Findings from the PREDICTS study indicated that before symptoms appear, markers of Crohn’s disease can be detected. The new discovery may help to predict risk not only of disease development but also of disease complications.
The study, “Serologic microbial associated markers can predict Crohn’s disease behaviour years before disease diagnosis,” was published in the journal Alimentary Pharmacology & Therapeutics.
The research was conducted by CRADA (Cooperative Research and Development Agreement), a research collaboration between the Mayo Clinic, Mount Sinai Health System, Prometheus Laboratories, Janssen Pharmaceuticals, and the Naval Medical Research Center.
“Acquiring mechanistic information on pre-clinical IBD [inflammatory bowel disease] can potentially uncover key pathogenic events, lead to the development of new therapeutic targets and inform predictive algorithms that could be used to define at-risk populations in whom to test these approaches,” said Jean-Frédéric Colombel, M.D., co-senior author of the study and co-director of The Susan and Leonard Feinstein Inflammatory Bowel Disease Clinical Center at Mount Sinai, in a news release.
“This study adds an additional piece of evidence into ‘life before IBD,’ a major focus of research at Mount Sinai, since exploring the pre-clinical phase of inflammatory bowel disease may offer some new insights in the origin of IBD and hopefully prevention,” he said.
The researchers evaluated the pattern of serologic anti-microbial antibodies prior to an IBD diagnosis, and the subsequent risk of complicated Crohn’s disease at diagnosis. Sera from 100 U.S. military personnel with Crohn’s disease were obtained from the Department of Defense Serum Repository. For each patient, four samples were obtained at different time points before and around diagnosis, and were tested for six microbiota-directed antibodies (ASCA-IgA, ASCA-IgG, anti-OmpC, anti-CBir1, anti-A4-Fla2, and anti-FlaX). These markers were found to be circulating in patients’ serum years before diagnosis, and have been linked with disease severity when detected at the time of, or just following, diagnosis.
The results showed that these markers were present in serum up to six years prior to diagnosis (65 percent of the patients tested positive for at least one marker), and that the number of positive markers increased up to diagnosis. Patients who had a higher amount of positive antibodies, and those who had higher titers, were found to develop more recurrent complications — such as strictures, need for surgery, abscesses, or fistulas — at or around the time of diagnosis.
“This study represents an important addition to research being performed on the pre-clinical stage of IBD,” said co-senior author Joseph A. Murray from the Mayo Clinic. “This is the first time that a longitudinal assessment of antimicrobial markers in serum was performed. Furthermore, it is also the first time that a link between these markers in a pre-clinical phase and future risk for disease complications has been made.
“These findings suggest that it may be possible to identify a population of patients not only at high risk for IBD, but also for complicated disease in which preventive strategies or intensive monitoring could be applied. Further research into this stage of pre-clinical disease will likely lead to better understanding and identification of key events involved in disease pathogenesis,” Murray said.
The study is ongoing, and the researchers expect to have results soon on 1,000 Crohn’s disease patients, 1,000 patients with ulcerative colitis, and 500 healthy controls. Besides antimicrobial markers, the team also will explore other possible pre-clinical markers, including the proteomic profile and exposure to infectious agents such as viruses.