title: Serological markers associated with disease behavior and response to anti-tumor necrosis factor therapy in ulcerative colitis.
abstract: OBJECTIVE
  Information is limited on the relationship between serological markers and disease behavior and anti-tumor necrosis factor-α (anti-TNF) therapy response in ulcerative colitis (UC). This study aimed to determine the association between serological markers and unfavorable UC behavior defined as need for colectomy or UC-related hospitalization. The association between serological markers and requirement for and outcome of anti-TNF therapy was also evaluated.
  
  
  METHODS
  Two hundred thirty patients were studied. Requirement for colectomy, UC-related hospitalization, and anti-TNF therapy were documented. Response to anti-TNF therapy at 1 year and rates of therapy discontinuation were recorded. Titers of perinuclear anti-neutrophil cytoplasmic antibodies (pANCAs), anti-Saccharomyces cerevisiae antibody (ASCA), and antibody to Escherichia Coli outer membrane porin (anti-OmpC) were determined. Antibody reference ranges were used to dichotomize subjects into seropositive and seronegative groups. Where multiple tests were performed, P-values were Bonferroni corrected (pcorr).
  
  
  RESULTS
  Extensive colitis was associated with requirement for colectomy and UC-related hospitalization, HR 7.7 (95% confidence interval [CI] 1.9-32.2) pcorr  = 0.03 and HR 2.7 (95% CI 1.5-4.6), pcorr  = 0.006, respectively. No serological variable was associated with unfavorable UC behavior. Anti-OmpC positivity was associated with a lack of response to anti-TNF therapy at 1 year (odds ratio 0.14 [95% CI 0.03-0.60], pcorr  = 0.04) and increased likelihood of therapy discontinuation (HR 2.2 [95% CI 1.1-4.7], P = 0.03).
  
  
  CONCLUSIONS
  Extensive colitis is associated with unfavorable disease course in UC. Anti-OmpC holds promise as a biomarker of anti-TNF therapy response in UC; however, prospective studies are required before it can be incorporated into routine clinical practice.
authors.affiliation: Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Canada; Division of Gastroenterology, Department of Medicine, University of Toronto, Toronto, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Kevans
authors.forename: Matti
authors.initials: M
authors.lastname: Waterman
authors.forename: Raquel
authors.initials: R
authors.lastname: Milgrom
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.forename: Gert
authors.initials: G
authors.lastname: Van Assche
authors.forename: Mark
authors.initials: M
authors.lastname: Silverberg
mesh_terms: D000293:Adolescent; D000328:Adult; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood*; D000907:Antibodies, Bacterial / Q000097:blood; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000494:pharmacology; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D002648:Child; D003093:Colitis, Ulcerative / Q000175:diagnosis* / Q000188:drug therapy*; D029968:Escherichia coli Proteins / Q000276:immunology; D005260:Female; D005765:Gastrointestinal Agents / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D018272:Porins / Q000276:immunology; D012441:Saccharomyces cerevisiae / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D055815:Young Adult
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D001425:Bacterial Outer Membrane Proteins; D015415:Biomarkers; D029968:Escherichia coli Proteins; D005765:Gastrointestinal Agents; C114347:OmpG protein, E coli; D018272:Porins; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab
keywords: ASCA; UC; anti-OmpC; anti-TNF therapy; pANCA