Abstract: Disclosed herein are methods, kits and compositions for treating an inflammatory disease. These methods. kits and compositions may be particularly useful for subjects carrying a risk genotype and/or expressing a transcriptomic risk signature that is indicative of severe inflammatory disease phenotypes for which existing treatment options are limited.

Abstract: A Provided herein are methods and compositions for patient selection and therapies targeting TL1A. In particular, provided is a method of treating moderate to severely active Crohn's disease (CD) or ulcerative colitis (UC) in a subject, the method comprising: administering a therapeutically effective amount of an inhibitor of Tumor necrosis factor-like cytokine 1A (TL1A) activity or expression to a subject with moderately to severely active CD or UC that has been determined have a polygenetic risk score (PRS) in the 75th percentile, which is indicative of high fold-change of TL1A expression relative to a cut-off fold-change value. Calculating a PRS comprises providing genomic data comprising one or more genotypes (e.g. rs11221332, rs7134599, rs6062496, rs4246905, rs7468800, rs1569328, rs2284553, rs6062504, and rs7556897) of the subject associated with high TL1A fold-change relative to an index or a control.

Abstract: Described herein are methods and systems for identifying subpopulations of inflammatory bowel disease (IBD) patients utilizing genetic markers that are associated with severe Crohn's disease. Further provided are therapies useful for treating these subpopulations of IBD patients based, at least in part, on the genetic markers provided herein.

Abstract: Disclosed herein are methods, kits and compositions for treating an inflammatory disease or condition, or fibrosis in a subject that has been determined to have increased fold-change in Tumor necrosis factor (TNF)-like cytokine 1A (TL1A) expression based, at least partially, on a presence of a combination of genotypes detected in a sample obtained from the subject. In some embodiments, the combination of genotypes is significantly associated with the increased fold-change in TL1A, and in some cases, may also be predictive of severe forms of the inflammatory disease or condition. In some embodiments, the inflammatory disease or condition is an inflammatory bowel disease, such as Crohn's disease or ulcerative colitis.

Abstract: Provided herein are methods, systems and kits for use in identifying a subject with an increased risk of developing severe forms of inflammatory bowel disease (IBD), based at least in part, on an expression of one or more biomarkers detected in a biological sample obtained from the subject. Also provided are methods, systems and kits for treating, or optimizing the treatment for, the IBD based, at least in part, on the expression the one or more biomarkers. In some embodiments, the one or more biomarkers is angiotensin-converting enzyme 2 (ACE2), the host receptor for severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2).

Abstract: Disclosed herein are methods, kits and compositions for treating an inflammatory disease. These methods, kits and compositions may be particularly useful for subjects carrying a risk genotype and/or expressing a transcriptomic risk signature that is indicative of severe inflammatory disease phenotypes for which existing treatment options are limited.

Abstract: Described herein are methods and systems for identifying subjects suitable for treatment with an inhibitor of CD30L activity or expression, such as an anti-CD30L antibody. Methods and systems disclosed herein identify subjects suitable for treatment based on a presence of a genotype that is indicative of a disease or condition in the subject for which an inhibitor of CD30L is a suitable treatment. Exemplary conditions include both Crohns disease and primary sclerosing cholangitis. Compositions used to detect the genotypes described herein, and methods of using them are also provided.