title: Faecal calprotectin, lactoferrin, M2-pyruvate kinase and S100A12 in severe ulcerative colitis: a prospective multicentre comparison of predicting outcomes and monitoring response.
abstract: OBJECTIVE
  To compare four faecal markers for their ability to predict steroid refractoriness in severe paediatric ulcerative colitis (UC). Construct validity and responsiveness to change were also assessed.
  
  
  METHODS
  This was a prospective multicentre cohort study. Stool samples from 101 children (13.3 + or - 3.6 years; Pediatric UC Activity Index (PUCAI) at admission 72 + or - 12 points) were obtained at the third day of intravenous steroid therapy. Repeated samples at discharge were obtained from 24 children. Predictive validity was assessed using diagnostic utility statistics to predict steroid failure (ie, the need for salvage treatment). Concurrent validity was assessed using correlational analysis with the following constructs: PUCAI, Lindgren and Seo scores, physician's global assessment, albumin, erythrocyte sedimentation rate and C-reactive protein (CRP). Responsiveness was assessed using test utility and correlational strategies.
  
  
  RESULTS
  Median values (IQR) were very high at baseline for all four markers (calprotectin 4215 microg/g (2297-8808); lactoferrin 212 microg/g (114-328); M2-pyruvate kinase (M2-PK) 363 U/g (119-3104); and S100A12 469 microg/g (193-1112)). M2-PK was numerically superior to the other three markers and CRP in predicting response to corticosteroid treatment (area under the receiver operating characteristic (ROC) curve 0.75 (95% CI 0.64 to 0.85; p<0.001) vs <0.65 for the others). However, it did not add to the predictive ability of the PUCAI (area under the ROC 0.81 (95% CI 0.73 to 0.89)). M2-PK also had the highest construct validity but with a modest mean correlation with all constructs (r=0.3; p<0.05). None of the markers was responsive to change (Spearman's rho correlation with change in the PUCAI <0.1; p>0.05, area under the ROC curve <0.65; p>0.05).
  
  
  CONCLUSIONS
  The four markers were greatly elevated in severe paediatric UC. Only M2-PK had good construct and predictive validity, and none was responsive to change. The PUCAI, a simple clinical index, performed better than the faecal markers in predicting outcome following a course of intravenous corticosteroids in severe UC.
authors.affiliation: Paediatric Gastroenterology and Nutrition Unit, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, POB 3235, Jerusalem 91031, Israel. turnerd@szmc.org.il
authors.forename: D
authors.initials: D
authors.lastname: Turner
authors.forename: S T
authors.initials: ST
authors.lastname: Leach
authors.forename: D
authors.initials: D
authors.lastname: Mack
authors.forename: K
authors.initials: K
authors.lastname: Uusoue
authors.forename: R
authors.initials: R
authors.lastname: McLernon
authors.forename: J
authors.initials: J
authors.lastname: Hyams
authors.forename: N
authors.initials: N
authors.lastname: Leleiko
authors.forename: T D
authors.initials: TD
authors.lastname: Walters
authors.forename: W
authors.initials: W
authors.lastname: Crandall
authors.forename: J
authors.initials: J
authors.lastname: Markowitz
authors.forename: A R
authors.initials: AR
authors.lastname: Otley
authors.forename: A M
authors.initials: AM
authors.lastname: Griffiths
authors.forename: A S
authors.initials: AS
authors.lastname: Day
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D003093:Colitis, Ulcerative / Q000175:diagnosis* / Q000188:drug therapy; D016903:Drug Monitoring / Q000379:methods; D004812:Epidemiologic Methods; D005243:Feces / Q000737:chemistry*; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007781:Lactoferrin / Q000378:metabolism; D039841:Leukocyte L1 Antigen Complex / Q000378:metabolism; D011379:Prognosis; D011770:Pyruvate Kinase / Q000378:metabolism; D009418:S100 Proteins / Q000378:metabolism; D000067616:S100A12 Protein; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D005938:Glucocorticoids; D039841:Leukocyte L1 Antigen Complex; D009418:S100 Proteins; D000067616:S100A12 Protein; C090441:S100A12 protein, human; D011770:Pyruvate Kinase; D007781:Lactoferrin