• Ewa Wunsch, Małgorzata Milkiewicz, Gary L Norman, Alicja Łaba, Beata Kruk, and Piotr Milkiewicz.
• Pol. Arch. Med. Wewn. 2025 Jan 2.

IntroductionPrimary sclerosing cholangitis (PSC) is a biliary disorder associated with a high risk of end-stage liver disease and cholangiocarcinoma (CCA). Currently prediction of the unfavorable outcomes is hindered by the lack of valuable prognostic biomarkers.ObjectivesThe aim of the study was to assess the prevalence of the autoantibodies in PSC and define their potential use as the predictors of progressive disease and CCA in a large, prospective cohort of PSC patients.Patients And MethodsEnzyme-linked immunosorbent assay was applied for detection of anti-gliadin ≥30 U and anti-F-actin ≥20 U IgA antibodies in sera of 624 patients with PSC and 305 healthy controls. Poor PSC outcomes were defined as: (i.) liver transplantation or/and liver disease-related death, i.e. transplantation-free survival and (ii.) CCA.ResultsAnti-gliadin and anti-F-actin IgA antibodies were more frequent in PSC than in healthy controls (P<0.001 for both). The autoantibodies were associated with laboratory indices liver disease severity, including MELD score and anti-F-actin - with cirrhosis (P<0.001). During a median (IQR) follow-up of 18.5 (8-33) months, 17.2% patients were transplanted, 4.6% died due to their liver disease, and 5.2% were diagnosed with CCA. Associations between anti-F-actin and anti-gliadin and a shorter transplantation-free survival (P<0.001 for both) were found. In the multivariable Cox proportional hazard regression analysis anti-gliadin was an independent predictor of poor survival. No association between analyzed antibodies and the incidence of CCA was detected.ConclusionsAnti-gliadin and anti-F-actin IgA identify the subgroup of PSC patients with the more severe disease and at risk of shortened transplantation-free survival.

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