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Updated: Jul 7, 2026
A Mouse Model of Chronic Liver Fibrosis for the Study of Biliary Atresia
Published on: February 3, 2023
Maternal microchimerism in underlying pathogenesis of biliary atresia: quantification and phenotypes of maternal
Toshihiro Muraji1, Naoki Hosaka, Naoki Irie
1Department of Surgery, Kobe Children's Hospital, Kobe, Japan. t-muraji@ibaraki-kodomo.com
Objective:
The goal was to examine whether microchimerism plays a crucial role in the pathogenesis of biliary atresia; we analyzed the localization of maternal microchimeric cells and their phenotypes.
Methods:
Liver biopsy specimens from 8 male infants with biliary atresia and 6 control subjects with other liver diseases were investigated for maternal chimeric cells and their phenotypes through double-staining fluorescence in situ hybridization and immunohistochemical analyses.
Results:
Significantly larger numbers of maternal XX+ cells were found in the portal area and sinusoids of patients with biliary atresia, in comparison with control patients. In phenotypic analyses of XX+ cells, CD8+ T cells, CD45+ cells, and cytokeratin-positive cells were found, and the numbers and proportions among total CD8+ T cells were significantly higher than those in control patients.
Conclusions:
Significantly more maternal chimeric CD8+ T cells in the livers of patients with biliary atresia suggest that maternal immunologic insults represent the underlying pathogenesis in biliary atresia. The findings support the recently postulated mechanisms of alloautoimmune and/or autoalloimmune responses.
Insights
Maternal microchimeric cells, particularly CD8+ T cells, are significantly increased in the livers of infants with biliary atresia, suggesting maternal immune responses contribute to this condition.
Area of Science:
- Hepatology
- Immunology
- Pediatric Gastroenterology
Background:
- Biliary atresia is a severe neonatal liver disease.
- The role of microchimerism in biliary atresia pathogenesis is not fully understood.
Purpose of the Study:
- To investigate the presence and phenotype of maternal microchimeric cells in biliary atresia.
- To determine if microchimerism is involved in the development of biliary atresia.
Main Methods:
- Analysis of liver biopsy specimens from infants with biliary atresia and controls.
- Utilized double-staining fluorescence in situ hybridization and immunohistochemistry.
- Examined maternal XX+ cells and their phenotypes (CD8+ T cells, CD45+, cytokeratin+).
Main Results:
- Significantly higher numbers of maternal XX+ cells were found in the portal area and sinusoids of biliary atresia patients.
- Maternal CD8+ T cells, CD45+ cells, and cytokeratin-positive cells were identified in XX+ cells.
- Increased proportions of maternal CD8+ T cells were observed in biliary atresia livers.
Conclusions:
- Elevated maternal chimeric CD8+ T cells suggest maternal immunologic insults in biliary atresia pathogenesis.
- Findings support alloautoimmune and/or autoalloimmune response mechanisms.
- Microchimerism may play a critical role in the development of biliary atresia.
