Role of HMGB1 as a suitable biomarker of subclinical intestinal inflammation and mucosal healing in patients with inflammatory bowel disease

Francesca Palone, Roberta Vitali, Salvatore Cucchiara, Maria Pierdomenico, Anna Negroni, Marina Aloi, Federica Nuti, Carla Felice, Alessandro Armuzzi, Laura Stronati

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Abstract

Background: Noninvasive biomarkers of high- and low-grade intestinal inflammation and of mucosal healing (MH) in patients with inflammatory bowel disease are currently lacking. We have recently shown that fecal high mobility group box 1 (HMGB1) protein is a novel biomarker of gut inflammation. We aimed at investigating in a mouse model if HMGB1 was able to foresee both a clinically evident and a subclinical gut inflammation and if its normalization indicated MH. We also aimed at confirming the results in patients with Crohn's disease (CD) and ulcerative colitis. Methods: C57BL6/J mice were treated with increasing doses of dextran sodium sulphate to induce colitis of different severity degrees; 28 with CD, 23 with ulcerative colitis, and 17 controls were also enrolled. Fecal HMGB1 was analyzed by enzyme-linked immunosorbent assay and immunoblotting. Results: Fecal HMGB1 increased by 5-, 11-, 18-, and 24-folds with dextran sodium sulphate doses of 0.25%, 0.50%, 1%, and 4%, respectively, showing that the protein detected a high-grade and a subclinical inflammation. After a recovery time of 4-week posttreatment, HMGB1 returned to control levels, paralleling MH. In patients, fecal HMGB1 significantly correlated with endoscopic indexes (Simple Endoscopic Score for Crohn's Disease [SES-CD], endoscopic Mayo subscore), but not with the disease activity indexes (Crohn's disease Activity Index, partial Mayo score). Conclusions: Fecal HMGB1 is a robust noninvasive biomarker of clinically overt and subclinical gut inflammation; it can also be a surrogate marker of MH. We suggest the use of fecal HMGB1 to monitor the disease course and assess therapy outcomes in inflammatory bowel disease. Copyright © 2014 Crohn's & Colitis Foundation of America, Inc.
Original languageEnglish
Pages (from-to)1448 - 1457
Number of pages10
JournalInflammatory Bowel Diseases
Volume20
Issue number8
DOIs
Publication statusPublished - 2014
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Gastroenterology

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