Why does GAS cause Acute Rheumatic Fever?
The classical explanation has been that the disease results from damaging immune responses to cross-reactive self-antigens following GAS infection (molecular mimicry) . The GAS cytoplasmic membrane is surrounded by an outer peptidoglycan layer covered by surface carbohydrates (Group A specific), proteins (M proteins), and glycoproteins. Immunoglobulins directed at alpha-helix motifs on M protein peptides can cross-react with cardiac myosin (although myosin is notably relatively absent in valvular tissue, and much damage in pathologic studies appears to be directed at collagen I and IV).
