Autoimmune-mediated mechanism of biliary injury in primary biliary cirrhosis

原发性胆汁性肝硬变(PBC)被认为是一种自身免疫介导的肝内胆管损伤。对于疾病的免疫发病机制，进行了免疫遗传学分析和T细胞对自身抗原(胆汁蛋白B1-28和丙酮酸脱氢酶E2：PDHE2)的反应。1)免疫遗传学：DNA分型显示DR8是PBC发病的易感基因之一，DRB1^&lt；**&gt；0803在DR8的6个等位基因中出现频率最高。Tap-1、Tap-2和Dm基因的异质性也得到了研究，这些基因与人类白细胞抗原基因相近，既是免疫多肽向粗面内质网的转运体，又是免疫肽和MHC-II类复合体的稳定剂。(2)胆汁抗原：胆汁蛋白B1-28能刺激PBC患者的T细胞。氨基酸序列分析表明，该抗原与免疫球蛋白家族有部分同源性。以EB病毒转化的自体B细胞作为抗原提呈细胞，对从PBC患者外周血中建立的T细胞克隆进行鉴定。3)用2D免疫印迹法检测一种新的自身抗体：α-烯醇酶抗体。56例PBC患者中有16例检测到抗体，抗体阳性患者预后较抗体阴性患者差。

Primary biliary cirrhosis (PBC) is considered as an autoimmune mediated intrahepatic biliary injury. Regarding the immunopathogenesis of the disease, immunogenetical analysis and T cell responses to auto antigens (biliary protein B1-28, and pyruvate dehydrogenase E2 : PDHE2) were performed. Clinical significance of a new autoantibody against alpha enolase in PBC was also examined.1) Immunogenetics : DNA typing of HLA class I and II genes revealed that DR8 was one of susceptible genes to the development of the disease, and DRB1^<**>0803 was most frequent among 6 alleles of DR8. Heterogeneity of Tap-1, Tap-2 and DM genes which are locating close to HLA genes and function as transporter of immuno-peptides to rough ER and as stabilizer of immuno-peptide and MHC class II complexes, was also studied. Frequency of Bky2 (point mutant of Tap-2 allele type B) was significantly high in PBC,but DM genes examined was not, compared with control.2) Aotuantigen : Biliary protein B1-28 can stimulate T cells of PBC patients. Amino acid sequence analysis of the antigen showed partial homology with immuno-globulin family. Characterization of T cell clones which were established from peripheral lymphocytes of PBC patientsare under investigation, in which EBV transformed auto B cells were used as antigen presenting cells.3) A New autoantibody : alpha enolase antibody was detected with 2D western blotting. The antibody was detected in 16 of 56 PBC patients, and prognosis of the antibody positive patient was worse, compared with that of the antibody negative patients.