Polychronis Pavlidis1, Zakera Shums2, Andreas L Koutsoumpas3, Jay Milo4, Maria Papp5, Takeji Umemura6, Peter L Lakatos7, Daniel S Smyk8, Dimitrios P Bogdanos9, Alastair Forbes10, Gary L Norman11. 1. 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. 2. Inova Diagnostics, Inc., San Diego, CA 92131, USA. Electronic address: zshums@inovadx.com. 3. 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. 4. Inova Diagnostics, Inc., San Diego, CA 92131, USA. Electronic address: jmilo@inovadx.com. 5. 2nd Department of Medicine, University of Debrecen, Debrecen, Hungary. Electronic address: drpappm@yahoo.com. 6. Department of Medicine, Shinshu University, 3-1-1 Asahi, Matsumoto, Japan. Electronic address: tumemura@shihshu-u.ac.jp. 7. 1st Department of Medicine, Semmelweis University, Budapest, Hungary. Electronic address: kislakpet99@gmail.com. 8. 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. 9. 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. 10. Department of Gastroenterology and Clinical Nutrition, University College Hospital, 250 Euston Road, London NW1 2PG, UK. Electronic address: alastair.forbes@uea.ac.uk. 11. Inova Diagnostics, Inc., San Diego, CA 92131, USA. Electronic address: glnorman@inovadx.com.
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.
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: Konstantinos Gkiouras; Maria G Grammatikopoulou; Xenophon Theodoridis; Eirini Pagkalidou; Evangelia Chatzikyriakou; Anna G Apostolidou; Eirini I Rigopoulou; Lazaros I Sakkas; Dimitrios Petrou Bogdanos Journal: World J Gastroenterol Date: 2020-01-14 Impact factor: 5.742