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Pathogenesis and antigen localization in immune reaction against tissue-specific antigens in liver transplantation

肝移植中组织特异性抗原免疫反应的发病机制和抗原定位

基本信息

批准号：
17390347
负责人：
KIUCHI Tetsuya
金额：
$ 10.05万
依托单位：
Nagoya University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

项目摘要

Liver dysfunction accompanied by de novo serum auto-antibody was observed in 9 (19%) of 48 pediatric liver transplant patients followed for 27 months in median. There was no gender deviation and onset was 2-71 (median 27) months after transplantation. The patients received liver transplant at the age of 0.5-25.3 (median 13) years. Six patients developed anti-nuclear antibody (ANA), two anti-smooth muscle antibody, and two anti-LKM-1 antibody, two of whom was accompanied by increase of IgG. Graft histology was more or less compatible with acute rejection combined with interface hepatitis. All cases responded to corticosteroid and azathiopurine. This group combined with other children with similar symptoms were studied as posttransplant de novo autoimmune hepatitis (AIH).To specify antigen-antibody reaction in de novo AIH, tissue crossmatch between sera at the onset or after treatment and graft liver tissue was done. Although some antigen-antibody reaction was observed on bile duct and portal and hepatic venous endothelium, similar reactions were occasionally observed in cases without de novo AIH. The extent or loci of the reaction varied. It is conjectured that de novo antibody production against graft liver led to the pathogenesis of the disease. A strong reaction on the biliary epithelium was observed in another case with ductopenic chronic rejection, in which identification, timing, and trigger of antibody production are under investigation.Because some report regards de novoAIH as a type of chronic reject ion, the comparison with ductopenic rejection is full of implications. Although identification of antibodies specific to de novo AIH is under process, comparison between ductopenic chronic rejection and de novo AIH is expected to lead to the elucidation of the role of de novo antibody in pediatric liver transplantation and to the possibility that the difference of target antigen can discriminate the two distinct pathogenesis.

在48例中位随访27个月的儿童肝移植患者中，9例（19%）观察到肝功能障碍伴新发血清自身抗体。无性别差异，发病时间为移植后2-71（中位数27）个月。患者接受肝移植的年龄为0.5-25.3（中位数13）岁。6例患者出现抗核抗体（ANA），2例出现抗平滑肌抗体，2例出现抗LKM-1抗体，其中2例伴有IgG升高。移植物组织学或多或少与急性排斥反应合并界面性肝炎相一致。所有病例均对皮质类固醇和硫唑嘌呤有反应。将本组患儿与其他有类似症状的患儿作为移植后新发自身免疫性肝炎（AIH）进行研究，并将发病时或治疗后的血清与移植肝组织进行交叉配型，以明确新发AIH的抗原抗体反应。虽然在胆管、门静脉和肝静脉内皮上观察到一些抗原抗体反应，但在非新发AIH病例中偶尔观察到类似反应。反应的程度或部位各不相同。作者认为，抗移植肝抗体的重新产生是本病的发病机制之一。在另一例胆管减少性慢性排斥反应中观察到胆管上皮的强烈反应，其中抗体产生的识别、时间和触发因素正在研究中，因为有些报告将新发AIH视为一种慢性排斥反应，因此与胆管减少性排斥反应的比较充满了意义。虽然新生AIH特异性抗体的鉴定正在进行中，但导管减少性慢性排斥反应和新生AIH之间的比较有望阐明新生抗体在小儿肝移植中的作用，并可能导致靶抗原的差异可以区分两种不同的发病机制。