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Objective: Longstanding subclinical Crohn's Disease (CD) can progress to complications such as intestinal strictures and penetrating (intestinal fistulae, abscesses, or perforations) disease. Despite the advances in non-invasive diagnostics for IBD, there is a dearth of biomarkers for predicting disease progression and complications in CD. Here, we investigate four baseline stool biomarkers, BDNF, MMP-8, TIMP-2, and Calprotectin (S100A8/A9), for their ability to predict disease progression in pediatric CD. Methods: Baseline stool samples from forty-seven patients recruited into the Pediatric RISK Stratification study were analyzed using an aptamer-based screening assay followed by validation by Enzyme-linked Immunosorbent Assays. Results: All four stool proteins were associated with disease activity at baseline. Baseline stool BDNF, MMP-8, and TIMP-2, but not Calprotectin distinguished progressors from non-progressors. Stool TIMP-2 predicted progression to stricturing and penetrating disease in CD, with higher levels predicting worse progression whereas an inverse relationship was seen with stool MMP-8, supporting the role of TIMP-2/MMP balance in driving fibrotic disease in CD. Indeed, stool TIMP-2 exhibited outstanding odds ratios of ~42 in predicting disease progression, outperforming all current protein or genetic markers of IBD. Stool BDNF was the next strongest performer associated with disease progression in CD. Conclusion: Stool TIMP-2 emerges as a novel predictor of disease progression in CD.
Polamarasetty et al. (Fri,) studied this question.