Researchers complete large-scale validation of biomarker for diagnosis of IBS-D

Researchers have completed the first large-scale validation of anti-cytolethal distending toxin B and anti-vinculin antibodies as a mechanism-based biomarker for diarrhea-predominant irritable bowel syndrome, according to data released in advance of Digestive Disease Week.

“Basically, for the first time, we have a biomarker that can help to make an accurate diagnosis of IBS,” Mark Pimentel, MD, from Cedars-Sinai Medical Center in Los Angeles, told Healio Gastroenterology. “The biomarker is based on a cause of IBS, food poisoning that leads to autoimmunity.”

Mark Pimentel

To determine the optimal threshold predictive of diarrhea-predominant IBS (IBS-D), Pimentel and colleagues used an enzyme-linked immunosorbent assay to evaluate plasma levels of anti-cytolethal distending toxin B (CdtB) and anti-vinculin antibodies in 2,375 patients with IBS recruited from the TARGET 3 study (a large multicenter clinical trial for IBS-D) compared with 142 patients with inflammatory bowel disease (Crohn’s disease, n = 73; ulcerative colitis, n = 69), 121 patients with celiac disease and 43 healthy controls. The primary endpoint was the antibodies’ ability to distinguish IBS from IBD.

They found the antibody titers were highest in patients with IBS compared with all other groups individually or collectively (P < .00001). For differentiating IBS-D from IBD, the area under the receiver operating curves were 0.81 for anti-CdtB and 0.62 for anti-vinculin.

The optimal cutoff point for anti-CdtB to differentiate IBS from IBD was an optical density of at least 2.8, which performed with 91.6% specificity, 43.7% sensitivity and a positive likelihood ratio of 5.2. The optimal cutoff point for anti-vinculin to differentiate IBS from IBD was an optical density of at least 1.68, which performed with 83.8% specificity, 32.6% sensitivity and a positive likelihood ratio of 2. Both tests also were significant but less specific for distinguishing IBS-D from celiac disease.

“This study validates the presence of anti-vinculin and anti-CdtB as blood-based biomarkers that separate [IBS-D] from IBD and healthy controls,” the researchers wrote. “Anti-vinculin and anti-CdtB antibodies also appear part of the pathophysiology of post-infectious IBS and may identify a subgroup of [IBS-D] for directed therapies.”

“For the 40 million people in the U.S. with IBS, this is the first time we can say you have a real disease, not just a syndrome,” Pimentel said.

This data will be presented at Digestive Disease Week on Sunday in Washington, D.C. – by Adam Leitenberger

References:

Pimentel M, et al. Abstract 311. Presented at: Digestive Disease Week, May 16-19, 2015; Washington, D.C.

Pimentel M, et al. PLoS One. 2015;doi:10.1371/journal.pone.0126438.

Disclosure: Pimentel reports various financial ties with Commonwealth, Entera Health, Micropharma, Naia Pharmaceuticals, Salix Pharmaceuticals, Synthetic Biologics and Synthetic Biomics. Please see the study for a full list of all other researchers’ relevant financial disclosures.