Biomarker Panel Predicts Crohn Disease Years Before Diagnosis

Levels of serum biomarkers can predict patients who will go on to develop Crohn disease (CD) up to 5 years before they are diagnosed, according to new findings.

The panel of 51 proteins and microbial antibodies had an accuracy of 76% for CD diagnosis within 5 years and 87% for diagnosis within 1 year, but was less accurate for predicting ulcerative colitis (UC), Dr. Jean-Frederic Colombel of the Icahn School of Medicine at Mount Sinai in New York City and colleagues found.

"I think this study is really groundbreaking because it is the first step in the prediction of inflammatory bowel disease (IBD)," Dr. Colombel told Reuters Health in a telephone interview.

He and his team analyzed 1,824 serum samples from the Defense Medical Surveillance System collected in 1998-2013 from 200 military recruits who later developed CD, 199 who developed UC and 200 healthy controls. Recruits were required to provide blood samples every two years, the researchers explain in Gastroenterology.

The biomarkers linked to future CD diagnosis were associated with inflammation, cell signaling, innate immunity, and response to bacteria. Proteomic analysis of predictive pathways suggested alterations in the complement cascade, innate immunity, glycosaminoglycan metabolism, and lysosome.

Based on area under the receiver operating characteristic curves (AUROC), the panel had an accuracy of 56% for predicting a UC diagnosis within 5 years and of 72% for predicting one within a year.

"In IBD there is a long preclinical phase meaning that before the first symptoms occur, there are already changes in your immune system, your microbiome, which are occurring in your gut, but which are not manifested clinically, and this is where we really want to intercept the disease," Dr. Colombel said.

He and his colleagues are working on reinforcing their predictive model by analyzing alterations in the microbiome, exposome and viromes of IBD patients, as well as intestinal permeability, and glycosylation.

"I believe we'll be entering a new era in the treatment of IBD, which is prediction and prevention," he said.

Janssen Pharmaceuticals and Prometheus Laboratories funded the research. Dr. Colombel reports financial ties to Janssen, and several of his coauthors are employed by the company. His institution and the two companies have filed a patent application for a panel of biomarkers for IBD.

—Anne Harding

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