Diagnostic and clinical significance of antigen-specific pancreatic antibodies in inflammatory bowel diseases: A meta-analysis

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