Biliary atresia: graft-versus-host disease with maternal microchimerism as an etiopathogenesis

Ryuta Masuya; Toshihiro Muraji; Toshio Harumatsu; Mitsuru Muto; Kazuhiko Nakame; Atsushi Nanashima; Satoshi Ieiri

doi:10.1016/j.transci.2022.103410

Biliary atresia: graft-versus-host disease with maternal microchimerism as an etiopathogenesis

Transfus Apher Sci. 2022 Apr;61(2):103410. doi: 10.1016/j.transci.2022.103410. Epub 2022 Mar 11.

Authors

Ryuta Masuya¹, Toshihiro Muraji², Toshio Harumatsu³, Mitsuru Muto³, Kazuhiko Nakame¹, Atsushi Nanashima⁴, Satoshi Ieiri⁵

Affiliations

¹ Division of the Gastrointestinal, Endocrine and Pediatric Surgery, Department of Surgery, Faculty of Medicine, University of Miyazaki, Japan.
² Department of Pediatric Surgery, Research Field in Medical and Health Sciences, Medical and Dental Area, Research and Education Assembly, Kagoshima University, Japan; Department of Pediatric Surgery, Kirishima Medical Center, Japan.
³ Department of Pediatric Surgery, Research Field in Medical and Health Sciences, Medical and Dental Area, Research and Education Assembly, Kagoshima University, Japan.
⁴ Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Faculty of Medicine, University of Miyazaki, Japan.
⁵ Department of Pediatric Surgery, Research Field in Medical and Health Sciences, Medical and Dental Area, Research and Education Assembly, Kagoshima University, Japan. Electronic address: sieiri@m.kufm.kagoshima-u.ac.jp.

PMID: 35288054
DOI: 10.1016/j.transci.2022.103410

Abstract

Biliary atresia (BA) is an inflammatory disease of the biliary system in newborns and infants. The etiology is largely unknown. Approximately half of BA patients require liver transplantation by 20 years of age, even after surgical correction due to progressive fibrosis of the liver. Regarding the disease mechanism, there is circumstantial evidence to support the hypothesis of graft-versus-host disease because of the existence of maternal cells in the liver (maternal microchimerism, MMC), histopathological similarity of the liver and an intense maternal response to the BA patient with mixed lymphocyte culture. Immune dysregulation with decreased Treg and increased Th1 and Th17 cells are the pathogenic features of BA, which are homologous to the pathogenic features of GvHD. Further elucidation of the etiopathogenetic mechanism of BA is warranted for development of new therapeutic strategies for native liver survival.

Keywords: Biliary atresia; Graft-versus-host disease; Maternal microchimerism; Th17; Treg.

MeSH terms

Biliary Atresia* / pathology
Biliary Atresia* / surgery
Chimerism
Graft vs Host Disease* / etiology
Graft vs Host Disease* / pathology
Humans
Infant
Infant, Newborn
Liver / pathology
Liver Transplantation* / adverse effects