 293 to 366, which inhibits the binding of DR3 to human TL1A. 368. The antibody or antigen-binding fragment according to any one of embodiments 293 to 367, which inhibits the binding of DcR3 to human TL1A. An antibody or antigen-binding fragment according to any of embodiments 293 to 368, which is a humanized antibody, a CDR-grafted antibody, a chimeric antibody, a Fab, a ScFv, or a combination thereof. 370. An antibody or antigen-binding fragment according to any of embodiments 293 to 369, which comprises a human CH1 domain. 371. An antibody or antigen-binding fragment according to any of embodiments 293 to 370, which comprises a human CH2 domain. 372. An antibody or antigen-binding fragment according to embodiment 371, wherein the CH2 domain comprises at least one mutation selected from L234A, L235A, and G237A, such that the CH2 domain is numbered using Kabat. 373. An antibody or antigen-binding fragment according to any of embodiments 293 to 372, which comprises a human CH3 domain. 374. A pharmaceutical composition comprising a therapeutically effective amount of an antibody or antigen-binding fragment according to any of embodiments 293 to 373 and a pharmaceutically acceptable carrier. 375. A method of treating an inflammatory disease in a subject, the method comprising administering to the subject a therapeutically effective amount of an antibody or antigen-binding fragment according to any of embodiments 293 to 373. 376. The method according to embodiment 375, wherein the inflammatory disease is an inflammatory bowel disease. 377. The method according to embodiment 376, wherein the inflammatory bowel disease comprises Crohn's disease. 378. The method according to embodiment 377, wherein the subject has been determined to be non-responsive to anti-TNFα treatment. 379. The method according to embodiment 377 or 378, wherein the subject has been determined to have 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, wherein the antibody or antigen-binding fragment is a heavy chain variable region comprising three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), and the heavy chain complementarity determining regions (a) (i) An HCDR1 comprising SEQ ID NO: 1009, (ii) an HCDR1 comprising SEQ ID NO: 100150 (wherein X1 is selected from D and E, X2 is selected from I, P, and V, X3 is selected from G, Q, S, and V, X4 is selected from F and Y, and X5 is selected from I and M), (iii) an HCDR1 selected from SEQ ID NOs: 100200 to 100295, and (iv) an HCDR1 selected from HCDR1s comprising an amino acid sequence that differs from a sequence selected from the group consisting of SEQ ID NO: 1009, 100150, and 100200 to 100295 by at most 5, 4, 3, or 2 amino acids, (b) (i) An HCDR2 comprising SEQ ID NO: 10012, and (ii) an HCDR2 selected from HCDR2s comprising an amino acid sequence that differs from SEQ ID NO: 10012 by at most 5, 4, 3, or 2 amino acids, (c) A heavy chain variable region comprising (i) an HCDR3 comprising SEQ ID NO: 10015, (ii) an HCDR3 comprising SEQ ID NO: 100152 (wherein X1 is selected from L and M, and X2 is selected from E, I, K, L, M, Q, T, V, W, and Y), (iii) an HCDR3 selected from SEQ ID NOs: 100296 to 100314, and (iv) an HCDR3 selected from HCDR3s comprising an amino acid sequence that differs from a sequence selected from the group consisting of SEQ ID NO: 10015, 100152, and 100296 to 100314 by at most 5, 4, 3, or 2 amino acids, and A light chain variable region comprising three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), wherein the light chain complementarity determining regions are (a) (i) An LCDR1 comprising SEQ ID NO: 10018, and (ii) an LCDR1 selected from LCDR1s comprising an amino acid sequence that differs from SEQ ID NO: 10018 by at most 5, 4, 3, or 2 amino acids, (b) (i) An LCDR2 comprising SEQ ID NO: 10021, and (ii) an LCDR2 selected from LCDR2s comprising an amino acid sequence that differs from SEQ ID NO: 10021 by at most 5, 4, 3, or 2 amino acids, (c) (i) An LCDR3 containing SEQ ID NO: 10024, (ii) an LCDR3 containing SEQ ID NO: 100155 (where X1 is selected from Q and N, X2 is selected from D, E, H, N, Q, and S, X3 is selected from A and G, and X4 is selected from D, F, K, N, R, S, and T), (iii) an LCDR3 selected from SEQ ID NOs: 100315 to 100482, and (iv) an LCDR3 selected from an amino acid sequence that differs from the sequence consisting of SEQ ID NOs: 10024, 100155, and 100315 to 100482 by at most 5, 4, 3, or 2 amino acids, comprising a light chain variable region An antibody or antigen-binding fragment thereof. 