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

• Published in: International immunology Vol. 13; no. 10; pp. 1335 - 1343
• Main Authors: Brandt, Evelyn R., Yarwood, Penny J., McMillan, David J., Vohra, Harpreet, Currie, Bart, Mammo, Layla, Pruksakorn, Sumalee, Saour, J., Good, Michael F.
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.10.2001; Oxford Publishing Limited (England)
• Subjects: Acute Disease; AM protein; Amino Acid Sequence; antibodies; Antibodies, Bacterial - blood; Antibody Specificity; Antigens, Bacterial - immunology; ARF acute rheumatic fever; Australia - epidemiology; autoimmunity; Bacterial Outer Membrane Proteins - immunology; Carrier Proteins - immunology; Endemic Diseases; Epitope Mapping; Epitopes; GAS group A streptococcal; Histocompatibility Antigens Class I; Histocompatibility Antigens Class II; Humans; India - epidemiology; infectious immunity bacteria; Molecular Sequence Data; myosin; Myosins - immunology; Oceanic Ancestry Group; Peptides - immunology; Prevalence; RF rheumatic fever; RHD rheumatic heart disease; Rheumatic Fever - epidemiology; Rheumatic Fever - immunology; Rheumatic Heart Disease - etiology; Rheumatic Heart Disease - immunology; Saudi Arabia - epidemiology; Streptococcal Infections - etiology; Streptococcal Infections - immunology; Streptococcus pyogenes; Streptococcus pyogenes - immunology; Thailand - epidemiology; Saudi Arabia; Australia; Thailand; India
• ISSN: 0953-8178; 1460-2377
• DOI: 10.1093/intimm/13.10.1335

Rheumatic fever (RF)/rheumatic heart disease (RHD) and post-streptococcal glomerulonephritis 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 two distinct classes (I or II) based on amino acid sequences present within the repeat region (`C' repeats) of the M protein. Sera from ARF patients have previously been shown to contain elevated levels of antibodies to the class I-specific epitope and myosin with the class I-specific antibodies also being cross-reactive to myosin, suggesting a disease association. This study shows that immunoreactivity of the class I-specific peptide and myosin does not differ between controls and acute RF (ARF)/RHD in populations that are highly endemic for GAS, raising the possibility that the association is related to GAS exposure, not the presence of ARF/RHD. Peptide inhibition studies suggest that the class I epitope may be conformational and residue 10 of the peptide is critical for antibody binding. We demonstrate that correlation of antibody levels between the class I and II epitope is due to class 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 exposure, and that antibodies to these epitopes are not an indicator of disease nor a pathogenic factor in endemic populations.