PMID: 39844835 https://pubmed.ncbi.nlm.nih.gov/39844835/

Abstract

BACKGROUND: Primary biliary cholangitis (PBC) is a cholestatic, autoimmune liver disease with the presence of characteristic autoantibodies. The aim of the work was to determine the level of antibodies directed against bacterial antigens: (anti-anti), (anti-), (anti- ) and () in sera of PBC patients. We also performed studies on the impact of the bacterial peptides on the specific antigen-antibody binding.

METHOD: We screened 92 Polish PBC patients and sera samples from healthy donors and pathological controls. Autoantibodies and anti-bacterial antibodies were determined by commercially available ELISA kits. Specific inhibition of antibody binding was also detected by the in house ELISA method.

RESULTS: Anti-, anti-, anti-, anti- and anti- antibodies were significantly more common in the group of PBC patients than in the pathological and healthy control groups: 74%, 40%, 84%, 39% and 69% respectively. The mean level of anti-, anti- , anti- anti- in the PBC group was significantly higher than those in the healthy group ( < 0.001). and in patients with other liver diseases. In sera of patients with the presence of positive anti-mitochondrial antibodies (AMA), specific for PBC, anti-bacterial antibodies have been found in 80% vs. 50% in sera with AMA negative. We observed inhibition of specific antigen-antibody binding by the bacterial peptide: EClpP ( caseinolytic protease) and adenine glycosylase from caseinolytic protease P, ClpP from peptide of , PDC from peptide and adenine glycosylase of . Bacterial factors influence the specific binding of antibodies to pyruvate dehydrogenase (PDC-E2), gp210 and KLHL12 (kelch-like peptide 12) antigens.

CONCLUSION: Microbial mimics may be the major targets of cross-reactivity with human pyruvate dehydrogenase, gp210, and KLHL12 in PBC.