381. The antibody or antigen-binding fragment according to Embodiment 380, wherein HCDR1 contains SEQ ID NO: 100150, HCDR2 contains SEQ ID NO: 10012, HCDR3 contains SEQ ID NO: 100152, LCDR1 contains SEQ ID NO: 10018, LCDR2 contains SEQ ID NO: 10021, and LCDR3 contains SEQ ID NO: 100155. 382. The antibody or antigen-binding fragment according to Embodiment 380 or 381, wherein X1 of SEQ ID NO: 100150 is D. 383. The antibody or antigen-binding fragment according to Embodiment 380 or 381, wherein X1 of SEQ ID NO: 100150 is E. 384. The antibody or antigen-binding fragment according to any one of Embodiments 380 to 383, wherein X2 of SEQ ID NO: 100150 is I. 385. The antibody or antigen-binding fragment according to any one of Embodiments 380 to 383, wherein X2 of SEQ ID NO: 100150 is P. 386. The antibody or antigen-binding fragment according to any one of Embodiments 380 to 383, wherein X2 of SEQ ID NO: 100150 is V. 387. The antibody or antigen-binding fragment according to any one of Embodiments 380 to 386, wherein X3 of SEQ ID NO: 100150 is G. 388. The antibody or antigen-binding fragment according to any one of Embodiments 380 to 386, wherein X3 of SEQ ID NO: 100150 is Q. The antibody or antigen-binding fragment according to any one of Embodiments 380 to 386, wherein X3 of SEQ ID NO: 100150 is S. The antibody or antigen-binding fragment according to any one of Embodiments 380 to 386, wherein X3 of SEQ ID NO: 100150 is V. The antibody or antigen-binding fragment according to any one of Embodiments 380 to 390, wherein X4 of SEQ ID NO: 100150 is F. The antibody or antigen-binding fragment according to any one of Embodiments 380 to 390, wherein X4 of SEQ ID NO: 100150 is Y. The antibody or antigen-binding fragment according to any one of Embodiments 380 to 392, wherein X5 of SEQ ID NO: 100150 is I. The antibody or antigen-binding fragment according to any one of Embodiments 380 to 392, wherein X5 of SEQ ID NO: 100150 is M. The antibody or antigen-binding fragment according to any one of Embodiments 380 to 394, wherein X1 of SEQ ID NO: 100152 is L. The antibody or antigen-binding fragment according to any one of Embodiments 380 to 394, wherein X1 of SEQ ID NO: 100152 is M. The antibody or antigen-binding fragment according to any one of Embodiments 380 to 396, wherein X2 of SEQ ID NO: 100152 is E. The antibody or antigen-binding fragment according to any one of Embodiments 380 to 396, wherein X2 of SEQ ID NO: 100152 is I. The antibody or antigen-binding fragment according to any one of Embodiments 380 to 396, wherein X2 of SEQ ID NO: 100152 is K. The antibody or antigen-binding fragment according to any one of Embodiments 380 to 396, wherein X2 of SEQ ID NO: 100152 is L. The antibody or antigen-binding fragment according to any one of Embodiments 380 to 396, wherein X2 of SEQ ID NO: 100152 is M. 402. The antibody or antigen-binding fragment according to any one of Embodiments 380 to 396, wherein X2 of SEQ ID NO: 100152 is Q. 403. The antibody or antigen-binding fragment according to any one of Embodiments 380 to 396, wherein X2 of SEQ ID NO: 100152 is T. 404. The antibody or antigen-binding fragment according to any one of Embodiments 380 to 396, wherein X2 of SEQ ID NO: 100152 is V. 405. The antibody or antigen-binding fragment according to any one of Embodiments 380 to 396, wherein X2 of SEQ ID NO: 100152 is W. 406. The antibody or antigen-binding fragment according to any one of Embodiments 380 to 396, wherein X2 of SEQ ID NO: 