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P313. A composite serological panel predicts burden of inflammation in Crohn's disease

O. Ben-Bassat1, S. Lockton2, F. Princen2, J.M. Stempak3, G. Van Assche1, S. Singh2, M.S. Silverberg1, 1Mount Sinai Hospital, Gastroenterology, Toronto, Canada, 2Prometheus Labs, San Diego, United States, 3Mount Sinai Hospital, Zane Cohen Centre for Digestive Diseases, Toronto, Canada

Background

There remains a void in identifying biomarkers that can be used to measure the burden of inflammation in inflammatory bowel disease (IBD). Advances in therapeutic approaches suggest that mucosal healing is the ideal goal, however, currently endoscopic evaluation is the only accurate way to monitor this. CRP and fecal calprotectin have some utility but also several flaws. A multi-marker diagnostic panel containing inflammatory markers and serum antibodies was therefore examined to determine its potential utility as a measure of burden of inflammation.

Methods

174 patients with Crohn's disease (CD) were evaluated with serological markers (ASCA-A and G, ANCA, pANCA, anti-OmpC, CBir1, A4-Fla2 and FlaX) and inflammatory markers (CRP, SAA, ICAM, VCAM, and VEGF) (Prometheus Laboratories, San Diego, CA). All had endoscopic assessment within 1 year of serum collection. Endoscopy reports were scored according to severity and disease extent and location. Analysis of variance (ANOVA) tests were applied to individual markers, and further location-specific marker patterns were analyzed to create a “marker signature” for each location and severity. An inflammatory index score was created by first entering each inflammatory marker to their respective reference range and, per subject, calculating the score as follows: (CRP + SAA)/2 + (ICAM + VCAM)/2 + VEGF.

Results

The inflammatory index was significantly and positively associated with CD severity (p = 5.5×10−6). This index was independent of disease location (p = 0.335). 3 markers were significantly associated with increasing severity: CRP (p = 1.3×10−7), SAA (p = 8.8×10−5) & VEGF (p = 0.044). Similarly, five serological markers were associated with severity: ASCA-A (p = 0.021), ANCA (p = 0.041), CBir1 (p = 0.012), A4-Fla2 (p = 0.013) & FlaX (0.019). Colonic involvement was associated with higher VEGF (p = 0.0046) and CRP (p = 0.04), suggesting increased systemic inflammation. Disease location was also significantly associated with higher titres of ASCA-A (p = 0.001), ASCA-G (p = 0.004), Fla2 (p = 0.042) and FlaX (p = 0.021). There was a trend towards higher flagellin titres in left colonic CD.

Conclusion

In this cohort, we demonstrated a significant correlation between CD disease severity, assessed endoscopically, with an inflammatory index score based on a panel of serum inflammatory markers. Furthermore, each disease location exhibited a unique serological marker pattern. This multi-marker diagnostic panel may be a useful instrument to assessing the burden of endoscopic disease severity in CD.