Maternal microchimerism in biliary atresia.

胆道闭锁的母体微嵌合现象。

• 批准号: 16591789
• 负责人: KOBAYASHI Hiroyuki
• 金额: $ 1.22万
• 依托单位: Juntendo University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591789/
• 关键词: Biliary Atresia; maternal microchimerism; chromosome; fluorescent in situ hybridization; graft versus host disease; マイクロキメリズム; HLA; 病因; 肝線維化; Fibrocyte; X-Xchromosomes

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.

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和程度，根据我们研究对象的性别进行了两个系列的研究。六个是BA。用X和Y染色体探针和荧光原位杂交（FISH）分析肝脏。系列II的受试者为女性。9例BA患者及其母亲均为HLA I型。还检测了子代肝脏的母亲和其他HLA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。发现所有男性BA肝脏都含有一个和两个X染色体的细胞混合物（即，XY或XX）。来自雄性对照的所有肝脏只有一条X染色体（即，XY）。所有女性BA受试者的胆管上皮和肝细胞中均存在不同强度的抗母体HLA-I类（HLA-A）抗体（5例强，3例轻度，1例弱）。来自雌性对照的肝脏没有显示任何抗母体HLA-I类抗体（HLA-Ab）。我们的初步数据似乎表明，母体微嵌合体存在于进行性出生后BA型患者的肝脏中。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，我们将进一步探讨这一假说以阐明BA的病因。

项目成果

Two-way cell traffic between mother and fetus : biologic and clinical implications.

母亲和胎儿之间的双向细胞交通：生物学和临床意义。

• 发表时间: 2007
• 期刊: Blood 88
• 作者: Lo YM;Lo ES;Watson N;et al.
• 通讯作者: et al.

The role of monocyte chemoattractant protein-1 in biliary atresia

• DOI: 10.1016/j.jpedsurg.2006.08.018
• 发表时间: 2006-12-01
• 期刊: JOURNAL OF PEDIATRIC SURGERY
• 影响因子: 2.4
• 作者: Kobayashi, Hiroyuki;Tamatani, Takuya;Miyano, Takeshi
• 通讯作者: Miyano, Takeshi

Serum concentration of adhesion molecules in postoperative biliary atresia patients: Relationship to disease activity and cirrhosis

• DOI: 10.1053/jpsu.2001.25798
• 发表时间: 2001-08-01
• 期刊: JOURNAL OF PEDIATRIC SURGERY
• 影响因子: 2.4
• 作者: Kobayashi, H;Horikoshi, K;Miyano, T
• 通讯作者: Miyano, T

Maternal microchimerism in biliary atresia

• DOI: 10.1016/j.jpedsurg.2007.01.051
• 发表时间: 2007-06-01
• 期刊: JOURNAL OF PEDIATRIC SURGERY
• 影响因子: 2.4
• 作者: Kobayashi, Hiroyuki;Tamatani, Takuya;Gittes, George K.
• 通讯作者: Gittes, George K.

Innovative modification of the hepatic portoenterostomy. Our experience of treating biliary atresia.

肝门肠造口术的创新修改。

• 发表时间: 2006
• 期刊: J Pediatr Surg 41
• 作者: Kobayashi H*;Yamataka A;Urao M;Okazaki T;Yanai T;Koga H;Lane GJ;Miyano T
• 通讯作者: Miyano T