Journal of Hepatology 1994; 21:673-677 Pr#lted hz Denmark. All rights reserved Munksgaard. Copenhagen Copyright © Journalof Hepatology 1994 Journal of Hepatology ISSN 0168-8278 Rapid Publication Cross-reactivity of anti-Mycobacteriumgordonae antibodies with the major mitochondrial autoantigens in primary biliary cirrhosis Lidia Vilagut l, Jordi Vila l, Odette Vifias 2, Albert Par6s 3, Angels Gin6s 3, Maria Teresa Jim6nez de Anta l and Joan Rod6s 3 ILaboratorv of Microbiology, 2Servei d'hnmunologia and 3Liver Unit, Hospital Clinic i Provincial, Universit.v of Barcelona, Barcelona, Spain (Received 30 December 1993) Primary biliary cirrhosis is a chronic cholestatic liver disease associated with autoimmune disorders. Antimitochondrial autoantibodies and granulomatous portal lesions are characteristic in primary biliary cirrhosis. Since granuloma may be induced by Mycobacteria, and there is evidence implicating Mycobacteria as infectious agents capable of initiating autoim- munity, a study was performed to determine the presence of antibodies against 10 atypical Mycobacteria in 19 patients with primary biliary cirrhosis, and in 35 controls (25 patients with other chronic liver diseases and 10 healthy subjects). All primary biliary cirrhosis sera.and none of the controls reacted with the extract from Mycobacterium gordonae, showing identical recognition profiles with two polypeptides of 70-65 and 55 kDa. No other reaction was found in primary biliary cirrhosis patients and in controls with the extracts from the other nine atypical Mycobacteria tested. Eluted immunoglob- ulins which reacted with the 70-65 and 55 kDa polypeptides from M. gordonae, bound to the mitochondrial antigens PDH-E2 and BCKDH-E2. Furthermore, when the extract from M. gordonae was tested with eluted immunoglobulins from recognized PDH-E2 and BCKDH-E2 by primary biliary cirrhosis patients, we observed both 70-65 and,55 kDa polypeptides. These data indicate that antibodies to M. gordonae, found in all primary biliary cirrhosis patients, cross- react with the major mitochondrial targets of the disease. We suggest that M. gordonae may play a potential pathogenic role in primary biliary cirrhosis. © Journal of Hepatology. Key words: Antimitochondrial autoantibodies; Autoimmunity; Molecular mimicry; Mycobacterial components Primary biliary cirrhosis (PBC) is a chronic cholestastic liver disease of unknown etiology. The pathogenesis of PBC is considered autoimmune because of the presence of many immunological abnormalities, and its association with other autoimmune disorders. The most fascinating fact is that practically all PBC patients present antimito- chondrial autoantibodies which, on immunoblots, recog- nize five antigens from the mitochondrial multienzymatic complex named alpha-ketoacid dehydrogenase complex, at apparent molecular weights of 75-70, 56, 51, 45 and 36 kDa (1). The 75-70 kDa antigen has been identified as the dihydrolipoamide acetyltransferase (E2) of the pyruvate dehydrogenase complex (PDH-E2), the 51 kDa antigen corresponds to the E2 of the branched chain alpha-ke- toacid dehydrogenase complex (BCKDH-E2), or to the E2 of the alpha-ketoglutarate dehydrogenase complex (a- KGDH). The 56 kDa antigen is designated as protein X, a component of the PDH (PDH-X) and the remaining two antigens of 45 and 36 kDa are the alpha-subunit and the beta-subunit, respectively, of the pyruvate dehydrogen- ase (El) from the pyruvate dehydrogenase complex. Previous work showed that sera from PBC patients re- act with a wide spectrum of prokaryotes, including E. coli (2). Despite these studies, up to now there has been no definite evidence that a specific infectious agent may be the precipitating mechanism initiating bile duct lesions. Correspondence to: Joan Rod6s MD, Liver Unit, Hospital Clinic i Provincial,C/Villarroel 170, 08036 Barcelona,Spain.