Preclinical Markers in Inflammatory Bowel Disease. A Nested Case–Control Study

Background Our objective was to determine if patients who later develop inflammatory bowel disease (IBD) show signs of increased inflammatory activity in plasma measured with high sensitivity C-reactive protein (CRP), calprotectin, and albumin before the clinical onset of IBD. Methods We identified 96 subjects who later developed IBD (70 ulcerative colitis [UC] and 26 Crohn’s disease [CD]). High sensitivity CRP, calprotectin, and albumin were analyzed in frozen plasma, donated from cases and sex–age matched controls 1–15 years before diagnosis. Results We found that subjects who later developed UC had lower albumin levels, and subjects who later developed CD had higher CRP levels than controls. Multivariable conditional logistic regression with albumin, calprotectin, and CRP showed a lower risk for developing IBD and UC with higher albumin levels (odds ratio [OR] 0.79, confidence interval [CI] 0.69–0.90; respective OR 0.77, CI 0.66–0.91). Higher CRP levels were associated with an increased risk of developing CD (OR 1.314, CI 1.060–1.630). When adjusting for body mass index or smoking in the logistic regression model, similar results were found. Plasma calprotectin levels in the preclinical period among patients with IBD did not differ from controls. Conclusions In this nested case–control study, subjects who later developed IBD had signs of low-grade systemic inflammation, indicated by significantly higher CRP plasma levels in CD and lower albumin plasma levels in UC, before the onset of clinical disease. Lay Summary This study shows that patients with inflammatory bowel disease have signs of inflammation in blood samples long before the disease becomes symptomatic. CRP was elevated in patients with Crohn’s disease and albumin was decreased in patients with ulcerative colitis. Graphical Abstract