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

TitoloRole of HMGB1 as a suitable biomarker of subclinical intestinal inflammation and mucosal healing in patients with inflammatory bowel disease
Tipo di pubblicazioneArticolo su Rivista peer-reviewed
Anno di Pubblicazione2014
AutoriPalone, Francesca, Vitali Roberta, Cucchiara S., Pierdomenico Maria, Negroni Anna, Aloi M., Nuti F., Felice C., Armuzzi A., and Stronati L.
RivistaInflammatory Bowel Diseases
Volume20
Paginazione1448-1457
ISSN10780998
Parole chiaveadult, aged, animal, animal experiment, animal model, animal tissue, Animals, article, biological marker, Biological Markers, Blotting, C57BL mouse, case control study, Case-Control Studies, cell culture, Cells, chemically induced, chemistry, colitis, comparative study, complication, controlled study, Crohn disease, Cultured, dextran sodium sulfate-induced colitis, Dextran Sulfate, disease activity, disease course, Disease Progression, double blind procedure, Double-Blind Method, enteritis, enzyme linked immunosorbent assay, Enzyme-Linked Immunosorbent Assay, feces, Female, follow up, Follow-Up Studies, genetics, healing, high mobility group B1 protein, HMGB1 Protein, human, Humans, Immunoblotting, Inbred C57BL, inflammation, inflammatory bowel disease, Intestinal Mucosa, intestine mucosa, major clinical study, male, Messenger, messenger RNA, metabolism, Mice, Middle Aged, mouse, nonhuman, peroxidase, physiology, priority journal, prognosis, real time polymerase chain reaction, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, reverse transcription polymerase chain reaction, RNA, Simple Endoscopic Score for Crohn's Disease, Ulcerative, ulcerative colitis, very elderly, Western, Western blotting, wound healing, young adult
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.

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URLhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-84905446363&doi=10.1097%2fMIB.0000000000000113&partnerID=40&md5=bd3f207ed35e9cabee33170a4b855493
DOI10.1097/MIB.0000000000000113
Citation KeyPalone20141448