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 patients
are 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.