Cedars-sinai Medical Center

Prometheus Laboratories Inc.

Scott E Plevy

Stephan R Targan

Jerome I Rotter

Huiying Yang

Eric A Vasiliauskas

Hiroo Toyoda

Mary J Barry

Phillip R Fleshner

Kent Taylor

A novel association between certain tumor necrosis factor microsatellite alleles and Crohn's disease has been discovered. In accordance with the present invention, there is provided methods for screening for Crohn's disease comprising detecting the presence or absence of nucleic acid of a subject encoding TNF microsatellite alleles associated with Crohn's disease, wherein the presence of nucleic acid encoding three or more of the alleles is indicative of Crohn's disease. Kits useful for screening for Crohn's disease are also provided which comprise nucleic acid encoding TNF microsatellite alleles associated with Crohn's disease.

Methods of screening for Crohn's disease using TNF microsatellite alleles

The present invention provides methods based on serological and genetic markers for diagnosing clinical subtypes of Crohn's disease (CD) having characteristic responsiveness to anti-Th1 cytokine therapy. In the methods of the inventions the presence of perinuclear anti-neutrophil antibody (pANCA), the presence of the TNFa10b4c1d3e3 haplotype or the presence TNFa11b4c1d3e3 haplotype each are independently diagnostic of a clinical subtype of CD having an inferior clinical response to anti-Th1 cytokine therapy. In addition, the presence of the homozygous TNF-&bgr; 1111 haplotype involving the TNFc, aa13L, aa26 and NcoI loci is independently diagnostic of a clinical subtype of CD having an inferior clinical response to anti-Th1 cytokine therapy. The presence of speckling anti-pan polymorphonuclear antibody (SAPPA) is diagnostic of a clinical subtype of CD having a superior clinical response to anti-Th1 cytokine therapy.

Methods of diagnosing clinical subtypes of crohn's disease with characteristic responsiveness to anti-Th1 cytokine therapy

The present invention provides serological and genetic methods of diagnosing a medically resistant clinical subtype of ulcerative colitis UC. The present invention provides a method of diagnosing a medically resistant clinical subtype of UC by determining the presence or absence of anti-Saccharomyces cerevisiae antibodies (ASCA) in a patient with UC, where the presence of ASCA indicates the medically resistant clinical subtype of UC. The present invention also provides a method of diagnosing a medically resistant clinical subtype of UC by determining the presence or absence of a TNFa2b1c2d4e1 haplotype in a patient with UC, where the presence of said TNFa2b1c2d4e1 haplotype indicates the medically resistant clinical subtype of UC. In addition, the invention provides a method of diagnosing a medically resistant clinical subtype of UC by determining the presence or absence of a TNFa2b1c2d4e1 haplotype in a patient with UC and determining the presence or absence of ASCA in the patient with UC, where the presence of said TNFa2b1c2d4e1 haplotype indicates the medically resistant clinical subtype of UC and the presence of ASCA independently indicates the medically resistant clinical subtype of UC. The invention further provides kits for diagnosing a medically resistant clinical subtype of UC containing antigen specific for ASCA and one or more oligonucleotide primers complementary to a nucleotide sequence flanking TNF microsatellite locus TNFa, TNFb, TNFc, TNFd or TNFe.

Methods of diagnosing a medically resistant clinical subtype of

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

Provided herein is a method of diagnosing a clinical subtype of Crohn's disease (CD) by determining whether perinuclear anti-neutrophil antibody (pANCA) is present in a patient with CD, where the presence of pANCA indicates a clinical subtype of CD with features of ulcerative colitis (UC). Also provided is a method of diagnosing a clinical subtype of Crohn's disease in a patient with CD by determining whether pANCA or speckling anti-pan polymorphonuclear antibody (SAPPA) is present in the patient with CD, where the presence of pANCA indicates a clinical subtype of CD with features of ulcerative colitis and where the presence of SAPPA indicates a clinical subtype of CD having perforating, fistulizing or small bowel obstructive disease. The invention further provides a method of diagnosing a clinical subtype of Crohn's disease in a patient with CD by determining the presence or absence of ANCA, pANCA, SAPPA and anti-Saccharomyces cerevisiae antibodies (ASCA) in the patient with CD, where the presence of pANCA combined with the absence of ASCA indicate a clinical subtype of CD with features of UC, the presence of SAPPA indicates a clinical subtype of CD having perforating or fistulizing disease or small bowel obstructive disease, and the presence of ASCA combined with the absence of ANCA indicates a clinical subtype of CD lacking features of ulcerative colitis and having perforating or fistulizing disease or small bowel obstructive disease. Kits for diagnosing a clinical subtype of Crohn's disease, which contain neutrophil and antigen specific for ASCA, also are provided.

Methods of diagnosing clinical subtypes of crohn's disease

The present invention provides a method of diagnosing a clinical subtype of Crohn's disease (CD) by determining whether perinuclear anti-neutrophil antibodies (pANCA) are present in a patient with CD, where the presence of pANCA indicates the clinical subtype of CD with features of ulcerative colitis (UC). The invention also provides a method of diagnosing a clinical subtype of CD by detecting an Arg.sup.241 allele at an ICAM-1 locus in a patient with CD, where the Arg.sup.241 allele indicates a clinical subtype of CD with features of ulcerative colitis. In addition, the invention provides a method of diagnosing a pANCA-positive subtype of CD by detecting an Arg.sup.241 allele at an ICAM-1 locus in a patient with CD, where the Arg.sup.241 allele indicates the pANCA-positive subtype of CD.

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Pacific Palisades, CA, United States of America

Scott E Plevy