Published online Jan 14, 2020. doi: 10.3748/wjg.v26.i2.246
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.
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.