P-014 Circulating C-Reactive Protein and Interleukin-6 and Risk of Inflammatory Bowel Disease. (March 2016)

• Record Type: Journal Article
• Authors: Lochhead, Paul; Khalili, Hamed; Ananthakrishnan, Ashwin; Richter, James; Chan, Andrew
• Is Part Of: Inflammatory bowel diseases. Volume 22(2016:Mar.)Supplement 1
• Publication Date: 2016-03
• Subjects: Inflammatory bowel diseases -- Periodicals; Colitis, Ulcerative -- Periodicals; Crohn Disease -- Periodicals; Inflammatory Bowel Diseases -- Periodicals; 616.344
• DOI: 10.1097/01.MIB.0000480060.34687.ed
• Languages: English
• ISSNs: 1078-0998

Abstract

Abstract : Background: Evidence from serologic marker studies suggests that immune dysfunction may precede symptoms of inflammatory bowel disease (IBD) by several years. Characterizing pre-clinical systemic inflammation could help elucidate the timing of environmental influences relative to the onset of symptomatic IBD. We therefore set out to evaluate associations between circulating pre-diagnostic levels of inflammatory markers and risk of incident Crohn's disease (CD) and ulcerative colitis (UC). Methods: We conducted a nested case–control study of participants enrolled in 2 population-based, nationwide, prospective cohort studies, the Nurses' Health Study and the Nurses' Health Study II. Eighty-three cases of CD and 90 cases of UC with available pre-diagnostic blood specimens were matched to 344 controls. Pre-diagnostic plasma levels of high-sensitivity CRP (hsCRP) and interleukin-6 (IL6) were determined. We investigated associations between each inflammatory marker and IBD risk using multivariable logistic regression models to adjust for potential confounding exposures including smoking, oral contraceptive use, physical activity, and body mass index. Results: The median time interval between blood collection and diagnosis of CD or UC was 6.8 years (range, 1 month to 20.4 years). Compared to the lowest quintile of pre-diagnostic IL6, the highest quintile was associated with an odds ratio (OR) of 4.68 (95% confidence interval [CI], 1.91–11.46) for CD ( P trend < 0.001), and an OR of 3.43 (95% CI, 1.44–8.15) for UC ( P trend = 0.004). For pre-diagnostic hsCRP, compared to the lowest quintile, the highest quintile was associated with an OR of 2.82 (95% CI, 1.15–6.87) for CD ( P trend = 0.019), and an OR of 1.79 (95% CI, 0.80–3.99) for UC ( P trend = 0.015). Since the observed associations may have been driven by undiagnosed symptomatic IBD at the time of blood collection, we performed sensitivity analyses excluding cases of CD or UC diagnosed within 2 years of blood collection. Effect estimates for the risk of CD and UC in relation to IL6 were broadly similar to those of our main analysis (both P trend ⩽ 0.01). For hsCRP, a statistically significant association remained across increasing quintiles in relation to CD risk ( P trend = 0.026); however, the association with UC risk was attenuated ( P trend = 0.067). In stratified analyses, we found no evidence that time interval between blood collection and diagnosis modified the associations between IL6 or hsCRP and IBD risk (all P interaction ≥ 0.49). Conclusions: Pre-diagnostic levels of plasma CRP and IL6 are associated with risk of CD and UC. Although the biologic mechanisms underlying these observations require elucidation, our data suggest that subclinical levels of systemic inflammation are a feature of an early, or pre-disease state, which precedes the development of symptomatic IBD by several years. Our data can help contribute to our understanding of the natural history of IBD, and have additional implications for the timing of exposure assessment in epidemiologic studies of IBD.