Lay Summary
Proposal No. IBD-0095
Principal Investigator: Laura W. Lamps, M.D.
Applicant Organization: University of Arkansas for Medical Sciences (Little Rock, U.S.A.)
Project Title: Pathogenic Yersinia DNA detection in Crohn’s disease
Period of Award: January 1, 2004 – March 31, 2006
Background. Crohn’s disease (CD) is a chronic inflammatory disease of the intestines for which there is no known cause. Many different bacteria have been investigated as causes, but no direct links between specific bacteria and CD have been proven. Yersinia enterocolitica (YE) and Y. pseudotuberculosis (YP) are bacteria that are commonly found in water, milk, and meat. They are a common cause of gastroenteritis in industrialized countries. Studying Yersinia is challenging, as there are not many ways to reliably detect it. Our group developed a novel test (called a PCR assay) for detection of Yersinia, which can be used on tissues received in a pathology laboratory. Our goals for this grant are: 1) to confirm our preliminary findings by testing additional CD tissues from multiple areas of the United States; 2) to find out if certain strains (called serogroups) of Yersinia can be linked to specific areas of the country or food sources; and 3) to develop an additional test called in situ hybridization that would allow us to actually see the bacteria in CD tissue.
Materials and Methods. Pathology specimens with CD will be retrieved from multiple hospitals and tested with our assay. If cases test positive, additional testing will be undertaken to try to link specific strains of the bacteria to certain geographic regions or foods. Positive cases will also be subjected to in situ hybridization in an attempt to see the bacteria within the CD tissue. When available, a limited medical record review will be conducted.
Anticipated Results. In our preliminary studies, we found Yersinia DNA in 31% of 54 CD cases that we tested. We anticipate that we will continue to detect Yersinia in a significant number of CD patients and that we will be able to classify positive cases as to their specific strain or serogroup. We also anticipate development of an in situ hybridization assay that will allow us to visualize the bacteria within CD tissue samples.
Conclusions. Our preliminary data raise the possibility that Yersinia plays a role in the causation of CD. Some individuals may be vulnerable to bacterial "triggers" in their environment, which initiate an abnormal immune response, leading to CD. It is also conceivable that this bacterial trigger varies with population, geographic location, and food sources. In this study, we hope to further assess the presence of Yersinia DNA in CD and to link specific Yersinia serotypes with CD. It is hoped that our results will aid in the development of larger studies with possible implications for treatment.