Maternal microchimerism in underlying pathogenesis of biliary atresia: quantification and phenotypes of maternal cells in the liver.
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.
Muraji
Toshihiro
T
Department of Surgery, Kobe Children's Hospital, Kobe, Japan. t-muraji@ibaraki-kodomo.com
Hosaka
Naoki
N
Irie
Naoki
N
Yoshida
Makiko
M
Imai
Yukihiro
Y
Tanaka
Kohichi
K
Takada
Yasutsugu
Y
Sakamoto
Seisuke
S
Haga
Hironori
H
Ikehara
Susumu
S
D001656:Biliary Atresia / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D001707:Biopsy, Needle; D018414:CD8-Positive T-Lymphocytes; D016022:Case-Control Studies; D046528:Chimerism / Q000196:embryology*; D041321:Chromosomes, Human, X; D041322:Chromosomes, Human, Y; D018507:Gene Expression Regulation, Developmental; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008107:Liver Diseases / Q000235:genetics* / Q000473:pathology; D008297:Male; D011336:Probability; D012016:Reference Values; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D046509:Tissue Culture Techniques