Autoantibodies in the sera of patients with rheumatic heart disease: characterization of myocardial antigens by two-dimensional immunoblotting and N-terminal sequence analysis

The concept of antigenic mimicry in autoimmune diseases such as rheumatic f ever has been under investigation for decades and the range of cross-reacti ve tissue antigens for streptococcal-induced antibodies identified in rheum atic heart disease is still expanding. To identify heart tissue-reactive an tigens which may be implicated in the secondary immunopathogenesis of rheum atic fever, sera from 56 patients with acute rheumatic heart disease were p robed in two-dimensional Western blots for reactivity against heart tissue antigens. After two-dimensional immunoblot analysis, proteins were submitte d to N-terminal amino acid sequence analysis. This analysis identified crea tine kinase, two mitochondrial proteins and, at a low level, various stress proteins as cross-reactive myocardial antigens. Therefore, in addition to myosin, creatine kinase may represent another major antigen for autoreactiv e antibodies in rheumatic heart disease. Mitochondrial proteins have been i mplicated in the pathogenesis of inflammatory heart disease for some years, and in this study we have identified two mitochondrial proteins as relevan t antigens in rheumatic heart disease.