Diagnostic and clinical significance of Crohn’s disease-specific anti-MZGP2 pancreatic antibodies by a novel ELISA: New anti-MZGP2 ELISA in Crohn’s

Pavlidis, Polychronis, Shums, Zakera, Koutsoumpas, Andreas L., Milo, Jay, Papp, Maria, Uemurea, Takeji, Smyk, Daniel S., Bogdanos, Dimitrios P., Forbes, Alastair ORCID: https://orcid.org/0000-0001-7416-9843 and Norman, Gary L. (2015) Diagnostic and clinical significance of Crohn’s disease-specific anti-MZGP2 pancreatic antibodies by a novel ELISA: New anti-MZGP2 ELISA in Crohn’s. Clinica Chimica Acta, 441. 176–181. ISSN 0009-8981

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Abstract

The recent identification of the pancreas major zymogen granule membrane glycoprotein 2 (MZGP2) as the major autoantigen of pancreatic autoantibody (PAB) has led to the appreciation of anti-MZGP2 antibodies as specific markers of Crohn’s disease (CrD). We have recently developed new, robust, highly sensitive and specific IgA and IgG anti-MZGP2 antibody ELISAs and assessed their clinical relevance in the largest inflammatory bowel disease (IBD) cohort tested to date for anti-MZGP2 antibodies. In contrast to currently available anti-MZGP2 ELISAs, the new QUANTA Lite® MZGP2 ELISA (INOVA Diagnostics, San Diego, CA) utilizes the eukaryotically-expressed specific isoform 4 of human GP2 UniProtKB: P55259. A total of 832 sera were studied including 617 consecutive IBD patients (323 CrD and 294 UC) under regular follow-up in a tertiary centre, 112 patients with various diseases, and 103 healthy blood donors. The new ELISA’s calculated AUC was 0.5968, 95% CI (0.5552, 0.6383) for IgA anti-MZGP2 [CD vs non-CD (UC plus controls)] and 0.6236, 95% CI (0.5813, 0.6659) for IgG anti-MZGP2. The sensitivity of IgA anti-MZGP2 for CrD in the IBD population was 15% and the specificity was 98% (95, 99), while the sensitivity and specificity of IgG anti-MZGP2 was 27% and 97%. IgA and IgG anti-MZGP2 combined testing led to a sensitivity of 31% and specificity of 96%. Positivity for either ASCA (IgA or IgG) or anti-MZGP2 (IgA or IgG) showed a sensitivity of 75% (70, 80) and specificity of 84% (79, 89). Of clinical relevance, IgA anti- MZGP2 antibodies were more prevalent in patients with early disease onset (Montreal classification A1, p=0.011), while patients with localised colonic disease were less likely to be IgG anti-MZGP2 positive. Anti-MZGP2 positive patients more frequently had extensive disease with ileal involvement and stricture formation. Patients with longer disease duration were more likely to have IgG anti-MZGP2 or IgA ASCA antibodies. In conclusion, the new IgA and IgG anti-MZGP2 antibody ELISAs allow accurate autoantibody determination, and can be used as a tool to study the clinical significance and utility of these autoantibodies in patients with IBD.

Item Type:	Article
Uncontrolled Keywords:	autoantibody,intestine,marker,sensitivity,specificity,sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology Faculty of Medicine and Health Sciences > Research Groups > Nutrition and Preventive Medicine
Depositing User:	Pure Connector
Date Deposited:	02 Jan 2015 11:30
Last Modified:	17 Oct 2022 13:30
URI:	https://ueaeprints.uea.ac.uk/id/eprint/51474
DOI:	10.1016/j.cca.2014.12.010

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