Introduction
Primary sclerosing cholangitis (PSC) is a chronic, progressive cholestatic disorder of the bile ducts, associated with significant morbidity and an increased risk of malignancy. Preclinical studies in mice deficient in the multidrug resistance protein 2 (Mdr2−/−) have demonstrated that the integrin αvβ6 plays a critical role in biliary fibrosis by activating latent transforming growth factor (TGF)-β1, the main profibrotic cytokine in the liver. Moreover, several studies have shown that autoantibodies against integrin αvβ6 exhibit good diagnostic accuracy in ulcerative colitis (UC). The aim of this meta-analysis is to evaluate the diagnostic performance of anti-integrin αvβ6 autoantibodies in PSC.
Aims & Methods
A systematic review and meta-analysis were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Four electronic databases (PubMed, Scopus, ScienceDirect, and the Cochrane Library) were systematically searched up to February 2025. Eligible studies included those involving patients with PSC as well as non-PSC control groups, in which the overall sensitivity and specificity of serum anti-integrin αvβ6 autoantibodies for the diagnosis of PSC were reported. Pooled sensitivity, specificity, and area under the curve (AUC) were calculated using a random-effects model. Subgroup analyses were conducted based on the presence or absence of concomitant UC. Meta-analyses were performed using RevMan version 5.4.
Results
Four studies, comprising a total of 1,228 participants, met the predefined eligibility criteria. All studies defined the positivity threshold as the mean value in control groups plus three standard deviations (SD). The pooled sensitivity and specificity for the diagnosis of PSC were 0.679 (95% CI: 0.670–0.689) and 0.940 (95% CI: 0.939–0.941), respectively, with high heterogeneity (I² = 99%).
In the subgroup analysis, the sensitivity and specificity of the test for diagnosing PSC in the absence of concomitant UC were 0.075 (95% CI: 0.071–0.080) and 0.940 (95% CI: 0.939–0.941), respectively. In contrast, in the subgroup of patients with both PSC and UC, sensitivity reached 0.960 (95% CI: 0.959–0.961), while specificity was 0.720 (95% CI: 0.713–0.727).
Sensitivity analyses performed to explore the observed heterogeneity revealed that exclusion of one study (Bloeman, 2024) significantly improved diagnostic performance across all subgroups, with a pooled sensitivity of 0.831 (95% CI: 0.8236–0.8384) and specificity of 0.946 (95% CI: 0.9451–0.9468).
Conclusion
Serum anti-integrin αvβ6 autoantibodies demonstrate diagnostic value in PSC, with consistently high specificity across all patient groups and notably high sensitivity in those with concomitant ulcerative colitis. The high specificity supports a strong negative predictive value. Given the supporting preclinical evidence, integrin αvβ6 warrants further investigation not only as a diagnostic biomarker but also as a potential therapeutic target.
Disclosure
No conflict of Interest