Cedars-sinai Medical Center

University of California

Other

The Uab Research Foundation

Cedars-sinai Medical

Jerome I Rotter

Stephan R Targan

Kent D Taylor

Huiying Yang

Marla C Dubinsky

Scott E Plevy

Eric A Vasiliauskas

Arthur L Beaudet

Phillip R Fleshner

Dermot McGovern

Dermot P Mcgovern

Carol J Landers

Xiuqing Guo

Ling Mei

Devendra Vora

Hiroo Toyoda

William S Mow

Betty P Tsao

Rita M Cantor

Willa A Hsueh

Leslie J Raffel

Mark O Goodarzi

Stephen R Targan

Maren Theresa Scheuner

Charles O Elson

Yii-Der Ida Chen

Talin Haritunians

Maria T Abreu

Huiyang Yang

Theresa Pizarro

Fabio Cominelli

Kazuhito Sugimura

Maren Scheuner

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.

Diagnosis and treatment of inflammatory bowel disease

The present invention relates to methods of prognosing responsiveness to anti-TNFα therapy by determining the presence or absence of risk factors in the individual. In one embodiment, the risk factors are genetic markers, serological markers and/or clinical phenotypes associated with non-responsiveness to treatment with anti-TNFα therapy in an individual diagnosed with IBD.

Methods of determining responsiveness to anti-TNFα therapy in inflammatory bowel disease

The present invention relates to methods of prognosing responsiveness to anti-TNF&#x3b1; therapy by determining the presence or absence of risk factors in the individual. In one embodiment, the risk factors are genetic markers, serological markers and/or clinical phenotypes associated with non-responsiveness to treatment with anti-TNF&#x3b1; therapy in an individual diagnosed with IBD.

Methods of determining responsiveness to anti-TNF&#x3b1; therapy in inflammatory bowel disease

Methods of using genetic variants for the diagnosis and treatment of inflammatory bowel disease

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.

Methods of predicting the need for surgery in crohn's disease

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.

Methods of predicting medically refractive ulcerative colitis (MR-UC) requiring colectomy

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.

Methods of identifying the genetic basis of a disease by a combinatorial genomics approach, biological pathway approach, and sequential approach

Disclosed is a method for determining haplotypes useful for large-scale genetic analysis, within a genomic reference sequence of interest, for a human subpopulation. The method can applied to statistically evaluating the genotypes of subjects for any statistically significant association with a phenotype of interest, such as insulin resistance or coronary artery disease. Thus, also disclosed are a method of detecting a genetic predisposition in a human subject for certain biological conditions, which may be related to coronary artery disease.

Method of haplotype-based genetic analysis for determining risk for developing insulin resistance, coronary artery disease and other phenotypes

The invention provides a method of diagnosing or predicting susceptibility to a clinical subtype of Crohn's disease in a subject having Crohn's disease by determining the presence or absence of IgA anti-I2 antibodies in the subject, where the presence of the IgA anti-I2 antibodies indicates that the subject has a clinical subtype of Crohn's disease. In one embodiment, a method of the invention is practiced by further determining the presence or absence in the subject of a NOD2 variant, anti-antibodies (ASCA), IgA anti-OmpC antibodies, or perinuclear anti-neutrophil cytoplasmic antibodies (pANCA). The methods of the invention can be used to diagnose or predict susceptibility to a clinical subtype of Crohn's disease, for example, a fibrostenotic subtype, a subtype characterized by the need for small bowel surgery, or a subtype characterized by the absence of features of ulcerative colitis.

Methods of assessing Crohn's disease patient phenotype by I2 serologic response

This invention provides methods of diagnosing or predicting susceptibility to Crohn's Disease by determining the presence or absence of genetic variants. In one embodiment, the present invention provides methods to diagnose and/or predict susceptibility to Crohn's Disease in an individual by determining the presence or absence of anti-Cbir1 reactivity and the presence or absence of TLR5 risk variants. In another embodiment, the present invention provides methods to diagnose Crohn's Disease by determining the presence or absence of NFKB1 haplotype H3 and/or ASCA expression. In another embodiment, the present invention provides methods of diagnosing Crohn's Disease by determining the presence or absence of Cbir1 specific peripheral blood T cell proliferation.

Characterization of the CBir1 antigenic response for diagnosis and treatment of Crohn's disease

The present invention provides a method of diagnosing or predicting susceptibility to a clinical subtype of Crohn's disease characterized by fibrostenosing disease by determining the presence or absence in an individual of a fibrostenosis-predisposing allele linked to a NOD2/CARD15 locus, where the presence of the fibrostenosis-predisposing allele is diagnostic of or predictive of susceptibility to the clinical subtype of Crohn's disease characterized by fibrostenosing disease. In a method of the invention, the clinical subtype of Crohn's disease can be, for example, characterized by fibrostenosing disease independent of small bowel involvement. The invention also provides a method of optimizing therapy in an individual by determining the presence or absence in the individual of a fibrostenosis-predisposing allele linked to a NOD2/CARD15 locus, diagnosing individuals in which the fibrostenosis-predisposing allele is present as having a fibrostenosing subtype of Crohn's disease, and treating the individual having a fibrostenosing subtype of Crohn's disease based on the diagnosis.

Mutations in NOD2 are associated with fibrostenosing disease in patients with Crohn's disease

The present invention provides a method of diagnosing or predicting susceptibility to an autoimmune disease in an individual by determining the presence or absence in the individual of a 2-2-4 haplotype at the Notch4, HSP70-HOM and D6S273 loci, where the presence of the haplotype diagnoses or predicts susceptibility to the autoimmune disease. The methods of the invention can be particularly useful for diagnosing or predicting susceptibility to Crohn's disease, rheumatoid arthritis or type I diabetes mellitus. In a preferred embodiment, a method of the invention is used to diagnose or predict susceptibility to Crohn's disease in an individual of Ashkenazi Jewish ethnicity.

Methods of using a major histocompatibility complex class III haplotype to diagnose Crohn's disease

Disclosed is a method for determining haplotypes useful for large-scale genetic analysis, within a genomic reference sequence of interest, for a human subpopulation. The method can applied to statistically evaluating the genotypes of subjects for any statistically significant association with a phenotype of interest, such as insulin resistance or coronary artery disease. Thus, also disclosed are a method of detecting a genetic predisposition in a Mexican-American human subject for developing insulin resistance and methods of detecting a lower than normal risk in a Mexican-American human subject for developing insulin resistance or coronary artery disease.

Method of haplotype-based genetic analysis for determining risk for developing insulin resistance and coronary artery disease

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Los Angeles, CA, United States of America

Jerome I Rotter