Antibody levels to the class I and II epitopes of the M protein and myosinare related to group A streptococcal exposure in endemic populations

Rheumatic fever (RF)/rheumatic heart disease (RHD) and post-streptococcal g lomerulonephritis are thought to be autoimmune diseases, and follow group A streptococcal (GAS) infection. Different GAS M types have been associated with rheumatogenicity or nephritogenicity and categorized into either of tw o distinct classes (I or II) based on amino acid sequences present within t he repeat region ('C' repeats) of the M protein. Sera from ARF patients hav e previously been shown to contain elevated levels of antibodies to the cla ss I-specific epitope and myosin with the class I-specific antibodies also being cross-reactive to myosin, suggesting a disease association. This stud y shows that immunoreactivity of the class I-specific peptide and myosin do es not differ between controls and acute RF (ARF)/RHD in populations that a re highly endemic for GAS, raising the possibility that the association is related to GAS exposure, not the presence of ARF/RHD. Peptide inhibition st udies suggest that the class I epitope may be conformational and residue 10 of the peptide is critical for antibody binding. We demonstrate that corre lation of antibody levels between the class I and II epitope is due to clas s II-specific antibodies recognizing a common epitope with class I which is contained within the sequence RDL-ASRE. Our results suggest that antibody prevalence to class I and II epitopes and myosin is associated with GAS exp osure, and that antibodies to these epitopes are not an indicator of diseas e nor a pathogenic factor in endemic populations.