Anti‐Integrin αvβ6 Autoantibodies as Diagnostic and Monitoring Biomarkers for Pediatric‐Onset Primary Sclerosing Cholangitis

AIM: Pediatric primary sclerosing cholangitis (PSC) is a rare progressive cholestatic liver disease that often presents diagnostic challenges owing to overlapping clinical and histological features with autoimmune hepatitis (AIH). We hypothesized that anti-integrin αvβ6 autoantibodies may serve as a noninvasive biomarker to differentiate pediatric PSC from AIH and monitor disease activity. METHODS: We retrospectively analyzed serum samples from 65 patients with pediatric-onset PSC, 39 with AIH, and 66 controls. Anti-integrin αvβ6 autoantibodies were quantified using enzyme-linked immunosorbent assay. Functional activity of the autoantibodies was assessed using a solid-phase fibronectin-binding inhibition assay. RESULTS: Anti-integrin αvβ6 autoantibody levels were significantly higher in pediatric-onset PSC than in AIH and controls. The sensitivity and specificity for distinguishing PSC were 63.9% (95% confidence interval [CI]: 51.4-74.8) and 97.1% (95% CI: 91.9-99.2), respectively. Higher levels were observed in PSC with inflammatory bowel disease than without (p = 0.0069) and in PSC-AIH overlap compared with AIH alone (p = 0.0018). In one case, rising autoantibody levels preceded the clinical transition from AIH to PSC-AIH overlap. Levels declined during remission and after liver transplantation; however, increased again upon recurrence. Functional assays demonstrated that autoantibodies from patients with pediatric-onset PSC inhibited binding of integrin αvβ6 to fibronectin. CONCLUSIONS: Anti-integrin αvβ6 autoantibodies may serve as a noninvasive clinically informative biomarker for distinguishing pediatric-onset PSC from AIH and reflecting longitudinal changes in disease activity, including posttransplant recurrence. These findings support their potential clinical utility in the diagnosis and longitudinal assessment of pediatric-onset PSC.