title: Rediscovery of the Anti-Pancreatic Antibodies and Evaluation of their Prognostic Value in a Prospective Clinical Cohort of Crohn's Patients: The Importance of Specific Target Antigens [GP2 and CUZD1].
abstract: BACKGROUND
  Glycoprotein 2[GP2] and CUB zona pellucida-like domain 1[CUZD1] belong to protein families involved in gut innate immunity processes and have recently been identified as specific targets of anti-pancreatic autoantibodies [PAbs] in Crohn's disease[CD]. We aimed to determine the prognostic potential of novel target-specific PAbs regarding long-term disease course of an adult CD patient cohort.
  
  
  METHODS
  Sera of 458 consecutive well-characterised IBD patients from a single referral IBD centre were tested by enzyme-linked immunosorbent assay [ELISA] with isoform 4 of recombinant GP2 [anti-MZGP2 and anti-GP2 IgA/IgG] and indirect immunofluorescence test [IIFT] system with GP2 and CUZD1 expressing transfected HEK 293 cells [anti-rPAg2 and rPAg1 IgA/IgG]. Clinical data were available on complicated disease or surgical interventions as well as disease activity and medical treatment during the prospective follow-up [median, 108 months].
  
  
  RESULTS
  Totals of 12.4% and 20.8% of CD patients were positive for IgA/IgG type of anti-GP2 and anti-CUZD1, respectively, with a significant difference compared with UC [p < 0.01]. Antibody status was stable over time. Agreement among three different anti-GP2 assays was good. Positivity for PAbs, mainly IgA subtypes, predicted a faster progression towards complicated disease course. In Kaplan-Meier analysis, time to surgery or development of perianal disease was associated with anti-GP2 IgA [pLogRank < 0.01] or anti-CUZD1 IgA [pLogRank < 0.001] positivity, respectively. Anti-CUZD1 IgA remained an independent predictor in the multivariate Cox-regression model (hazard ratio [HR]: 3.43, 95% confidence interval [CI]: 1.68-7.02, p < 0.001).
  
  
  CONCLUSIONS
  The present study has shown that specific PAbs [especially IgA subtype] predict complicated disease course including the development of perianal disease in CD.
authors.affiliation: Division of Gastroenterology, Department of Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Maria
authors.initials: M
authors.lastname: Papp
authors.affiliation: Division of Gastroenterology, Department of Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Nora
authors.initials: N
authors.lastname: Sipeki
authors.affiliation: Division of Gastroenterology, Department of Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Tamas
authors.initials: T
authors.lastname: Tornai
authors.affiliation: Division of Gastroenterology, Department of Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Istvan
authors.initials: I
authors.lastname: Altorjay
authors.affiliation: Inova Diagnostics, San Diego, CA, USA.
authors.forename: Gary L
authors.initials: GL
authors.lastname: Norman
authors.affiliation: Inova Diagnostics, San Diego, CA, USA.
authors.forename: Zakera
authors.initials: Z
authors.lastname: Shums
authors.affiliation: Faculty of Natural Sciences, Brandenburg University of Technology Cottbus-Senftenberg, Senftenberg, Germany GA Generic Assays GmbH, Dahlewitz, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Roggenbuck
authors.affiliation: Institute of Experimental Immunology, Euroimmun AG, Luebeck, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Fechner
authors.affiliation: Institute of Experimental Immunology, Euroimmun AG, Luebeck, Germany.
authors.forename: Winfried
authors.initials: W
authors.lastname: Stöcker
authors.affiliation: Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Peter
authors.initials: P
authors.lastname: Antal-Szalmas
authors.affiliation: 1st Department of Pediatrics, Semmelweis University, Budapest, Hungary.
authors.forename: Gabor
authors.initials: G
authors.lastname: Veres
authors.affiliation: 1st Department of Pediatrics, Semmelweis University, Budapest, Hungary.
authors.forename: Peter Laszlo
authors.initials: PL
authors.lastname: Lakatos
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D003424:Crohn Disease / Q000097:blood / Q000175:diagnosis* / Q000276:immunology / Q000628:therapy; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005500:Follow-Up Studies; D058851:GPI-Linked Proteins / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D053208:Kaplan-Meier Estimate; D008297:Male; D008565:Membrane Proteins / Q000276:immunology*; D010179:Pancreas / Q000276:immunology*; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012720:Severity of Illness Index
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; C488236:CUZD1 protein, human; C489339:GP2 protein, human; D058851:GPI-Linked Proteins; D008565:Membrane Proteins
keywords: Crohn’s disease; Serological antibodies; anti-pancreatic antibodies; disease progression; glycoprotein 2; glycoprotein CUZD1; immunoglobulin A; ulcerative colitis