Study Identifies Antibodies Linked to PSC Disease Severity, Transplant-Free Survival

Anti-gliadin and anti-F-actin IgA antibodies may serve as valuable prognostic tools for identifying patients with primary sclerosing cholangitis (PSC) at risk of a more aggressive disease course and shortened transplant-free survival, according to findings from a recent study.1

Leveraging data from a prospective registry of patients with PSC seen at the Medical University of Warsaw and Pomeranian Medical University, the study calls attention to the prognostic potential of anti-gliadin IgA and anti-F-actin IgA for predicting disease severity and outcomes.1

“To the best of our knowledge, our study is the first report on a large prospective cohort of patients with PSC evaluating the clinical significance of IgA antibodies against F-actin and gliadin in this liver disease,” Piotr Milkiewicz, MD, a professor at Pomeranian Medical University, and colleagues wrote.1

A chronic and progressive cholestatic liver disorder of unknown etiology, PSC is characterized by inflammation, fibrosis, and stricturing of intrahepatic or extrahepatic biliary ducts. It frequently leads to complications of cholestasis and liver failure, but in the absence of a cure, management typically includes treatment with ursodeoxycholic acid and eventually a liver transplant. Given the varying and progressive nature of the disease, risk stratification with prognostic indicators could aid care for these patients.2

To assess the prevalence and clinical significance of anti-gliadin IgA and F-actin IgA antibodies in patients with PSC, investigators conducted a cohort study using prospective data from a local registry of consecutive patients with an established PSC diagnosis treated at 2 medical university centers in Poland.1

Investigators included all non-transplanted adult patients with PSC who had no other concomitant liver disease (n = 624). Additionally, 305 volunteers without any chronic liver disease, with similar gender and age as the study group, and residing in the same regions of Poland as the participants with PSC were also included.1

Investigators tested anti-gliadin and F-actin IgA antibodies in serum samples collected at the enrolment using QUANTA Lite ®enzyme-linked immunosorbent assays, applying the following cut-ff values for seropositivity: anti-F-actin IgA≥ 20 U and anti-gliadin IgA≥ 30 U. Seropositivity was assessed in the context of laboratory indicators of liver disease severity, presence of liver cirrhosis, and outcome measures including transplant-free survival and the occurrence of cholangiocarcinoma documented in the follow-up period.1

During a median follow-up of 18.5 (interquartile range [IQR], 8-33) months, 108 (17.2%) patients were transplanted, 29 (4.6%) died due to liver failure, and 33 (5.2%) were diagnosed with cholangiocarcinoma. Investigators called attention to greater median values for anti-gliadin IgA (11.4; IQR, 7.6-21.7 IU/L vs 7.4; IQR, 3.9-14.2 IU/L; P <.001) and anti-F-actin IgA (10.7; IQR, 7.3-15.4 IU/L vs 6.8; IQR, 5.0-8.8 IU/L; P <.001) in the study group than in the control group.1

Of note, the seropositivity rates for both antibodies were greater in patients with PSC than in healthy controls. For anti-gliadin IgA, the seropositivity rate was 14.6% for PSC patients compared with 4.6% for healthy subjects (odds ratio [OR], 3.55; 95% CI, 1.97-6.88; P <.001). For anti-F-actin IgA, the seropositivity rate was 12.0% for PSC patients compared with 2.95% for healthy subjects (OR, 4.50; 95% CI, 2.20-10.36; P <.001).1

Investigators observed significant associations between anti-F-actin and anti-gliadin IgA antibodies and the risk of liver-related death or transplantation (risk ratio [RR], 2.56; 95% CI, 1.9-3.5; P <.001 and RR, 1.95; 95% CI, 1.4-2.7; P <.001, respectively). Further analysis revealed positive anti-F-actin and anti-gliadin IgA antibodies were associated with shorter transplant-free survival (both P <.001).1

However, no association was found between the risk of cholangiocarcinoma for both anti-F-actin IgA (RR, 1.40; 95% CI, 0.56-3.55; P = .47) and anti-gliadin IgA (RR, 0.19; 95% CI, 0.03-1.41; P = .07).1

Investigators acknowledged multiple limitations to these findings, including the lack of diversity in the examined patient population; the inability to adjust for potential confounders not recorded in the registry; the limited power of association and risk stratification analyses due to the low occurrence of biliary malignancy during the study period; and the inability to infer causality due to the observational design of the study.1

“We have shown that both antibodies identified patient populations with a distinct, more severe clinical picture, and were independent predictors of poor survival,” investigators concluded.1 “We believe that our work will contribute to improved management of patients with PSC and aid the development of novel predictive models of outcome.”

References

1. Wunsch E, Milkiewicz M, Norman GL, et al. Prognostic significance of anti-gliadin and anti-F-actin IgA antibodies in primary sclerosing cholangitis. Pol Arch Intern Med. doi:10.20452/pamw.16910.
2. Rawla P, Samant H. Primary Sclerosing Cholangitis. StatPearls. February 12, 2023. Accessed January 6, 2025. https://www.ncbi.nlm.nih.gov/books/NBK537181/