Antibody Test Spots IBS
Published: Oct 15, 2013, By Nancy Walsh, Staff Writer, MedPage Today
SAN DIEGO -- Testing for antibodies to the protein vinculin may offer a serologic means of diagnosing irritable bowel syndrome (IBS), a researcher said here.
Measurement of anti-vinculin antibodies in serum demonstrated higher levels of these autoantibodies in IBS patients, compared with those without the disorder, with positive predictive values between 90% and 100% depending on the cutoff values used, reported Mark Pimentel, MD, of Cedars-Sinai Medical Center in Los Angeles, and colleagues.
For instance, with a cutoff using optical density above 0.8, the specificity was 81% and the positive predictive value was 93%, Pimentel said at the annual meeting of the American College of Gastroenterologyhere.
"Irritable bowel syndrome has been a diagnosis of exclusion, where we first have to rule out all sorts of other diseases and then apply the Rome criteria. But those criteria aren't specific, and in one study we found that only 67% of IBS patients met those criteria," he said.
There has not been a valid biomarker of the disorder, so most patients undergo extensive and expensive testing.
To address this diagnostic gap, he and his colleagues have been exploring the pathophysiology of IBS, and have found that in many cases, the condition arises after an episode of gastroenteritis, with bacterial overgrowth in the small intestine resulting from neuromuscular damage.
Animal models showed that a specific toxin produced by gastroenteritis-causing bacteria such as Campylobacter jejuni known as cytolethal distending toxin B (CdtB) can precipitate IBS.
So Pimentel's group developed an antibody to the CdtB toxin and applied it to full thickness biopsies of rat intestine, and found that the antibody bound strongly to all the neuromuscular elements, but in both exposed and control animals.
"So the antibodies to CdtB were reacting to something that was part of the host, not to the presence of the toxin," he explained.
Then, through a series of experiments, they considered if this was molecular mimicry, but eventually with immunoprecipitation testing determined that the antibody was targeting the human protein vinculin, which is important for nerve cell migration.
They also considered the possibility that exposure to the toxin led to the development of antibodies that could react to CdtB epitopes, and whether through homology perhaps one epitope produced an autoantibody to the protein.
"Our hypothesis was that in humans, some people never had gastroenteritis, never developed antibodies to CdtB or vinculin, and never developed IBS. Or they did have gastroenteritis, produced the antibodies, and then developed IBS," he said.
So to study the diagnostic potential of these anti-vinculin antibodies, his group recruited 165 patients with IBS, 30 with inflammatory bowel disease, and 26 healthy controls.
Patients in the three groups were similar in age and gender, with 70% being female.
They found that patients with IBS had much higher levels of anti-vinculin antibodies, whereas the patients with inflammatory bowel disease had higher levels of the anti-CdtB antibodies.
They also observed that patients who reported a history of acute gastroenteritis had even higher levels of anti-vinculin antibodies (P<0.05).
Then, in their specificity analyses, they found that compared with inflammatory bowel disease, the specificity for IBS with elevated anti-vinculin antibodies was 88% and the positive predictive value was 94%.
Therefore, this test might be able to discriminate IBS from inflammatory bowel disease as well as other conditions, he noted.
Pimentel reported no disclosures.
Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.