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
Processing time: 72 Days and 17.9 Hours
Research background

Non-invasive criteria are needed for Crohn’s disease (CD) diagnosis, with several biomarkers being tested, including the pancreatic autoantibodies-to-glycoprotein-2 (anti-GP2).

Research motivation

Results of individual diagnostic test accuracy (DTA) studies assessing the diagnostic value of the anti-GP2 for the diagnosis of CD appear promising, however, a systematic review and meta-analysis of the studies is still lacking.

Research objectives

The aim of the present systematic review and meta-analysis was synthesize all evidence on the diagnostic accuracy of anti-GP2 tests in patients with suspected/confirmed CD.

Research methods

An electronic search was conducted on Medline, Cochrane-CENTRAL and grey literature. Quality was assessed with the Quality Assessment of Diagnostic Accuracy Studies-2 tool and hierarchical models were employed to synthesize the data. The hierarchical summary receiver operating characteristic (HSROC) model was employed to synthesize data. SROC curves were constructed and since a summary point of sensitivity or specificity with studies using mixed thresholds would be clinically uninterpretable, the summary sensitivity was estimated at its median specificity, based on the SROC curves. Heterogeneity was assessed statistically by including covariates in the HSROC model (meta-regression) and was summarized with the Relative Diagnostic Odds Ratios.

Research results

Out of 722 studies retrieved, 15 were meta-analyzed. Thirteen studies had industry-related conflicts-of-interest, and most included healthy donors as controls. For the combination of IgA and/or IgG anti-GP2 test, the summary sensitivity was 20% at a median specificity of 97%.

Research conclusions

The anti-GP2 demonstrated low sensitivity and high specificity. These results indicate caution before relying on its diagnostic value. However, the anti-GP2 appear to attain all characteristics of a screening tool rather than a diagnostic one. Therefore, based on the available evidence, the use of the anti-GP2 for CD diagnosis is not warranted. Furthermore, overall quality of DTA studies appears low, with many carrying industry-related, spectrum, test-review and partial verification bias. Thus, the need for improving the methodology of DTA studies is evident.

Research perspectives

The majority of DTA studies are lacking a quality design and should be synthetized with caution. Future research should assess differences between industry-funded and non-industry funded DTA studies.