Maternal microchimerism in biliary atresia.

本研究的目的是为了确定胆道闭锁(BA)患者肝脏中母体微嵌合体的存在和程度。根据受试者的性别进行了两系列调查。其中6人拥有学士学位。用X和Y染色体探针和荧光原位杂交(FISH)对肝脏进行分析。第二组受试者为女性。9例BA患者及其母亲均为HLA型(I类)。同时还检测了母体和其他人类白细胞抗原(HLA)的抗体。2例新生儿肝炎、2例Alagille综合征和1例Byler综合征作为对照。所有男性BA肝脏都含有带有1条和2条X染色体(即XY或XX)的混合细胞。男性对照组的所有肝脏都只有一条X染色体(即XY)。所有女性BA受试者的胆管上皮和肝细胞均有不同程度的抗母体HLAI类抗体(5例强，3例弱，1例弱)。来自女性对照的肝脏没有显示任何抗母体的人类白细胞抗原-I类抗体(HLA-Ab)。我们的初步数据似乎表明，进行性出生后型BA患者的肝脏中存在母体微嵌合体。我们认为BA实际上可能是一种移植物抗宿主病，伪装成由母体微嵌合体引发的自身免疫反应，我们将进一步探讨这一假说，以阐明BA的病因。

The aim of this study was to determine the existence and extent of maternal microchimerism in the livers of biliary atresia (BA) patients.Two series of investigations were performed based on the sex of our subjects.Subjects for series I were male. Six had BA. Livers were analyzed using X and Y chromosome probes and fluorescent in situ hybridization (FISH).Subjects for series II were female. Nine BA cases and their mothers were HLA typed (class I). Daughter livers were also tested for antibodies to maternal and other HLA.Two cases of neonatal hepatitis, 2 cases of Alagille syndrome, and 1 case of Byler's syndrome acted as controls.All male BA livers were found to contain a mixture of cells with one and two X chromosomes (i.e., XY or XX). All livers from male controls had only one X chromosome (i.e., XY). All female BA subjects had varying intensities of anti-maternal HLA-class I (HLA-A) antibodies in their bile duct epithelium and hepatocytes (strong in 5, mild in 3 and weak in 1). The liver from the female control did not display any anti-maternal HLA-class I antibodies (HLA-Ab).Our preliminary data appear to show that maternal microchimerism is present within the livers of patients with progressive postnatal type BA. We suggest that BA could in fact be a graft versus host disease masquerading as an autoimmune reaction triggered by maternal microchimerism and we will pursue this hypothesis further to clarify the etiology of BA.