100152 is Y. 407. The antibody or antigen-binding fragment according to any one of Embodiments 380 to 406, wherein X1 of SEQ ID NO: 100155 is Q. 408. The antibody or antigen-binding fragment according to any one of Embodiments 380 to 406, wherein X1 of SEQ ID NO: 100155 is N. 409. The antibody or antigen-binding fragment according to any one of Embodiments 380 to 408, wherein X2 of SEQ ID NO: 100155 is D. 410. The antibody or antigen-binding fragment according to any one of Embodiments 380 to 408, wherein X2 of SEQ ID NO: 100155 is E. 411. The antibody or antigen-binding fragment according to any one of Embodiments 380 to 408, wherein X2 of SEQ ID NO: 100155 is H. 412. The antibody or antigen-binding fragment according to any one of Embodiments 380 to 408, wherein X2 of SEQ ID NO: 100155 is N. 413. The antibody or antigen-binding fragment according to any one of Embodiments 380 to 408, wherein X2 of SEQ ID NO: 100155 is Q. 414. The antibody or antigen-binding fragment according to any one of Embodiments 380 to 408, wherein X2 of SEQ ID NO: 100155 is S. An antibody or antigen-binding fragment according to any one of embodiments 380 to 414, wherein X3 of SEQ ID NO: 100155 is A. An antibody or antigen-binding fragment according to any one of embodiments 380 to 414, wherein X3 of SEQ ID NO: 100155 is G. An antibody or antigen-binding fragment according to any one of embodiments 380 to 416, wherein X4 of SEQ ID NO: 100155 is D. An antibody or antigen-binding fragment according to any one of embodiments 380 to 416, wherein X4 of SEQ ID NO: 100155 is F. An antibody or antigen-binding fragment according to any one of embodiments 380 to 416, wherein X4 of SEQ ID NO: 100155 is K. An antibody or antigen-binding fragment according to any one of embodiments 380 to 416, wherein X4 of SEQ ID NO: 100155 is N. An antibody or antigen-binding fragment according to any one of embodiments 380 to 416, wherein X4 of SEQ ID NO: 100155 is R. An antibody or antigen-binding fragment according to any one of embodiments 380 to 416, wherein X4 of SEQ ID NO: 100155 is S. An antibody or antigen-binding fragment according to any one of embodiments 380 to 416, wherein X4 of SEQ ID NO: 100155 is T. An antibody or antigen-binding fragment according to any one of embodiments 380 to 416, which specifically binds to human TL1A. 425.1x10 -9 M of K d The antibody or antigen-binding fragment according to embodiment 424, which specifically binds to human TL1A at. 426.K d The antibody or antigen-binding fragment according to embodiment 425, wherein K is measured using a method selected from standard ELISA assay and SPR. An antibody or antigen-binding fragment according to any one of embodiments 380 to 426, which inhibits the binding of DR3 to human TL1A. An antibody or antigen-binding fragment according to any of embodiments 380 to 427 that inhibits the binding of DcR3 to human TL1A. An antibody or antigen-binding fragment according to any of embodiments 380 to 428, which is a humanized antibody, a CDR-grafted antibody, a chimeric antibody, a Fab, an ScFv, or a combination thereof. An antibody or antigen-binding fragment according to any of embodiments 380 to 429 that comprises a human CH1 domain. An antibody or antigen-binding fragment according to any of embodiments 380 to 430 that comprises a human CH2 domain. An antibody or antigen-binding fragment according to embodiment 431, wherein the CH2 domain comprises at least one mutation selected from L234A, L235A, and G237A, such that the CH2 domain is numbered using Kabat. An antibody or antigen-binding fragment according to any of embodiments 380 to 432 that comprises a human CH3 domain. A pharmaceutical composition comprising a therapeutically effective amount of an antibody or antigen-binding fragment according to any of embodiments 380 to 433 and a pharmaceutically acceptable carrier. A method of treating an inflammatory disease in a subject, the method comprising administering to the subject a therapeutically effective amount of an