Abstract: The invention provides models of various conditions including but not limited to intestinal inflammation and/or fibrosis, inflammatory bowel disease, colitis, acute colitis, and chronic colitis, and methods of using such models for designing, screening and developing therapeutics for those conditions. The invention also provides methods, compositions, and kits for treating those conditions.

Abstract: The present invention relates to methods of predicting susceptibility to a severe form of Crohn's disease in an individual by determining the presence or absence of one or more risk variants. In one embodiment, the risk variants comprise a combination of genetic risk variants and clinical risk factors. In another embodiment, the genetic risk variants are at the IL12B genetic locus. In another embodiment, the severe form of Crohn's disease is characterized by a rapid progression to a condition requiring surgery for treatment.

Abstract: The present invention relates to methods of predicting susceptibility to a severe form of Crohn's disease in an individual by determining the presence or absence of one or more risk variants. In one embodiment, the risk variants comprise a combination of genetic risk variants and clinical risk factors. In another embodiment, the genetic risk variants are at the IL12B genetic locus. In another embodiment, the severe form of Crohn's disease is characterized by a rapid progression to a condition requiring surgery for treatment.

Abstract: The present invention describes methods for treating inflammatory disorders of the gastrointestinal tract, including but not limited to Inflammatory Bowel Disease (IBD), Crohn's Disease (CD), Ulcerative Colitis (UC) and/or medically refractory ulcerative colitis (MR-UC) using anti-IFNG therapy. The present invention also describes a process for patient risk stratification.

Abstract: This invention provides methods of diagnosing or predicting susceptibility to Inflammatory Bowel Disease by determining the presence or absence of genetic variants in the TL1A gene. In one embodiment, a method of the invention is practiced by determining the presence or absence of TL1A production following Fc-gamma-R activation. In another embodiment, the invention provides methods of treatment of inflammatory bowel disease by inhibition of TL1A.

Abstract: Disclosed are methods of predicting the development of medically refractory ulcerative colitis (MR-UC) in a patient In one embodiment, disclosed is a method of prognosing ulcerative colitis in an individual by determining the presence or absence of one or more risk variants, where the presence of one or more risk variants is indicative of a severe and/or aggressive form of ulcerative colitis. In another embodiment, the severe form of ulcerative colitis is indicative of MR-UC.

Abstract: The present invention relates to methods of predicting the risk for colectomy in a subject with mrUC, by determining the presence or absence of one or more mrUC risk variants. Other embodiment, relate to methods of treating mrUC in a subject and a kit for prognostic use.

Abstract: Compositions and methods for the therapy and diagnosis of Inflammatory Bowel Disease (IBD), including Crohn's Disease and Ulcerative Colitis, are disclosed. Illustrative compositions comprise one or more bacterial polypeptides, immunogenic portions thereof, polynucleotides that encode such polypeptides, antigen presenting cell that expresses such polypeptides, and T cells that are specific for cells expressing such polypeptides. The disclosed compositions are useful, for example, in the diagnosis, prevention and/or treatment of IBD.

Abstract: The present invention relates to the finding that TL1A enhances differentiation of TH17 cells, and enhance IL17 secretion from TH17 cells. In one embodiment, the present invention provides a method of treating an inflammatory disease comprising determining the presence of a TL1A signaling profile, and treating the disease by administering a composition comprising a therapeutically effective dosage of one or more inhibitors of TL1A or TH17 cell differentiation. In another embodiment, the disease is characterized by TH17 differentiation.

Abstract: The present invention relates to biomarker genes for diagnosing and treating diseases. Provided herein are systems and methods of diagnosing a disease in a patient based on the patient's expression levels of biomarker genes. Examples of the TL1A-associated disease include, but are not limited to, an inflammatory bowel disease (IBD), Crohn's disease (CD), ulcerative colitis (UC), and fibrosis. Also provided herein are systems and methods of identifying a patient likely to be responsive to an anti-TL1A therapy, prescribing and/or administrating an anti-TL1A therapy to the patient based on the patient's expression levels of biomarker genes.

Abstract: This invention relates transgenic animals that overexpress TL1A in a tissue specific manner to model inflammatory bowel disease (IBD), such as colitis, Crohn's disease and ulcerative colitis, fibrosis, and related inflammatory diseases and conditions. TL1A transgenic animals constitutively express both TL1A and GFP in lymphoid and myeloid cell lineages, allowing convenient identification and sorting of immune cells involved in IBD disease progression, such as T-cells, antigen presenting cells (APC), and dendritic cells (DC). TL1A transgenic animals may be induced to exhibit gross fibrosis, or isolated cells may be implanted into immunodeficient mice to establish colitis.

Abstract: Described herein are methods and compositions related to Inflammatory Bowel Disease. Specifically TL1A drives regional intestinal inflammation and fibrosis and is differentially modulated by IFN gamma and IL-17a. In one embodiment, the present invention is a method of diagnosing a condition in a subject by determining the presence or absence of IFN gamma and/or IL-17 and diagnosing the subject.

