IS A CALPROTECTIN A CALPROTECTIN: VARIATION IN CALPROTECTIN RESULTS BY METHODOLOGY

Abstract BACKGROUND Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic disorder mediated by episodes of remittent inflammation in the gastrointestinal tract and beyond. Noninvasive testing with fecal calprotectin, a neutrophil activity byproduct, is frequently used to identify patients requiring endoscopic evaluation. While notably elevated calprotectin is highly suggestive, mild elevations are less clear, and often not linked with IBD. Multiple methodologies of testing calprotectin exist, and we hypothesized that part of the 「grey area」 may come from alterations to results based on methodology. We sought to assess this by comparing testing methodology on standardized patients. METHODS We compared FDA submission data from current approved diagnostic methodologies with a novel method developed at ALPCO. We identified 76 patients diagnosed with IBD after undergoing gastrointestinal endoscopy/colonoscopy and histologic confirmation of disease. We also identified 122 patients with confirmed IBS who were diagnosed with the Rome IV criteria. We then analyzed stool samples from each of these patients using calprotectin assays and compared accuracy to previously existing endoscopic results to generate test specificity/sensitivity results. RESULTS Wide variation in results was observed using different methodologies, with substantial variation in sensitivity, specificity, and positive predictive value. (table 1). While the majority of assays had sensitivity > 90%, specificity ranged widely, with only two tests exceeding 90%. False positive rates were generally high, with only two assays < 10%. DISCUSSION Our results demonstrate a concerning degree of variation in fecal calprotectin results by methodology. Further evaluation is needed using neutral party testing, but standardization may improve accuracy and reduce unnecessary colonoscopy.