Published online February 29, 2008
PEDIATRICS Vol. 121 No. 3 March 2008, pp. 517-521 (doi:10.1542/peds.2007-0568)

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ARTICLE

Maternal Microchimerism in Underlying Pathogenesis of Biliary Atresia: Quantification and Phenotypes of Maternal Cells in the Liver

Toshihiro Muraji, MD^a, Naoki Hosaka, MD^b, Naoki Irie, PhD^c, Makiko Yoshida, MD^d, Yukihiro Imai, MD^e, Kohichi Tanaka, MD^f, Yasutsugu Takada, MD^g, Seisuke Sakamoto, MD^g, Hironori Haga, MD^h and Susumu Ikehara, MD^b

Departments of ^a Surgery
^d Pathology, Kobe Children's Hospital, Kobe, Japan
^b First Department of Pathology, Kansai Medical University, Osaka, Japan
^c Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan
Departments of ^g Surgery
^h Clinical Pathology, Kyoto University Gradate School of Medicine, Kyoto, Japan
^e Department of Pathology, Kobe City General Hospital, Kobe, Japan
^f Institute for Biomedical Research and Innovation, Kobe, Japan

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.

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Key Words: biliary atresia • graft-versus-host disease • microchimerism • CD8

Abbreviations: BA—biliary atresia • GvHD—graft-versus-host disease • BEC—biliary epithelial cell • FISH—fluorescence in situ hybridization

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Accepted Aug 1, 2007.

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