• Ewa Wunsch, Małgorzata Milkiewicz, Gary L Norman, Alicja Łaba, Beata Kruk, and Piotr Milkiewicz.
• Department of Translational Medicine, Pomeranian Medical University in Szczecin, Szczecin, Poland. ewa.wunsch@pum.edu.pl
• Pol. Arch. Med. Wewn. 2025 Jan 30; 135 (1).

IntroductionPrimary sclerosing cholangitis (PSC) is a biliary disorder associated with a high risk of end‑stage liver disease and cholangiocarcinoma (CCA). Currently, prediction of unfavorable outcomes is hindered by a lack of valuable prognostic biomarkers.ObjectivesThe aim of the study was to assess the prevalence of autoantibodies in PSC and define their potential use as the predictors of the disease progress and CCA in a large, prospective cohort of PSC patients.Patients And MethodsEnzyme‑linked immunosorbent assay was applied for detection of serum immunoglobulin (Ig) A anti‑gliadin antibodies at a concentration equal to or above 30 U and anti‑F‑actin antibodies at a concentration equal to or above 20 U in 624 patients with PSC and 305 healthy controls. Poor PSC outcomes were defined as liver transplantation or / and liver disease‑related death, that is, transplantation‑free survival, and CCA.ResultsAnti‑gliadin and anti‑F‑actin IgA antibodies were more frequent in the PSC patients than in the healthy controls (P <0.001 for both). The autoantibodies were associated with laboratory indices of the liver disease severity, including the model of end‑stage liver disease score, and anti‑F‑actin was associated with cirrhosis (P <0.001). During a median (interquartile range) 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 hazards regression analysis anti‑gliadin was an independent predictor of poor survival. No association between the analyzed antibodies and the incidence of CCA was detected.ConclusionsAnti‑gliadin and anti‑F‑actin IgA identify the subgroup of PSC patients with a more severe disease and at a risk of shortened transplantation‑free survival.

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