title: Beyond Histological Remission: Intramucosal Calprotectin as a Potential Predictor of Outcomes in Ulcerative Colitis.
abstract: OBJECTIVE
  Histological remission and low faecal calprotectin are positive prognostic factors in ulcerative colitis [UC]. Intramucosal calprotectin [iMC], which can be readily determined by immunohistochemistry, has not so far been evaluated as a predictor of outcome in UC. We aimed to investigate the relationship between iMC and clinical, endoscopic, and histological measures of remission in UC, and the independent prognostic value of iMC.
  
  
  METHODS
  Ambulant patients with UC were recruited for a study comparing clinical activity indices. Sigmoidoscopy and biopsy were performed at the index visit. Clinical, endoscopic, and histological activity were scored and iMC semi-quantitatively measured using immunohistochemistry for the S100A8/9 heterodimer on colonic biopsies, scored as the mean number of positive cells in five high-power fields [HPF]. At the end of follow-up [6 years], data on steroid use, hospitalisation, and colectomy ['adverse outcomes'] were collected.
  
  
  RESULTS
  iMC was determined in 83 patients and 20 controls, and correlated with clinical, endoscopic, and histological activity [r = 0.51, 0.65, 0.53, p > 0.001, respectively]. iMC was lowest (median 2.4, interquartile range [IQR]: 5.2-5, p < 0.001) in patients with concordance between clinical, endoscopic, and histological remission. Median iMC > 5/HPF was associated with adverse outcome (hazard ratio [HR] 3.36, confidence interval [CI] 1.58, 7.15, p < 0.001). Only 53%, 33%, and 25% of patients in histological remission with iMC > 5 cells/HPF avoided an adverse outcome after 1, 3, and 6 years, respectively.
  
  
  CONCLUSIONS
  iMC was lowest in patients with concordant clinical, endoscopic, and histological remission. Median iMC > 5/HPF was associated with adverse outcomes despite histological remission. Therefore iMC is a potentially useful independent marker of activity.
authors.affiliation: Translational Gastroenterology Unit, Oxford University Hospital, Oxford, UK.
authors.forename: Marianne
authors.initials: M
authors.lastname: Guirgis
authors.affiliation: Translational Gastroenterology Unit, Oxford University Hospital, Oxford, UK.
authors.forename: Emily
authors.initials: E
authors.lastname: Wendt
authors.affiliation: Department of Cellular Pathology, Oxford University Hospital, Oxford, UK.
authors.forename: Lai Mun
authors.initials: LM
authors.lastname: Wang
authors.affiliation: Translational Gastroenterology Unit, Oxford University Hospital, Oxford, UK.
authors.forename: Alissa
authors.initials: A
authors.lastname: Walsh
authors.affiliation: Translational Gastroenterology Unit, Oxford University Hospital, Oxford, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Burger
authors.affiliation: Translational Gastroenterology Unit, Oxford University Hospital, Oxford, UK.
authors.forename: Robert V
authors.initials: RV
authors.lastname: Bryant
authors.affiliation: Translational Gastroenterology Unit, Oxford University Hospital, Oxford, UK.
authors.forename: Alex
authors.initials: A
authors.lastname: Kent
authors.affiliation: Translational Gastroenterology Unit, Oxford University Hospital, Oxford, UK.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Adamson
authors.affiliation: Translational Gastroenterology Unit, Oxford University Hospital, Oxford, UK.
authors.forename: Oliver
authors.initials: O
authors.lastname: Brain
authors.affiliation: Translational Gastroenterology Unit, Oxford University Hospital, Oxford, UK.
authors.forename: Simon P L
authors.initials: SPL
authors.lastname: Travis
authors.affiliation: Translational Gastroenterology Unit, Oxford University Hospital, Oxford, UK.
authors.forename: Satish
authors.initials: S
authors.lastname: Keshav
mesh_terms: D000328:Adult; D001706:Biopsy; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000473:pathology* / Q000628:therapy; D003106:Colon / Q000737:chemistry / Q000378:metabolism; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000737:chemistry* / Q000378:metabolism; D039841:Leukocyte L1 Antigen Complex / Q000032:analysis* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012074:Remission Induction; D012720:Severity of Illness Index; D012812:Sigmoidoscopy
chemical_list: D039841:Leukocyte L1 Antigen Complex
keywords: Mucosal calprotectin; predictors of outcome; remission