antibody or antigen-binding fragment according to any of embodiments 380 to 433. The method according to embodiment 435, wherein the inflammatory disease is an inflammatory bowel disease. The method according to embodiment 436, wherein the inflammatory bowel disease comprises Crohn's disease. The method according to embodiment 437, wherein the subject has been determined to be non-responsive to anti-TNFα treatment. The method according to embodiment 437 or 438, wherein the subject has been determined to have a disease phenotype that includes non-stricturing / non-penetrating, stricturing, stricturing and penetrating, or isolated internal penetrating. An antibody or antigen-binding fragment that specifically binds to TL1A, An antibody or antigen-binding fragment 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 according to embodiment 440, wherein the heavy chain variable region comprises SEQ ID NO: 10052. 442. The antibody or antigen-binding fragment according to embodiment 440, wherein the heavy chain variable region comprises SEQ ID NO: 10054. 443. The antibody or antigen-binding fragment according to any one of embodiments 440 to 442, wherein X1 of SEQ ID NO: 10052 or SEQ ID NO: 10054 is D. 444. The antibody or antigen-binding fragment according to any one of embodiments 440 to 442, wherein X1 of SEQ ID NO: 10052 or SEQ ID NO: 10054 is E. 445. The antibody or antigen-binding fragment according to any one of embodiments 440 to 444, wherein X2 of SEQ ID NO: 10052 or SEQ ID NO: 10054 is I. 446. The antibody or antigen-binding fragment according to any one of embodiments 440 to 444, wherein X2 of SEQ ID NO: 10052 or SEQ ID NO: 10054 is P. 447. The antibody or antigen-binding fragment according to any one of embodiments 440 to 444, wherein X2 of SEQ ID NO: 10052 or SEQ ID NO: 10054 is V. 448. The antibody or antigen-binding fragment according to any one of embodiments 440 to 447, wherein X3 of SEQ ID NO: 10052 or SEQ ID NO: 10054 is G. 449. The antibody or antigen-binding fragment according to any one of embodiments 440 to 447, wherein X3 of SEQ ID NO: 10052 or SEQ ID NO: 10054 is Q. 450. The antibody or antigen-binding fragment according to any one of embodiments 440 to 447, wherein X3 of SEQ ID NO: 10052 or SEQ ID NO: 10054 is S. 451. The antibody or antigen-binding fragment according to any one of embodiments 440 to 447, wherein X3 of SEQ ID NO: 10052 or SEQ ID NO: 10054 is V. 452. The antibody or antigen-binding fragment according to any one of embodiments 440 to 451, wherein X4 of SEQ ID NO: 10052 or SEQ ID NO: 10054 is F. 453. The antibody or antigen-binding fragment according to any one of embodiments 440 to 451, wherein X4 of SEQ ID NO: 10052 or SEQ ID NO: 10054 is Y. 454. The antibody or antigen-binding fragment according to any one of embodiments 440 to 453, wherein X5 of SEQ ID NO: 10052 or SEQ ID NO: 10054 is I. 455. The antibody or antigen-binding fragment according to any one of embodiments 440 to 453, wherein X5 of SEQ ID NO: 10052 or SEQ ID NO: 10054 is M. 456. The antibody or antigen-binding fragment according to any one of embodiments 440 to 455, wherein X6 of SEQ ID NO: 10052 or SEQ ID NO: 10054 is L. 457. The antibody or antigen-binding fragment according to any one of embodiments 440 to 455, wherein X6 of SEQ ID NO: 10052 or SEQ ID NO: 10054 is M. 458. The antibody or antigen-binding fragment according to any one of embodiments 440 to 457, wherein X7 of SEQ ID NO: 10052 or SEQ ID NO: 10054 is E. 459. The antibody or antigen-binding fragment according to any one of embodiments 440 to 457, wherein X7 of SEQ ID NO: 10052 or SEQ ID NO: 10054 is I. 460. The antibody or antigen-binding fragment according to any one of embodiments 440 to 457, wherein X7 of SEQ ID NO: 10052 or SEQ ID NO: 10054 is K. 461. The antibody or antigen-binding fragment according to any one of embodiments 440 to 457, wherein X7 of SEQ ID NO: 10052 or SEQ ID NO: 10054 is L. 462. The antibody or antigen-binding fragment according to any one of embodiments 