COMPARATIVE-STUDIES OF ANTIMITOCHONDRIAL AUTOANTIBODIES IN SERA AND BILE IN PRIMARY BILIARY-CIRRHOSIS

Primary biliary cirrhosis (PBC) is an autoimmune liver disease charact erized by destruction of intrahepatic bile ducts, Although the pathoge nesis of this disease is still unknown, high titers of antimitochondri al autoantibodies (AMA) have long been recognized in patient sera, How ever, little is known about the presence of AMA in bile, In this study , we investigated bile and sera from patients with PBC and healthy con trols for the presence of AMA and mitochondrial autoantigens, AMA were detected in the bile of 17 of 19 patients (89.4%) with PBC; they were specifically directed against the pyruvate dehydrogenase complex (PDC -E2) in 15 of 19 patients (78.9%), to the branched-chain 2-oxo-acid de hydrogenase complex E2 (BCOADC-E2) in 6 of 19 patients (31.6%), and to the 2-oxoglutarate dehydrogenase complex E2 (OGDC-E2) in 1 of 19 pati ents (5.3%), In a comparative study of sera from the same patients, an ti-PDC-E2 antibodies were found in 19 of 19 patients (100%), anti-BCOA DC in 9 of 19 patients (47.3%), and anti-OGDC-E2 in 4 of 19 patients ( 21.1%) patients, AMA in bile were always found together with antibodie s of corresponding specificities in the serum from the same patient, I mmunoglobulin (Ig)A AMA mere found in the bile of 9 of 19 patients (47 .7%) with PBC; they were specifically directed against PDC-E2 in 8 of 19 patients (42.1%) and to BCOADC in 2 of 19 patients (10.5%), Epitope mapping of IgA anti-PDC-E2 antibodies indicated that, like serum auto antibodies, the immunodominant epitope is directed against the inner l ipoyl domain of PDC-E2, The prevalence and antigen reactivity of IgA A MA in sera correlated completely with IgA AMA in bile, Autoantibodies against nuclear envelope pore proteins (gp210) were found in 1 of 8 (1 2.5%) sera of patients with PBC, but not in bile. Furthermore, and of particular interest, we detected the autoantigens, PDC-E2, OGDC-E2, an d ECOADC-E2, in the bile of 12 of 19 patients (63.2%), 9 of 19 patient s (47.4%), and 9 of 19 patients (47.4%), respectively; PDC-E2 was foun d in only 1 of 17 (5.9%) disease controls, Although the presence of AM A in bile may merely reflect the presence of these antibodies in sera, the simultaneous detection of mitochondrial autoantigens in bile sugg ests an increase of mitochondrial autoantigens at inflammatory sites, Such autoantigens, coupled with AMA, may augment the local immune resp onse and disease progression.