title: Diagnostic and clinical significance of Crohn's disease-specific anti-MZGP2 pancreatic antibodies by a novel ELISA.
abstract: BACKGROUND
  We developed a new IgA and IgG anti-MZGP2 antibody ELISAs based on recombinant isoform-4 of human zymogen granule protein-2 (GP2), which is the major autoantigen of Crohn's disease (CrD)-specific pancreatic autoantibodies and assessed their clinical relevance in the largest inflammatory bowel disease (IBD) cohort tested to date.
  
  
  METHODS
  832 sera were studied, including 617 consecutive IBD patients from 323 CrD and 294 ulcerative colitis (UC) follow-up in a tertiary centre, and 112 pathological and 103 normal controls.
  
  
  RESULTS
  Sensitivity of IgA anti-MZGP2 for CrD in the IBD population was 15% and specificity was 98% (95, 99), while the sensitivity and specificity of IgG anti-MZGP2 were 27% and 97%. IgA and IgG anti-MZGP2 combined testing led to a sensitivity of 31% and a specificity of 96%. Positivity for either ASCA (IgA or IgG) or anti-MZGP2 (IgA or IgG) showed a sensitivity of 75% (70, 80) and a specificity of 84% (79, 89). IgA anti-MZGP2 antibodies were more prevalent in CrD patients with early disease onset (p=0.011). Also, anti-MZGP2 positive patients more frequently had extensive disease with ileal involvement. Patients with longer disease duration were more likely to have IgG anti-MZGP2 antibodies.
  
  
  CONCLUSIONS
  Our novel ELISA confirms the high specificity of anti-MZGP2 antibodies for CrD and their association with disease severity phenotypes.
authors.affiliation: Division of Transplantation Immunology and Mucosal Biology, King's College London School of Medicine at King's College Hospital, Denmark Hill Campus, London SE5 9RJ, UK; Department of Gastroenterology and Clinical Nutrition, University College Hospital, 250 Euston Road, London NW1 2PG, UK. Electronic address: polpavlid@gmail.com.
authors.forename: Polychronis
authors.initials: P
authors.lastname: Pavlidis
authors.affiliation: Inova Diagnostics, Inc., San Diego, CA 92131, USA. Electronic address: zshums@inovadx.com.
authors.forename: Zakera
authors.initials: Z
authors.lastname: Shums
authors.affiliation: Division of Transplantation Immunology and Mucosal Biology, King's College London School of Medicine at King's College Hospital, Denmark Hill Campus, London SE5 9RJ, UK; Department of Gastroenterology and Clinical Nutrition, University College Hospital, 250 Euston Road, London NW1 2PG, UK. Electronic address: andreas_livadia@hotmail.com.
authors.forename: Andreas L
authors.initials: AL
authors.lastname: Koutsoumpas
authors.affiliation: Inova Diagnostics, Inc., San Diego, CA 92131, USA. Electronic address: jmilo@inovadx.com.
authors.forename: Jay
authors.initials: J
authors.lastname: Milo
authors.affiliation: 2nd Department of Medicine, University of Debrecen, Debrecen, Hungary. Electronic address: drpappm@yahoo.com.
authors.forename: Maria
authors.initials: M
authors.lastname: Papp
authors.affiliation: Department of Medicine, Shinshu University, 3-1-1 Asahi, Matsumoto, Japan. Electronic address: tumemura@shihshu-u.ac.jp.
authors.forename: Takeji
authors.initials: T
authors.lastname: Umemura
authors.affiliation: 1st Department of Medicine, Semmelweis University, Budapest, Hungary. Electronic address: kislakpet99@gmail.com.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Lakatos
authors.affiliation: Division of Transplantation Immunology and Mucosal Biology, King's College London School of Medicine at King's College Hospital, Denmark Hill Campus, London SE5 9RJ, UK. Electronic address: daniel.s.smyk@gmail.com.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Smyk
authors.affiliation: Division of Transplantation Immunology and Mucosal Biology, King's College London School of Medicine at King's College Hospital, Denmark Hill Campus, London SE5 9RJ, UK; 1st Department of Medicine, Semmelweis University, Budapest, Hungary; Department of Medicine, School of Health Sciences, University of Thessaly, Larissa 40500, Greece. Electronic address: bogdanos@med.uth.gr.
authors.forename: Dimitrios P
authors.initials: DP
authors.lastname: Bogdanos
authors.affiliation: Department of Gastroenterology and Clinical Nutrition, University College Hospital, 250 Euston Road, London NW1 2PG, UK. Electronic address: alastair.forbes@uea.ac.uk.
authors.forename: Alastair
authors.initials: A
authors.lastname: Forbes
authors.affiliation: Inova Diagnostics, Inc., San Diego, CA 92131, USA. Electronic address: glnorman@inovadx.com.
authors.forename: Gary L
authors.initials: GL
authors.lastname: Norman
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000276:immunology*; D003093:Colitis, Ulcerative / Q000175:diagnosis / Q000276:immunology; D003424:Crohn Disease / Q000175:diagnosis* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D005260:Female; D058851:GPI-Linked Proteins / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000276:immunology*
chemical_list: D001323:Autoantibodies; C489339:GP2 protein, human; D058851:GPI-Linked Proteins
keywords: Autoantibody; Bowel disease; Marker; Sensitivity; Specificity