440 to 457, wherein X7 of SEQ ID NO: 10052 or SEQ ID NO: 10054 is M. 463. The antibody or antigen-binding fragment according to any one of embodiments 440 to 457, wherein X7 of SEQ ID NO: 10052 or SEQ ID NO: 10054 is Q. 464. The antibody or antigen-binding fragment according to any one of embodiments 440 to 457, wherein X7 of SEQ ID NO: 10052 or SEQ ID NO: 10054 is T. 465. The antibody or antigen-binding fragment according to any one of embodiments 440 to 457, wherein X7 of SEQ ID NO: 10052 or SEQ ID NO: 10054 is V. 466. The antibody or antigen-binding fragment according to any one of embodiments 440 to 457, wherein X7 of SEQ ID NO: 10052 or SEQ ID NO: 10054 is W. 467. The antibody or antigen-binding fragment according to any one of embodiments 440 to 457, wherein X7 of SEQ ID NO: 10052 or SEQ ID NO: 10054 is Y. 468. The antibody or antigen-binding fragment according to any one of embodiments 440 to 467, wherein X1 of SEQ ID NO: 10053 is Q. 469. The antibody or antigen-binding fragment according to any one of embodiments 440 to 467, wherein X1 of SEQ ID NO: 10053 is N. 470. The antibody or antigen-binding fragment according to any one of embodiments 440 to 469, wherein X2 of SEQ ID NO: 10053 is D. 471. The antibody or antigen-binding fragment according to any one of embodiments 440 to 469, wherein X2 of SEQ ID NO: 10053 is E. 472. The antibody or antigen-binding fragment according to any one of embodiments 440 to 469, wherein X2 of SEQ ID NO: 10053 is H. 473. The antibody or antigen-binding fragment according to any one of embodiments 440 to 469, wherein X2 of SEQ ID NO: 10053 is N. 474. The antibody or antigen-binding fragment according to any one of embodiments 440 to 469, wherein X2 of SEQ ID NO: 10053 is Q. 475. The antibody or antigen-binding fragment according to any one of embodiments 440 to 469, wherein X2 of SEQ ID NO: 10053 is S. 476. The antibody or antigen-binding fragment according to any one of embodiments 440 to 475, wherein X3 of SEQ ID NO: 10053 is A. An antibody or antigen-binding fragment according to any one of embodiments 440 to 475, wherein X3 of SEQ ID NO: 10053 is G. An antibody or antigen-binding fragment according to any one of embodiments 440 to 477, wherein X4 of SEQ ID NO: 10053 is D. An antibody or antigen-binding fragment according to any one of embodiments 440 to 477, wherein X4 of SEQ ID NO: 10053 is F. An antibody or antigen-binding fragment according to any one of embodiments 440 to 477, wherein X4 of SEQ ID NO: 10053 is K. An antibody or antigen-binding fragment according to any one of embodiments 440 to 477, wherein X4 of SEQ ID NO: 10053 is N. An antibody or antigen-binding fragment according to any one of embodiments 440 to 477, wherein X4 of SEQ ID NO: 10053 is R. An antibody or antigen-binding fragment according to any one of embodiments 440 to 477, wherein X4 of SEQ ID NO: 10053 is S. An antibody or antigen-binding fragment according to any one of embodiments 440 to 477, wherein X4 of SEQ ID NO: 10053 is T. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. An antibody or antigen-binding fragment according to any one of embodiments 440 to 496, which specifically binds to human TL1A. 498. 1x10 -9 M of K d An antibody or antigen-binding fragment according to embodiment 497, which specifically binds to human TL1A at 1x10 499. Kd The antibody or antigen-binding fragment according to embodiment 498, which is measured using a method selected from a standard ELISA assay and SPR. 500. The antibody or antigen-binding fragment according to any one of embodiments 440 to 499, which inhibits the binding of DR3 to human TL1A. 501. The antibody or antigen-binding fragment according to any one of embodiments 440 to 500, which inhibits the binding of DcR3 to human TL1A. 502. The antibody or antigen-binding fragment according to any one of embodiments 440 to 501, which is a humanized antibody, a CDR-grafted antibody, a chimeric antibody, a Fab, an ScFv, or a combination thereof. 503. The antibody or antigen...

