This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Ulcerative colitis and Crohn's disease are chronic and debiliting inflammatory conditions of the intestinal tract, collectively refered to as inflammatory bowel disease (IBD).Much progress has been made in identifying the genes associated with these inflammatory disorders. Gene scanning and candidate gene approaches have revealed several disease-associated locations on relevant genes. One important implication of gene scanning studies is that at least three loci confirmed by independent groups, and an additional three others are suggested in some manifestations of IBD. Some of these genes are associated with Crohn's disease and or ulcerative colitis individually, and others are associated with both. Marker antibodies (proteins in the blood) and/or disease expression further refines the associations. Multiple studies in the human, as well as the animal studies summarized above, have demonstrated differing genetic associations with clinical characteristics as well as marker antibody expression. While headway has been made in localizing some of the genes important in IBD, much more work is needed to find which genes are involved, especially since evidence suggests that several genes are likely to act in concert in the development of these conditions.Since the discovery of perinculear antineutrophil cytoplasmic antibodies (pANCA) ten years ago, much has been learned about the presence of marker antibodies in the serum of patients with IBD. In addition to pANCA, interest has focused on another protein in the blood called Saccharomyces cerevisiae (ASCA), which have been shown to differentiate between ulcerative colitis and Crohn's disease. Our group has not only contributed to progress on these antibodies, but has further identified two new proteins (HupB and I2) which identify strongly disease-associated antibodies in Crohn's disease. These marker antibodies are important for their diagnostic utility and stratification of patients into distinct clinical types. These antibodies are associated not only with the different locations of disease, but also with aggressiveness of disease course as well as with responses to treatment by specific manipulation of gastrointestinal (GI)immunology.Although many inflammatory proteins are elevated in the GI tract of patients with IBD, their precise role in disease disease development has never been determined. In animal models, the success of treatment by manipulation GI immunology has led to trials of anti-TNF-a for the treatment of Crohn's disease. Results of these trials showed for the first time that certain immunologic cell in the GI tract could alter disease course in the majority of patients with Crohn's disease. Sixty-five percent of patients responded dramatically to a single infusion of anti-TNF-a. A proportion of Crohn's disease patients can be treated by manipulation of the bacterial flora by either antibiotic therapy or a diversion of the fecal stream, which suggests diverse responses to bacterial antigens among the Crohn's disease population. In ulcerative colitis, patients with high levels of pANCA are three times more likely to develop chronic pouchitis than patients without high levels of pANCA. These findings, taken together, highlight the potential importance of bacterial interactions in the induction or maintenance of inflammation. Overall, the diversity of clinical expression seen in IBD is very likely dependent upon a combination of genetic abnormalities and the presence of certain commensal bacteria. In summary, this umbrella procedure will provide human tissue and associated clinical data to facilitate and expedite numerous ongoing projects aimed at identifying the causes of IBD and to identify potential therapeutic targets.The Cedars-Sinai IBD Center conducts laboratory and clinical research designed to understand the causes and improve treatments for inflammatory bowel diseases (IBD); Crohn's disease and ulcerative colitis. Numerous studies, some sponsored by the NIH or other private entities, and some unfunded at present rely on the acquisition and evaluation of tissues (blood and/or intestinal mucosa) in association with correlated clinical data. The purpose of this protocol is to establish an umbrella procedure for enrolling participants and the subsequent use and/or storage of such samples and data resulting from these studies. Dr. Abreu, one of the original study investigators has relocated to Mt. Sinai Hospital in New York. She wil be given access to unidentified specimens for ongoing analysis. As always, our tissue specimens are labeled with only the year they were obtained and the sequential number as they were acquired (e.g. 05-023). After Dr. Abreu analyzes her specimens she may request from us information pertaining to their disease (CD or UC patient), treatment, gender and biochemical marker status. At no time will she receive any identifying information (patient name, MRN, etc.). Please be assured that the only persons who have access to PHI are Dr. Targan and the study coordinators.
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