Abstract: In one embodiment, the invention provides methods of identifying genes and genetic variants that, either alone or in combination, are important to the pathogenesis of a disease. In another embodiment, the disease is stratified by use of an immune response to disease-associated antigens. In another embodiment, the invention provides methods of identifying pathways that, either alone or in combination, are important to the pathogenesis of a disease. In another embodiment, the invention provides a method of diagnosing or predicting susceptibility to a disease in an individual by determining the presence or absence of genes and genetic variants that, either alone or in combination, are important to the pathogenesis of the disease.

Abstract: Compositions and methods for the therapy and diagnosis of Inflammatory Bowel Disease (IBD), including Crohn's Disease and Ulcerative Colitis, are disclosed. Illustrative compositions comprise one or more bacterial polypeptides, immunogenic portions thereof, polynucleotides that encode such polypeptides, antigen presenting cell that expresses such polypeptides, and T cells that are specific for cells expressing such polypeptides. The disclosed compositions are useful, for example, in the diagnosis, prevention and/or treatment of IBD.

Abstract: The invention relates to methods of treating fibrosis and inflammatory bowel disease. In one embodiment, the present invention treats gut inflammation by administering a therapeutically effective dosage of TL1A inhibitors and/or DR3 inhibitors to an individual. In another embodiment, the present invention provides a method of reversing tissue fibrosis in an individual by inhibiting TL1A-DR3 signaling function.

Abstract: The present invention also provides various methods, kits and compositions for diagnosing, prognosing, and treating various conditions including but not limited to inflammatory bowel diseases, such as ulcerative colitis and Crohn's disease. Also, the present invention provides various methods, kits and compositions for determining susceptibility to or a low probability of various conditions including but not limited to inflammatory bowel diseases, such as ulcerative colitis and Crohn's disease. These methods, kits and compositions may involve detecting risk/protective variants or haplotypes, serological markers, increased or decreased gene methylation, and increased or decreased cytokine secretion.

Abstract: The present invention relates to methods of diagnosing and predicting susceptibility to Crohn's Disease and/or IBD, by determining the presence or absence of susceptibility to genetic variants, risk haplotypes and/or protective haplotypes. In an embodiment, the invention provides methods of diagnosing and/or predicting susceptibility to Crohn's Disease in an individual by determining the presence or absence of risk variants at the IL12RB1, IL12RB2, IL17A, IL17RA, IL17RD and/or IL23R locus.

Abstract: This invention provides methods of diagnosis, predicting and diagnosing susceptibility to, predicting disease progression and treatment of inflammatory bowel disease (IBD), including Crohn's disease and/or subtypes of Crohn's disease (CD) and/or Ulcerative Colitis (UC). In one embodiment, a method of the invention is practiced by determining the presence or absence of the genetic variants NOD2, TLR8, TLR2, CARD8, CARD15 and/or JAK3 to diagnose, predict and diagnose susceptibility and predict disease progression in an individual. In another embodiment, a method of the invention is practiced by determining the presence or absence of anti-Cbir1, anti-OmpC, ASCA, anti-I2 and/or pANCA in an individual. In another embodiment, the invention further associates the presence or absence of the risk variants with the expression of anti-Cbir1, anti-OmpC, ASCA, anti-I2 and/or pANCA for the diagnosis, prediction of susceptibility, prediction of disease progression and/or treatment of IBD, including CD and/or UC.

Abstract: The invention relates to method of diagnosing susceptibility to inflammatory bowel disease (IBD) in an individual by obtaining a sample from the individual, assaying the sample to determine the presence or absence of one or more risk genetic variants and/or an increase in IFNG DNA methylation. In one embodiment, the present invention provides a method of diagnosing susceptibility to inflammatory bowel disease (IBD) in an individual by obtaining a sample from the individual, assaying the sample to determine the presence or absence of one or more risk genetic variants and/or an increase in IFNG DNA methylation relative to a normal subject, and diagnosing susceptibility to inflammatory bowel disease based on the presence of one or more risk genetic variants and/or an increase in IFNG DNA methylation relative to a normal subject. In another embodiment, the IBD is ulcerative colitis.

Abstract: This invention relates transgenic animals that overexpress TL1A in a tissue specific manner to model inflammatory bowel disease (IBD), such as colitis, Crohn's disease and ulcerative colitis, fibrosis, and related inflammatory diseases and conditions. TL1A transgenic animals constitutively express both TL1A and GFP in lymphoid and myeloid cell lineages, allowing convenient identification and sorting of immune cells involved in IBD disease progression, such as T-cells, antigen presenting cells (APC), and dendritic cells (DC). TL1A transgenic animals may be induced to exhibit gross fibrosis, or isolated cells may be implanted into immunodeficient mice to establish colitis.