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

48例儿童肝移植患者中位随访27个月，9例(19%)出现肝功能障碍，并伴有新发血清自身抗体。无性别差异，发病时间为移植后2~71个月(中位数27个月)。患者接受肝移植的年龄为0.5-25.3岁(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Ig G升高。移植物组织学与急性排斥反应合并界面性肝炎或多或少兼容。所有病例均对糖皮质激素和硫唑嘌呤有反应。本组与其他有相似症状的儿童作为移植后自身免疫性肝炎(AIH)的研究对象。为了确定移植后AIH的抗原-抗体反应，对发病时或治疗后的血清与移植肝组织进行了组织交叉配对。虽然在胆管、门静脉和肝静脉内皮细胞有一定的抗原抗体反应，但在无新发AIH的病例中偶尔也能观察到类似的反应。反应的程度或位置各不相同。推测该病的发病机制可能与移植肝新生抗体的产生有关。另一例导管源性慢性排斥反应在胆管上皮细胞上有强烈反应，其识别、产生的时机和抗体产生的触发正在研究中，由于有报道认为De-novoAIH是慢性排斥反应的一种类型，与导管生成排斥反应的比较充满了意义。尽管针对从头AIH的特异性抗体的鉴定仍在进行中，但通过比较诱导性慢性排斥反应和从头AIH，有望阐明从头抗体在儿童肝移植中的作用，并有可能通过靶抗原的差异来区分这两种不同的发病机制。

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.