Epitope mapping of the branched chain α-ketoacid dehydrogenase dihydrolipoyl transacylase (BCKD-E2) protein that reacts with sera from patients with idiopathic dilated cardiomyopathy

Aftab A. Ansari, Nicolas Neckelmann, Francois Villinger, Patrick S Leung, Dean J. Danner, Sukhdev S. Brar, Shuping Zhao, Michael B. Gravanis, Ann Mayne, M. Eric Gershwin, Ahvie Herskowitz

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Abstract

Sera from 29 of 48 patients with idiopathic dilated cardiomyopathy (IDCM) and six of six patients with dilated cardiomyopathy (DCM) secondary to suspected viral myocarditis were shown to react with the branched chain α- ketoacid dehydrogenase (BCKD) complex mitochondrial proteins. Whereas sera from only 1 of 26 patients with ischemic heart disease showed reactivity against the BCKD complex protein, 0 of 30 sera from normal human volunteers, 0 of 64 sera from patients with lupus, and 0 of 34 sera from patients with rheumatoid arthritis showed detectable reactivity, denoting an element of specificity for the reactivity of sera from IDCM patients. The major reactivity was localized to the dihydrolipoyl transacylase (E2) component of BCKD complex. By using recombinant techniques, the immunodominant BCKD-E2 epitope recognized by sera from IDCM patients was localized to amino acid (aa) sequences 116 to 134. Each of the IDCM sera that reacted with the native BCKD complex was shown to react with the immunodominant peptide, as defined by a peptide inhibition ELISA and by an ELISA using the reactive peptide conjugated to BSA. Sera from IDCM patients that reacted with the native BCKD complex and the reactive peptide also showed inhibition of BCKD enzyme activity. The possible mechanisms for the induction of the Abs and the implications of these findings for the pathogenesis of IDCM are discussed.

Original languageEnglish (US)
Pages (from-to)4754-4765
Number of pages12
JournalJournal of Immunology
Volume153
Issue number10
StatePublished - Nov 15 1994

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ASJC Scopus subject areas

  • Immunology

Cite this

Ansari, A. A., Neckelmann, N., Villinger, F., Leung, P. S., Danner, D. J., Brar, S. S., Zhao, S., Gravanis, M. B., Mayne, A., Gershwin, M. E., & Herskowitz, A. (1994). Epitope mapping of the branched chain α-ketoacid dehydrogenase dihydrolipoyl transacylase (BCKD-E2) protein that reacts with sera from patients with idiopathic dilated cardiomyopathy. Journal of Immunology, 153(10), 4754-4765.