Cedars-sinai Medical Center

Cedars-sinai Medical

Phillip R Fleshner

Stephan R Targan

Jerome I Rotter

Eric A Vasiliauskas

Huiying Yang

William S Mow

Kent D Taylor

Scott E Plevy

Gil Y Melmed

Stephen R Targan

Huiyang Yang

A common long term problem after Ileal Pouch-Anal Anastomosis (IPAA) is the inflammation of the pouch, called pouchitis. Additionally, about 5-10% of patients undergoing IPAA with a diagnosis of ulcerative colitis at the time of surgery are subsequently diagnosed with Crohn's disease. In one embodiment, the present invention provides methods of diagnosing and predicting susceptibility to pouchitis after IPAA by detecting the presence or absence of pANCA and/or Cbir1 Flagellin expression.

Ileal pouch-anal anastomosis (IPAA) factors in the treatment of inflammatory bowel disease

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

The present invention provides a method of determining a risk of pouchitis development following a surgical procedure where an internal pouch is created in a patient with ulcerative colitis. The method is practiced by determining in the patient the presence or absence of a pouchitis-associated allele linked to an interferon &ggr; receptor locus, where the presence of the pouchitis-associated allele indicates an increased risk of pouchitis development. The interferon &ggr; receptor locus to which the pouchitis-associated allele is linked can be, for example, an interferon &ggr; receptor 1 gene. A pouchitis-associated allele useful in the invention can be, for example, an allele located within the sixth intron of the interferon &ggr; receptor 1 gene, such as a FA1 microsatellite 171 allele.

Genetic testing for determining the risk of pouchitis development

Provided is a method of determining a risk of pouchitis development following a surgical procedure whereby colon is removed and an internal pouch is created in a patient with UC by determining a first pANCA titer, where the first pANCA titer is determined following the surgical procedure; determining a second pANCA titer at a later time; and comparing the first pANCA titer and the second pANCA titer, where a significantly elevated second pANCA titer indicates an increased risk of pouchitis development. Also provided is a method of determining a risk of pouchitis development following a surgical procedure whereby colon is removed and an internal pouch is created in a patient with UC by determining a first pANCA titer, where the first pANCA titer is determined prior to the surgical procedure; determining a second pANCA titer following said surgical procedure; and comparing the first pANCA titer and the second pANCA titer, where a significantly elevated second pANCA titer indicates an increased risk of pouchitis development.

Methods of determining the risk of pouchitis development

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Beverly Hills, CA, United States of America

Phillip R Fleshner