title: Role of HMGB1 as a suitable biomarker of subclinical intestinal inflammation and mucosal healing in patients with inflammatory bowel disease.
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.
authors.affiliation: *Department of Radiobiology and Human Health, ENEA, Rome, Italy; †Department of Pediatrics and Infantile Neuropsychiatry, Pediatric Gastroenterology and Liver Unit, Sapienza University of Rome, Rome, Italy; and ‡IBD Unit, Complesso Integrato Columbus, Catholic University, Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Palone
authors.forename: Roberta
authors.initials: R
authors.lastname: Vitali
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cucchiara
authors.forename: Maria
authors.initials: M
authors.lastname: Pierdomenico
authors.forename: Anna
authors.initials: A
authors.lastname: Negroni
authors.forename: Marina
authors.initials: M
authors.lastname: Aloi
authors.forename: Federica
authors.initials: F
authors.lastname: Nuti
authors.forename: Carla
authors.initials: C
authors.lastname: Felice
authors.forename: Alessandro
authors.initials: A
authors.lastname: Armuzzi
authors.forename: Laura
authors.initials: L
authors.lastname: Stronati
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000032:analysis*; D015153:Blotting, Western; D016022:Case-Control Studies; D002478:Cells, Cultured; D003092:Colitis / Q000139:chemically induced / Q000150:complications / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000150:complications / Q000175:diagnosis* / Q000378:metabolism; D003424:Crohn Disease / Q000150:complications / Q000175:diagnosis* / Q000378:metabolism; D016264:Dextran Sulfate / Q000633:toxicity; D018450:Disease Progression; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005243:Feces / Q000737:chemistry; D005260:Female; D005500:Follow-Up Studies; D024243:HMGB1 Protein / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism; D007413:Intestinal Mucosa / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009195:Peroxidase / Q000378:metabolism; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014945:Wound Healing; D055815:Young Adult
chemical_list: D015415:Biomarkers; D024243:HMGB1 Protein; D012333:RNA, Messenger; D016264:Dextran Sulfate; D009195:Peroxidase