Assessment of Anti-vinculin and Anti-cytolethal Distending Toxin B Antibodies in Subtypes of Irritable Bowel Syndrome
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Antibodies to cytolethal distending toxin B (CdtB) and vinculin are novel biomarkers that rule-in and differentiate irritable bowel syndrome with diarrhea (IBS-D) from other causes of diarrhea and healthy controls.
To determine whether these antibodies can also diagnose and differentiate other IBS subtypes.
Subjects with IBS-D based on Rome III criteria (n = 2375) were recruited from a large-scale multicenter clinical trial (TARGET 3). Healthy subjects without gastrointestinal (GI) diseases or symptoms (n = 43) and subjects with mixed IBS (IBS-M) (n = 25) or IBS with constipation (IBS-C) (n = 30) were recruited from two major medical centers. Plasma levels of anti-CdtB and anti-vinculin antibodies in all subjects were determined by enzyme-linked immunosorbent assay. Optical densities of ≥1.68 and ≥2.80 were considered positive for anti-vinculin and anti-CdtB, respectively. Plasma levels of anti-CdtB and anti-vinculin antibodies were highest in IBS-D and lowest in IBS-C and healthy controls (P < 0.001). Levels in IBS-C subjects were not statistically different from controls (P > 0.1). Positivity for anti-CdtB or anti-vinculin resulted in a statistically significant negative gradient from IBS-D (58.1%) to IBS-M (44.0%), IBS-C (26.7%), and controls (16.3%) (P < 0.001).
Anti-CdtB and anti-vinculin titers and positivity rates differ in IBS subtypes, with higher antibody levels and positivity rates in IBS-D and IBS-M, and lower levels in IBS-C subjects that are similar to those in healthy controls. These antibodies appear useful in the diagnosis of IBS-M and IBS-D, but not IBS-C. Furthermore, these findings suggest that IBS-C is pathophysiologically distinct from subtypes with diarrheal components (i.e., IBS-M and IBS-D).
KeywordsIrritable bowel syndrome Vinculin Cytolethal distending toxin Biomarker Constipation Diarrhea
This study was supported by funding from Commonwealth Laboratories LLC.
Compliance with ethical standards
Conflict of interest
Cedars-Sinai has licensing agreements with Valeant Pharmaceuticals International Inc., Commonwealth Laboratories Inc., and Synthetic Biologics Inc. Mark Pimentel is a consultant for Valeant Pharmaceuticals, Commonwealth Laboratories Inc., Synthetic Biologics Inc., Micropharma Inc., and Naia Pharmaceuticals and is on the advisory boards for Valeant Pharmaceuticals and Commonwealth Laboratories. Ali Rezaie is a consultant for, and has received support for teaching and research from, Commonwealth Laboratories, Actavis, and Salix Pharmaceuticals. Anthony Lembo has received fees for serving on advisory boards from Allergen, Furiex Pharmaceuticals, Prometheus Laboratories, Salix Pharmaceuticals, Valeant Pharmaceuticals, Forest Laboratories, Alkermes, AstraZeneca, and Ironwood Pharmaceuticals. The remaining authors report no conflict of interest.
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