Combined Serological IBD Markers Correlate with High Inflammatory Burden in a Large Cohort of Patients Presenting IBD-like Gastrointestinal Symptoms

Abstract

Purpose: Some patients with inflammatory bowel disease (IBD) will experience a benign clinical course. However, other patients face a progressive disease course, which can include high inflammatory burden, leading to a complicated disease that ultimately requires surgery. Several studies have shown that early aggressive therapy can benefit patients with aggressive disease. It is also established that both the presence and magnitude of serological markers are correlated with specific phenotypes and with the need for intestinal surgery. The aim of this study was to investigate the relationship between serological markers and inflammatory burden in patients with a suspected diagnosis of IBD. Methods: Marker data from 43,679 de-identified patients between ages 2 and 85 years old were collected from Prometheus Labs CLIA laboratory. The patient diagnosis was unknown. The prevalence of serological markers (ASCA-A, ASCA-G, ANCA, pANCA, and anti-OmpC), anti-flagellins (CBir1, A4-Fla2 & FlaX), and inflammatory markers (CRP, SAA, ICAM, VCAM, and VEGF) were compared. Quartile Sum Scores (QSS) were calculated from serological markers by assigning a score from 0-3 for each marker based on the quartile; the marker value was followed by summation of these per-marker scores. Inflammatory markers were combined to form an inflammatory index by centering their values at the reference range for each assay, scaling each marker, then summing them on a per-patient basis. Results: QSS values combining the eight serologic markers ranged from 0 to 19. High QSS score above >=16 or >=17 represented 22.4% and 11.5% of the population, respectively. Higher QSS was correlated with an increased acute inflammation as assessed by CRP. High CRP prevalence increased from 66.7%, to 71.8%, to 77.5% in individuals presenting QSS =17, =18 and =19, respectively. When the ASCA markers were removed from the QSS calculation (QSS range 0 to 13 for combining the remaining six markers), the top two QSS values, >=12 and >=13, still correlated with a high CRP prevalence of 64.2% and 70.2%, respectively. Similarly, the higher QSS correlated with higher inflammatory indices. High inflammatory index prevalence increased from 28.1%, 33.3%, to 41.6% in individuals presenting QSS =17, =18 and =19, respectively. Conclusion: In this large cohort of patients presenting IBD-like gastrointestinal symptoms, we observed a relationship between serological value (QSS) with both acute inflammation and high inflammatory index score. These results demonstrated the benefit of a multi-marker diagnostic panel for detecting those patients with high chance of developing aggressive disease. Our results also showed the minimal contribution of ASCA in the QSS correlation with inflammation. Disclosure - Fred Princen, Steven Lockton, Jordan Stachelski, Cheryl Triggs, Michelle Brown and Sharat Singh - Employees of Prometheus Labs, Inc.