Claims

1. 20. A method of treating an inflammatory, fibrotic, or fibrostenosing disease or condition in a subject, comprising administering to the subject a therapeutically effective amount of any of the following: rsl892231, rs56124762, rs6478109, rs2070558, rs2070561, rsl 1897732, rs6740739, rsl7796285, rs7935393, rsl2934476, rsl2457255, rs2070557, rs4246905, rsl0974900, rsl2434976, rsl6901748, rs2815844, rs889702, rs2409750, rsl541020, rs494224 8, rs12934476, rs12457255, rs2297437, rs41309367, rs10733509, rs10750 376, rs10932456, rs1326860, rs1528663, rs951279, rs9806914, rs7935393, rs1690492, rs420726, rs7759385, rs10974900, rs1326860, rs2548147, rs2815844, rs889702, rs9806914, rs7278257, or rs11221332, or an R of at least 0.85 ２ administering to the subject a therapeutically effective amount of an inhibitor of tumor necrosis factor-like cytokine 1A (TL1A) activity or expression, provided that at least three polymorphisms, including surrogate polymorphisms in linkage disequilibrium with these as determined by the method of the present invention, 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 predict a positive therapeutic response of the subject to treatment with an inhibitor of TL1A activity or expression with a positive predictive value of at least about 70%.

3. The method of claim 1, wherein the at least three polymorphisms predict a positive therapeutic response of the subject to treatment with an inhibitor of TL1A activity or expression with at least about 70% specificity.

4. The at least three polymorphisms are (a) rs6478109, rs56124762, and rs1892231; (b) rs6478109, rs56124762, and rs16901748; (c) rs6478109, rs1892231, and rs16901748; (d) rs56124762, rs1892231, and rs16901748; (e) rs6478109, rs2070558, and rs1892231; (f) rs6478109, rs2070558, and rs16901748; (g) rs6478109, rs1892231, and rs16901748; (h) rs2070558, rs1892231, and rs16901748; (i) rs6478109, rs2070561, and rs1892231; (j) rs6478109, rs2070561, and rs16901748; (k) rs6478109, rs1892231, and rs16901748; (l) rs2070561, rs1892231, and rs16901748, (m) rs6478109, rs7935393, and rs1892231; (n) rs6478109, rs7935393, and rs9806914, (o) 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, (v) 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) rs7935393, rs9806914, and rs2070557, (bb) rs7935393, rs7278257, and rs2070557, (cc) rs1892231, rs9806914, and rs7278257, (dd) rs1892231, rs9806914, and rs2070557, (ee) rs1892231, rs7278257, and rs2070557, or (ff) rs9806914, rs7278257, and rs2070557 The method of claim 1 , comprising:

5. The at least three polymorphisms are further selected from the group consisting of rs16901748, rs1892231, rs56124762, rs6478109, rs2070558, rs2070561, rs11897732, rs6740739, rs17796285, rs7935393, rs12934476, rs12457255, rs2070557, rs4246905, rs10974900, rs12434976, rs2815844, rs889702, rs2409750, rs1541020, rs4942248, and rs1293447. 6, rs12457255, rs2297437, rs41309367, rs10733509, rs10750376, rs10932456, rs1326860, rs1528663, rs951279, rs9806914, rs7935393, rs1690492, rs420726, rs7759385, rs10974900, rs1326860, rs2548147, rs2815844, rs889702, rs9806914, rs7278257, or rs11221332, or an R of at least 0.

85. ２ 2. The method of claim 1, further comprising a fourth polymorphism comprising a surrogate polymorphism in linkage disequilibrium therewith as determined by a genomic DNA sequence encoding the nucleotide sequence of claim 1, or a combination thereof.

6. 2. The 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 the 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. 2. The method of claim 1, wherein the inflammatory, fibrotic, or fibrostenosing disease or condition comprises inflammatory bowel disease, Crohn's disease, obstructive Crohn's disease, ulcerative colitis, intestinal fibrosis, intestinal fibrotic strictures, rheumatoid arthritis, or primary sclerosing cholangitis.

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

9. 2. The method of claim 1, wherein the subject exhibits or is at risk of developing non-response or loss of response to standard of care therapy, including glucocorticosteroids, anti-TNF therapeutics, anti-a4-b7 therapeutics, anti-IL12p40 therapeutics, or combinations thereof.

