Kobayashi Hiroyuki, Tamatani Takuya, Tamura Tsuyoshi, Kusafuka Junichi, Yamataka Atsuyuki, Lane Geoffrey J, Kawasaki Seiji, Ishizaki Yoichi, Mizuta Koichi, Kawarasaki Hideo, Gittes George K
Department of Pediatric General and Urogenital Surgery, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
J Pediatr Surg. 2007 Jun;42(6):987-91; discussion 991. doi: 10.1016/j.jpedsurg.2007.01.051.
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 men, of which 6 had BA. Livers were analyzed using X and Y chromosome probes and fluorescent in situ hybridization. Subjects for series II were woman. 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 syndrome acted as controls.
All male BA livers were found to contain a mixture of cells with 1 and 2 X chromosomes (ie, XY or XX). All livers from male controls had only 1 X chromosome (ie, XY). All female BA subjects had varying intensities of antimaternal HLA class I (HLA-A) antibodies in their bile duct epithelium and hepatocytes (strong, 5; mild, 3; weak, 1). The liver from the female control did not display any antimaternal 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-vs-host disease masquerading as an autoimmune reaction triggered by maternal microchimerism, and we intend to pursue this hypothesis further to clarify the etiology of BA.
本研究的目的是确定胆道闭锁（BA）患者肝脏中母体微嵌合体的存在情况及程度。
根据研究对象的性别进行了两组调查。第一组的研究对象为男性，其中6例患有BA。使用X和Y染色体探针及荧光原位杂交技术对肝脏进行分析。第二组的研究对象为女性。对9例BA病例及其母亲进行了HLA分型（I类）。还检测了女儿肝脏中针对母体及其他HLA的抗体。2例新生儿肝炎、2例阿拉吉列综合征和1例贝勒综合征患者作为对照。
所有男性BA患者的肝脏均发现含有具有1条和2条X染色体的细胞混合物（即XY或XX）。所有男性对照的肝脏均只有1条X染色体（即XY）。所有女性BA患者的胆管上皮和肝细胞中均有不同强度的抗母体HLA I类（HLA-A）抗体（强阳性5例；弱阳性3例；弱阳性1例）。女性对照的肝脏未显示任何抗母体HLA I类抗体（HLA-Ab）。
我们的初步数据似乎表明，进行性产后型BA患者的肝脏中存在母体微嵌合体。我们认为BA实际上可能是一种伪装成由母体微嵌合体引发的自身免疫反应的移植物抗宿主病，我们打算进一步探究这一假说以阐明BA的病因。
