title: 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.
abstract: 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.
authors.affiliation: CRC for Vaccine Technology, The Queensland Institute of Medical Research, PO Royal Brisbane Hospital, and the Australian Centre for International and Tropical Health and Nutrition, University of Queensland, Brisbane 4029, Australia.
authors.forename: E R
authors.initials: ER
authors.lastname: Brandt
authors.forename: P J
authors.initials: PJ
authors.lastname: Yarwood
authors.forename: D J
authors.initials: DJ
authors.lastname: McMillan
authors.forename: H
authors.initials: H
authors.lastname: Vohra
authors.forename: B
authors.initials: B
authors.lastname: Currie
authors.forename: L
authors.initials: L
authors.lastname: Mammo
authors.forename: S
authors.initials: S
authors.lastname: Pruksakorn
authors.forename: J
authors.initials: J
authors.lastname: Saour
authors.forename: M F
authors.initials: MF
authors.lastname: Good
mesh_terms: D000208:Acute Disease; D000595:Amino Acid Sequence; D000907:Antibodies, Bacterial / Q000097:blood; D000918:Antibody Specificity; D000942:Antigens, Bacterial / Q000276:immunology; D001315:Australia / Q000453:epidemiology; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology*; D019353:Endemic Diseases; D018604:Epitope Mapping; D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D006801:Humans; D007194:India / Q000453:epidemiology; D008969:Molecular Sequence Data; D009218:Myosins / Q000276:immunology*; D010455:Peptides / Q000276:immunology; D015995:Prevalence; D012213:Rheumatic Fever / Q000453:epidemiology / Q000276:immunology; D012214:Rheumatic Heart Disease / Q000209:etiology / Q000276:immunology; D012529:Saudi Arabia / Q000453:epidemiology; D013290:Streptococcal Infections / Q000209:etiology / Q000276:immunology*; D013297:Streptococcus pyogenes / Q000276:immunology*; D013785:Thailand / Q000453:epidemiology
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D010455:Peptides; C014689:streptococcal M protein; D009218:Myosins