{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:50:38Z","timestamp":1790805038077,"version":"4.1.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100011684","name":"Crohn's and Colitis Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011684","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Longstanding subclinical Crohn\u2019s 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Stool TIMP-2 emerges as a novel predictor of disease progression in CD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1624045","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T06:06:47Z","timestamp":1775801207000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Baseline stool TIMP-2 predicts strictures and penetrating disease progression in Crohn\u2019s patients"],"prefix":"10.3389","volume":"17","author":[{"given":"Harshavardhan","family":"Polamarasetty","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, University of Houston","place":["Houston, TX, United 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