Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 14, 2020; 26(2): 246-265
Published online Jan 14, 2020. doi: 10.3748/wjg.v26.i2.246
Diagnostic and clinical significance of antigen-specific pancreatic antibodies in inflammatory bowel diseases: A meta-analysis
Konstantinos Gkiouras, Maria G Grammatikopoulou, Xenophon Theodoridis, Eirini Pagkalidou, Evangelia Chatzikyriakou, Anna G Apostolidou, Eirini I Rigopoulou, Lazaros I Sakkas, Dimitrios Petrou Bogdanos
Konstantinos Gkiouras, Maria G Grammatikopoulou, Xenophon Theodoridis, Lazaros I Sakkas, Dimitrios Petrou Bogdanos, Department of Rheumatology and Clinical Immunology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Biopolis, Larissa GR41110, Greece
Konstantinos Gkiouras, Maria G Grammatikopoulou, Xenophon Theodoridis, Evangelia Chatzikyriakou, Faculty of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, University Campus, Thessaloniki GR54124, Greece
Maria G Grammatikopoulou, Anna G Apostolidou, Department of Nutritional Sciences and Dietetics, School of Health Sciences, International Hellenic University, Sindos Campus, Thessaloniki GR57400, Greece
Eirini Pagkalidou, Laboratory of Hygiene, Social and Preventive Medicine and Medical Statistics, Faculty of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, University Campus, Thessaloniki GR54124, Greece
Evangelia Chatzikyriakou, Laboratory of Clinical Neurophysiology, AHEPA University Hospital, Faculty of Medicine, Aristotle University of Thessaloniki, University Campus, Thessaloniki GR54124, Greece
Eirini I Rigopoulou, Department of Medicine and Research Laboratory of Internal Medicine, University Hospital of Larissa, Biopolis, Larissa GR41110, Greece
Dimitrios Petrou Bogdanos, Division of Transplantation, Immunology and Mucosal Biology, MRC Centre for Transplantation, King's College London Medical School, London GR41110, United Kingdom
Author contributions: Gkiouras K and Bogdanos DP designed research; Gkiouras K contributed to data acquisition, analyzed and interpreted data, drafting the article, final approval; Grammatikopoulou MG contributed to acquisition of data, interpreted data, drafting the manuscript, final approval; Theodoridis X contributed to quality assessment, interpreted data, revising the article, final approval; Pagkalidou E contributed to supervision of the statistical analyses, final approval; Chatzikyriakou E contributed to quality assessment of data, final approval; Apostolidou AG contributed to data acquisition, final approval; Rigopoulou EI and Sakkas LI contributed to data interpretation, drafting manuscript parts, final approval; Bogdanos DP contributed to conception and design of the study, acquisition of data, supervision of all analyses, critical revision, final approval.
Conflict-of-interest statement: The authors deny any conflict of interest.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Dimitrios Petrou Bogdanos, MD, PhD, Assistant Professor, Department of Rheumatology and Clinical Immunology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Biopolis, PO Box 1425, Larissa GR41110, Greece.
Received: November 1, 2019
Peer-review started: November 1, 2019
First decision: November 22, 2019
Revised: December 19, 2019
Accepted: January 2, 2020
Article in press: January 2, 2020
Published online: January 14, 2020

Non-invasive criteria are needed for Crohn’s disease (CD) diagnosis, with several biomarkers being tested. Results of individual diagnostic test accuracy studies assessing the diagnostic value of pancreatic autoantibodies-to-glycoprotein-2 (anti-GP2) tests for the diagnosis of CD appear promising.


To systematically review and meta-analyze evidence on the diagnostic accuracy of anti-GP2 tests in patients with suspected/confirmed CD.


An electronic search was conducted on PubMed, Cochrane-CENTRAL and grey literature (CRD42019125947). The structured research question in PICPTR format was “Population” including patients with symptoms akin to CD, the “Index test” being anti-GP2 testing, the “Comparator” involved standard CD diagnosis, the “Purpose of test” being diagnostic, “Target disorder” was CD, and the “Reference standard” included standard clinical, radiological, endoscopical, and histological CD diagnostic criteria. Quality was assessed with the Quality Assessment of Diagnostic Accuracy Studies-2 tool and hierarchical models were employed to synthesize the data.


Out of 722 studies retrieved, 15 were meta-analyzed. Thirteen studies had industry-related conflicts-of-interest, and most included healthy donors as controls (spectrum bias). For the combination of IgA and/or IgG anti-GP2 test, the summary sensitivity was 20% (95% confidence interval: 10%-29%) at a median specificity of 97%. If the test was applied in 10000 suspected patients, 9669 would be true negatives and in 26, the diagnosis would be missed. In this hypothetical cohort, the anti-GP2 would fail to produce a diagnosis for 81.3% of the positive cases. Low summary points of sensitivity and high specificity were estimated for the IgG or IgA anti-GP2 test. Analogous results were observed when the analyses were restricted using specific cut-offs, or when ulcerative colitis patients were used as comparators.


Anti-GP2 tests demonstrate low sensitivity and high specificity. These results indicate that caution is required before relying on its diagnostic value. Additionally, the need for improving the methodology of diagnostic test accuracy studies is evident.

Keywords: Inflammatory bowel disease, Gastrointestinal disease, Evidence-based diagnosis, Sensitivity, Specificity, Ulcerative colitis, Conflicts of interest, Meta-regression, Industry bias

Core tip: The majority of individual studies assessing the diagnostic accuracy of autoantibodies for anti-glycoprotein 2 (anti-GP2) for Crohn’s disease (CD) diagnosis either include asymptomatic participants, or patients with symptoms not akin to CD. Most studies carry industry-related conflicts-of-interest, employing non-blinded evaluation of their assays and CD diagnosis preceding anti-GP2 testing. The pooled analyses performed herein using only symptomatic patients as controls, revealed high heterogeneity and low diagnostic accuracy of the anti-GP2, demonstrating low sensitivity and high specificity. Based on the pooled sensitivity and specificity of the anti-GP2 for CD diagnosis, they do not appear to attain the characteristics to be used per se as a proper non-invasive diagnostic tool.