Immunoreactivity of antimitochondrial autoantibodies in Japanese patients with primary biliary cirrhosis.
The incidence and prevalence of primary biliary cirrhosis show wide geographic differences. The frequency of this disease in Japan is lower than in Northern Europe. To elucidate the immunoreactivity of serum with enzymes of the 2-oxo-acid dehydrogenase complex (2-OADC) and the M2 mitochondrial antigenic complex in Japanese patients, we examined sera from 107 patients with primary biliary cirrhosis from three geographically different regions of Japan. The sera were assayed by immunofluorescence on frozen tissue sections, immunoblotting on bovine heart mitochondria and recombinant E2 subunit of branched chain oxo-acid dehydrogenase complex (BCOADC-E2), ELISA using recombinant E2 subunit of human pyruvate dehydrogenase complex (PDC-E2) and purified porcine 2-oxoglutarate dehydrogenase complex (OGDC), and enzyme inhibition assay using procine PDC and OGDC. Of the 107 sera, 95 (88%) reacted by immunofluorescence, 102 (95%) by immunoblotting with at least one of the M2 autoantigens, although only 78 (73%) reacted with PDC-E2; 72 (67%) by ELISA with PDC-E2; and 81 (76%) with PDC by the enzyme inhibition assay. Thus, the frequency of reactivity with PDC-E2 by all assays was lower for Japanese than the reported frequency for Caucasian patients with primary biliary cirrhosis, whereas the frequency of reactivity by immunoblotting and ELISA against 2-OADC enzymes other than PDC was relatively higher. The relative frequency of reactivity of autoantibodies to the M2 autoantigens was similar for the three different regions of Japan. The different autoantibody profiles for Japanese and Caucasian patients with primary biliary cirrhosis point to immunogenetic and environmental determinants of this disease, which should provide new insights into its autoimmune origins.
Omagari
K
K
Centre for Molecular Biology and Medicine, Monash University, Clayton, Victoria, Australia.
Rowley
M J
MJ
Jois
J A
JA
Feeney
S J
SJ
Komatsu
K
K
Maeda
T
T
Onishi
S
S
Yamazaki
K
K
Suzuki
K
K
Galperin
C
C
Mackay
I R
IR
D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007564:Japan; D007658:Ketone Oxidoreductases / Q000276:immunology* / Q000378:metabolism; D008105:Liver Cirrhosis, Biliary / Q000097:blood / Q000208:ethnology / Q000276:immunology*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000276:immunology*; D009097:Multienzyme Complexes / Q000276:immunology* / Q000378:metabolism; D011768:Pyruvate Dehydrogenase Complex / Q000276:immunology* / Q000378:metabolism
D001323:Autoantibodies; D009097:Multienzyme Complexes; D011768:Pyruvate Dehydrogenase Complex; D007658:Ketone Oxidoreductases; D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)