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Maternal microchimerism in the livers of patients with biliary atresia
David L Suskind1, Philip Rosenthal, Melvin B Heyman
1Department of Pediatrics, University of California, San Francisco, USA. david.suskind@seattlechildrens.org
Background:
Biliary atresia (BA) is a neonatal cholestatic disease of unknown etiology. It is the leading cause of liver transplantation in children. Many similarities exist between BA and graft versus host disease suggesting engraftment of maternal cells during gestation could result in immune responses that lead to BA. The aim of this study was to determine the presence and extent of maternal microchimerism (MM) in the livers of infants with BA.
Methods:
Using fluorescent in situ hybridization (FISH), 11 male BA & 4 male neonatal hepatitis (NH) livers, which served as controls, were analyzed for X and Y-chromosomes. To further investigate MM in BA, 3 patients with BA, and their mothers, were HLA typed. Using immunohistochemical stains, the BA livers were examined for MM. Four additional BA livers underwent analysis by polymerase chain reaction (PCR) for evidence of MM.
Results:
By FISH, 8 BA and 2 NH livers were interpretable. Seven of eight BA specimens showed evidence of MM. The number of maternal cells ranged from 2-4 maternal cells per biopsy slide. Neither NH specimen showed evidence of MM. In addition, immunohistochemical stains confirmed evidence of MM. Using PCR, a range of 1-142 copies of maternal DNA per 25,000 copies of patients DNA was found.
Conclusions:
Maternal microchimerism is present in the livers of patients with BA and may contribute to the pathogenesis of BA.