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

11. 1. A method of treating an inflammatory, fibrotic, or fibrostenosing disease or condition in a subject, comprising: (a) determining whether a subject with an inflammatory, fibrotic, or fibrostenosing disease or condition is suitable for treatment with an inhibitor of TL1A activity or expression, comprising: (i) by obtaining or having obtained a sample from a subject; and (ii) rs1892231, rs56124762, rs6478109, rs2070558, rs2070561, rs1 1897732, rs6740739, rs17796285, rs7935393, rs12934476, rs1245725 5, rs2070557, rs4246905, rs10974900, rs12434976, rs16901748, rs28 15844, rs889702, rs2409750, rs1541020, rs4942248, rs12934476, rs1 2457255, rs2297437, rs41309367, rs10733509, rs10750376, rs10932456, rs1326860, rs1528663, rs951279, rs9806914, rs7935393, rs1690492, rs420726, rs7759385, rs10974900, rs1326860, rs2548147, rs2815844, rs889702, rs9806914, rs7278257, rs11221332, or an R of at least 0.85 ２ by subjecting said sample to an assay suitable for detecting at least three polymorphisms, including surrogate polymorphisms in linkage disequilibrium therewith as determined by (b) treating the subject by administering to the subject a therapeutically effective amount of an inhibitor of TL1A activity or expression; The method includes:

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

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

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

15. 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 inhibitor of TL1A activity or expression is an anti-TL1A antibody or antigen-binding fragment.

17. The at least three polymorphisms are (a) rs6478109, rs56124762, and rs1892231; (b) rs6478109, rs56124762, and rs16901748; (c) rs6478109, rs1892231, and rs16901748; (d) rs56124762, rs1892231, and rs16901748; (e) rs6478109, rs2070558, and rs1892231; (f) rs6478109, rs2070558, and rs16901748; (g) rs6478109, rs1892231, and rs16901748; (h) rs2070558, rs1892231, and rs16901748; (i) rs6478109, rs2070561, and rs1892231; (j) rs6478109, rs2070561, and rs16901748; (k) rs6478109, rs1892231, and rs16901748; (l) rs2070561, rs1892231, and rs16901748, (m) rs6478109, rs7935393, and rs1892231; (n) rs6478109, rs7935393, and rs9806914, (o) 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, (v) 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) rs7935393, rs9806914, and rs2070557, (bb) rs7935393, rs7278257, and rs2070557, (cc) rs1892231, rs9806914, and rs7278257, (dd) rs1892231, rs9806914, and rs2070557, (ee) rs1892231, rs7278257, and rs2070557, or (ff) rs9806914, rs7278257, and rs2070557 The method of claim 11 , comprising:

18. The at least three polymorphisms are further selected from the group consisting of rs16901748, rs1892231, rs56124762, rs6478109, rs2070558, rs2070561, rs11897732, rs6740739, rs17796285, rs7935393, rs12934476, rs12457255, rs2070557, rs4246905, rs10974900, rs12434976, rs2815844, rs889702, rs2409750, rs1541020, rs4942248, and rs1293447. 6, rs12457255, rs2297437, rs41309367, rs10733509, rs10750376, rs10932456, rs1326860, rs1528663, rs951279, rs9806914, rs7935393, rs1690492, rs420726, rs7759385, rs10974900, rs1326860, rs2548147, rs2815844, rs889702, rs9806914, rs7278257, or rs11221332, or an R of at least 0.

85. ２ 12. The method of claim 11 , further comprising a fourth polymorphism comprising a surrogate polymorphism in linkage disequilibrium therewith as determined by

19. 12. The method of claim 11, wherein the subject is at risk of developing non-response or loss of response to standard of care therapy, including glucocorticosteroids, anti-TNF therapeutics, anti-a4-b7 therapeutics, anti-IL12p40 therapeutics, or combinations thereof.

20. 1. A method of treating an inflammatory, fibrotic, or fibrostenosing disease or condition in a subject, comprising administering to the subject a therapeutically effective amount of an inhibitor of TL1A activity or expression, wherein the subject has a TL1A serotype of rs16901748, rs6478109, rs56124762, or an R of at least 0.

85. ２ and expressing at least three polymorphisms including a surrogate polymorphism that is in linkage disequilibrium therewith as determined by

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