[Read more] A team led by Dr. Mark Pimentel, director of the Gastrointestinal Motility Program at Cedars-Sinai Medical Center in Los Angeles, conducted this multicenter study to test the test in patients with irritable bowel syndrome or inflammatory bowel disease and healthy controls. Results presented at the American College of Gastroenterology (ACG) annual meeting show that the anti-adhesive plaque protein antibody test differentiates between irritable bowel syndrome and inflammatory bowel disease in a multicenter study conducted by a team led by Mark Pimentel, MD, PhD, director of the Gastrointestinal Dynamics Program at Cedars-Sinai Medical Center in Los Angeles. The test. The findings, reported at the American College of Gastroenterology (ACG) annual meeting, showed that the anti-adhesive plaque protein antibody test had a positive predictive value of more than 90 percent for distinguishing irritable bowel syndrome from inflammatory bowel disease.
SAN DIEGO – The detection of anti-adhesive plaque protein antibodies in the blood – a protein involved in nerve cell migration – may enable an objective diagnosis of irritable bowel syndrome. The diagnosis of irritable bowel syndrome has always relied on a thorough examination to rule out other possibilities.
Moreover, if anti-cellular lethal swelling toxin B (CdtB, a toxin produced by bacteria that often cause food poisoning) antibodies are also taken into account in the analysis, the positive predictive value can be further increased to ≥94%.
“Elevated levels of anti-adhesive plaque protein antibodies are specific to irritable bowel syndrome, and elevated levels of anti-CdtB antibodies further enhance the specificity of anti-adhesive plaque egg antibody detection. This may be the first diagnostic serum biomarker that can differentiate irritable bowel syndrome from inflammatory bowel disease and will help avoid unnecessary testing.”
In addition, the findings support the mechanism of irritable bowel syndrome pathogenesis after infection derived from rodent models, in which bacterial gastroenteritis causes autoimmunity against GI adhesive plaque proteins.
Such tests may also be useful in inflammatory bowel disease research, he noted. “One of the problems with inflammatory bowel disease research is that patients who do not respond to treatment may actually have irritable bowel syndrome rather than inflammatory bowel disease. Perhaps this test could be used to screen out such patients before studies begin.”
One participant expressed reservations about the study. He noted that some analyses were performed comparing patients with irritable bowel syndrome to healthy individuals, and given the composition of the study’s subject population, a positive predictive value may not be the best statistical parameter. “We don’t need to do tests to know who is symptomatic and who is not. So this study is the beginning of validation, not the end. I estimated that if you put this test into clinical use right now, the positive predictive value would be about 20 percent. So it doesn’t mean much for clinical practice …… I’m sure you’ll continue to optimize this test, but I don’t think it’s ready for use in clinical practice right now.”
Dr. Pimentel replied, “First, you can use a probability ratio that indicates the proportion of patients …… We have a probability ratio between 3 – 4, and hopefully this data will make you trust the test more. Second, the people who come to the office are not healthy: if they have symptoms of diarrhea, it suggests inflammatory bowel disease or irritable bowel syndrome or some other disease.”
In a press release, Dr. Brian E. Lacy of Dartmouth-Hitchcock Medical Center commented, “This is a very important topic. According to conservative estimates, 12 – 15 percent of the population has irritable bowel syndrome, and $20 – 30 billion is spent annually on diagnosing and treating irritable bowel syndrome.”
“For many patients, irritable bowel syndrome is a diagnosis of exclusion. They will go through a battery of unnecessary tests and often find nothing because it is a functional bowel disease.” He added, “If there was a blood test that could confirm the diagnosis of irritable bowel syndrome, I think that would be very important. Community physicians and family physicians often don’t have the confidence to make a diagnosis of irritable bowel syndrome, and with such a diagnostic test, they might say, ‘This is a great test, and we can not only make a diagnosis, but we can rule out inflammatory bowel disease or improve our ability to rule out patients with inflammatory bowel disease. “
Dr. Pimentel believes the test may also be revealing for treatment. “Another question is, can this antibody test predict who will respond to antibiotic therapy, or can it predict bacterial overgrowth or other treatable manifestations of irritable bowel syndrome?”
Finally, such a test would also help prove that irritable bowel syndrome is indeed a disease. “Irritable bowel syndrome is a very, very difficult disease to deal with because none of us know much about it, and because it is often considered a lifestyle disorder rather than a disease, irritable bowel syndrome has received some ‘unfair’ treatment.” He commented, “So I hope to bring awareness to the fact that irritable bowel syndrome is a real disease, not just a syndrome.”
In this study, the researchers prospectively identified 162 patients who met the diagnostic criteria for Rome III irritable bowel syndrome, and serum samples from these patients were measured. Thirty patients with active inflammatory bowel disease who were not using biologics at the time and 26 consecutively enrolled healthy individuals were also included. Approximately 70% of the patients in all groups were female, with no significant differences in age or gender distribution.
The results showed that patients with irritable bowel syndrome had higher optical density (OD) readings of anti-adhesive plaque protein antibodies than patients with inflammatory bowel disease (P<0.01) and healthy individuals (P<0.01). Also, the OD readings of anti-CdtB antibodies were higher in patients with inflammatory bowel disease than in patients with irritable bowel syndrome (P=0.02). In distinguishing irritable bowel syndrome from inflammatory bowel disease, anti-CdtB antibody OD readings above 0.8 had a sensitivity of 43%, specificity of 73%, and a positive predictive value of 90%. As to why both anti-CdtB and anti-adhesive plaque protein antibodies were tested, Dr. Pimentel reasoned that in the post-infection irritable bowel syndrome model, anti-adhesive plaque protein antibodies persist, while anti-CdtB antibodies decrease over time. In fact, in this study, the difference between the OD readings of these two antibodies (anti-adhesive plaque protein antibody-anti-CdtB antibody) was higher in patients with irritable bowel syndrome, P<0.0001 compared to patients with inflammatory bowel disease and P<0.001 compared to healthy subjects. In distinguishing irritable bowel syndrome from inflammatory bowel disease, the difference exceeded 0.2 with a sensitivity of 41% and a specificity of 88% The positive predictive value was 94%. Dr. Pimentel noted that one confounding issue is that about 10% of patients with inflammatory bowel disease also have irritable bowel syndrome. However, in a model that takes this into account, anti-adhesive plaque protein antibodies with OD readings above 0.8 (92%) and a difference in OD readings between the two antibodies above 0.2 (97%) still had a high positive predictive value.