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

Weipeng Wang; Ying Zhou; Ying Lu; Bo Wu; Shicheng Peng; Wei Cai; Yongtao Xiao

doi:10.1016/j.jpedsurg.2024.162116

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

J Pediatr Surg. 2024 Dec 20;60(3):162116. doi: 10.1016/j.jpedsurg.2024.162116. Online ahead of print.

Authors

Weipeng Wang¹, Ying Zhou¹, Ying Lu², Bo Wu³, Shicheng Peng², Wei Cai⁴, Yongtao Xiao⁵

Affiliations

¹ Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China.
² Shanghai Institute for Pediatric Research, Shanghai 200092, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai 200092, China.
³ Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China; Division of Pediatric Gastroenterology and Nutrition, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai 200092, China.
⁴ Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China; Division of Pediatric Gastroenterology and Nutrition, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China; Shanghai Institute for Pediatric Research, Shanghai 200092, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai 200092, China. Electronic address: [email protected].
⁵ Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China; Division of Pediatric Gastroenterology and Nutrition, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China; Shanghai Institute for Pediatric Research, Shanghai 200092, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai 200092, China. Electronic address: [email protected].

PMID: 39733605
DOI: 10.1016/j.jpedsurg.2024.162116

Abstract

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.

Keywords: Autoantibody; Biliary atresia; Extracellular vesicles; pIgR.