EPITOPE MAPPING OF THE BRANCHED-CHAIN ALPHA-KETOACID DEHYDROGENASE DIHYDROLIPOYL TRANSACYLASE (BCKD-E2) PROTEIN THAT REACTS WITH SERA FROM PATIENTS WITH IDIOPATHIC DILATED CARDIOMYOPATHY

Sera from 29 of 48 patients with idiopathic dilated cardiomyopathy (ID CM) and six of six patients with dilated cardiomyopathy (DCM) secondar y to suspected viral myocarditis were shown to react with the branched chain alpha-ketoacid dehydrogenase (BCKD) complex mitochondrial prote ins. Whereas sera from only 1 of 26 patients with ischemic heart disea se showed reactivity against the BCKD complex protein, 0 of 30 sera fr om normal human volunteers, 0 of 64 sera from patients with lupus, and 0 of 34 sera from patients with rheumatoid arthritis showed detectabl e reactivity, denoting an element of specificity for the reactivity of sera from IDCM patients. The major reactivity was localized to the di hydrolipoyl transacylase (E2) component of BCKD complex. By using reco mbinant techniques, the immunodominant BCKD-E2 epitope recognized by s era from IDCM patients was localized to amino acid (aa) sequences 116 to 134. Each of the IDCM sera that reacted with the native BCKD comple x was shown to react with the immunodominant peptide, as defined by a peptide inhibition ELISA and by an ELISA using the reactive peptide co njugated to BSA. Sera from IDCM patients that reacted with the native BCKD complex and the reactive peptide also showed inhibition of BCKD e nzyme activity. The possible mechanisms for the induction of the Abs a nd the implications of these findings for the pathogenesis of IDCM are discussed.