PIgR Autoantibody-abundant Circulating Vesicles Contributes to Biliary Injury in Biliary Atresia.

PURPOSE: This study aimed to elucidate the role of polymeric immunoglobulin receptor (pIgR) autoantibodies in the pathogenic progression of biliary atresia (BA).

METHODS

The presence and levels of plasma pIgR autoantibodies, pIgR antigen expression, and B cell counts were assessed in liver tissues. Serum extracellular vesicles (EVs) were isolated, quantified, and characterized. The functional roles of EVs enriched with pIgR autoantibodies in biliary injury were investigated.

RESULTS

Infants diagnosed with BA exhibited significantly elevated levels of plasma pIgR autoantibodies, which positively correlated with hepatic inflammation. The expression levels of pIgR autoantibodies demonstrated high accuracy in distinguishing BA from non-BA controls. Notably, the presence of pIgR antigens was specifically observed in cholangiocytes and was associated with an increased number of CD27+ memory B cells within the liver tissue. Furthermore, the concentration of pIgR autoantibodies was found to be higher in EVs derived from BA patients compared to those from control subjects. EVs enriched with pIgR autoantibodies induced biliary injury potentially through activation of the extracellular signal-regulated kinase (ERK) pathway.

CONCLUSIONS

Our findings suggest that pIgR autoantibody may serve as a potential biomarker for differentiating infants with BA from those without it. Additionally, these results indicate that EVs enriched with pIgR autoantibody could play a significant role in the underlying pathogenesis of BA.