San Diego—A new diagnostic test incorporating 17 serologic, genetic and inflammatory markers is 87% accurate in identifying inflammatory bowel disease (IBD) and 93% accurate in differentiating ulcerative colitis (UC) from Crohn’s disease (CD), according to research presented at the 2012 Digestive Disease Week (DDW) meeting.
Marla Dubinsky, MD, director of the Pediatric Inflammatory Bowel Disease Center at Cedars-Sinai Medical Center in Los Angeles, believes the tool can be used when a definitive IBD, CD or UC diagnosis remains hazy, despite clinical, endoscopic and histologic findings.
“The serologies, in particular, add additional information in cases of diagnostic uncertainty,” said Dr. Dubinsky, who was not involved in the development of the instrument.
Prometheus launched the new test as an improvement on IBD Serology 7, which measures serologic levels of several antibodies associated with both CD and UC, including anti-Saccharomyces cerevisiae(ASCA), perinuclear antineutrophil cytoplasmic antibodies (pANCA), antibody to outer membrane porin C (anti-OmpC) and anti-CBir1 flagellin (anti-CBir1). IBD Serology 7 also included a diagnostic algorithm to help interpret the findings.
According to a Prometheus representative, the sensitivity and specificity of the IBD Serology 7 suffered from its reliance on serology markers alone and from low sensitivities of ASCA in CD and ANCA in UC. In contrast, the new test measures the presence of serologic markers included in the Serology 7, as well as two additional markers, anti-Fla-X, anti-A4 Fla2. Prometheus says the addition of these two markers may help identify subsets of patients that could have been missed otherwise.
The new instrument also tests for genetic markers—including ATG16L1NKX2.3STAT3 and ECM1—that are linked to defective bacterial handling or autophagy, dysregulated signaling pathways and impaired epithelial barrier function in IBD. The tool also tests for several inflammatory markers, including intercellular adhesion molecule 1, vascular cell adhesion molecule 1, vascular endothelial growth factor, C-reactive protein and serum amyloid A. Additionally, the tool includes an integrated algorithm, which interprets the relationships between the serologic, genetic and inflammatory findings and provides an initial prediction of IBD and a subsequent differential diagnosis of UC or CD.
Scott Plevy, MD, associate professor of medicine in the Division of Gastroenterology and Hepatology at the University of North Carolina at Chapel Hill’s School of Medicine, and colleagues presented findings of the Prometheus-funded study of the tool at the DDW meeting (abstract 166). The trial included 437 well-characterized IBD and non-IBD patients.
According to Dr. Plevy, the test demonstrated sensitivity rates of 74% in predicting IBD, 89% in identifying CD and 98% in recognizing UC. Corresponding specificity rates were 90%, 81% and 84% for IBD, CD and UC, respectively. Overall, the test was 87% accurate in distinguishing IBD from non-IBD and 93% accurate in distinguishing UC from CD, he reported.
“The [assay] represents an innovative approach in biomarker development, incorporating current advances in pathophysiology with state-of-the-art biostatistical analysis,” Dr. Plevy said. “As we further refine and redefine the tremendous clinical heterogeneity that we refer to as CD and UC, such approaches will grow in importance as adjuncts to clinical diagnosis.”
According to Dr. Dubinsky, one potential application of the test would be to help clinicians who are considering a referral for colectomy to determine more confidently whether the patient has a “CD-like” or “UC-like” phenotype.
“The genetic markers are interesting but need to be interpreted with caution, since these genes may be present in both UC and CD, as newer genetic association studies are demonstrating,” she said. Further work needs to be done to identify completely nonoverlapping genes and thereby improve on instruments like [this one].”
Ellen Scherl, MD, director of the Jill Roberts Center for Inflammatory Bowel Disease in the Division of Gastroenterology and Hepatology at Weill Cornell Medical College and NewYork-Presbyterian Hospital, in New York City, explained that some test findings are prognostic of disease activity and therefore can help clinicians select more appropriate treatments.
“High ASCA-IgG and ASCA-IgA titers in Crohn’s disease patients have been found to predict strictures, so you might want to follow a more aggressive treatment path in patients with these findings,” Dr. Scherl told Gastroenterology & Endoscopy News. “As we enter the era of personalized medicine, we’ll find these diagnostics more and more helpful in helping us select the most effective therapies.”
Dr. Scherl cautioned against using the tool for initial patient screening, saying that colonoscopy remains the gold standard.