Streptococcus pyogenes generally inhabits epithelial surfaces, especially of the throat and skin, but it can cause severe conditions, including rheumatic fever, which is a serious autoimmune sequela of pharyngitis (5). The onset of rheumatic fever usually occurs about two to four weeks after a streptococcal throat infection. It is estimated that around 30 million people are currently affected by rheumatic heart disease globally (6), with 300,000 deaths each year, of which 60% occurred prematurely.
Rheumatic fever is a classic example of molecular mimicry where S. pyogenes M‐protein shares an α‐helical coiled structure similar to a heart protein (e.g., myosin). The antibodies from patients with acute rheumatic fever (ARF) cross‐react with both M‐protein and the cardiac tissue (7). Variability in the N-terminal of M proteins generates distinct M serotypes which makes it difficult to make a vaccine with good protection. Of the more than 130 M-protein types identiﬁed, M types such as 1, 3, 5, 6, 14, 18, 19, and 24 have been associated with rheumatic fever (8).
Moreover, some antibodies recognize the N-acetyl-β-Dglucosamine (GLcNAc) of S. pyogenes and cross-react with myosin (9). Besides, S.pyogenes induces the production of collagen IV autoantibodies after that S. pyogenes binds to collagen IV, a major component of subendothelial basement membranes, intermediated by a collagen-binding octapeptide motif of M-protein (10). Cross-reactivity has been found of anti S.pyogenes antibodies with vimentin, laminin, tropomyosin (11), and fibronectin (12).
Even when comprehensive studies on ARF and autoantibodies exist, there is currently no single test to diagnose or prevent this disease. Diagnosis of ARF is done using clinical criteria (Jones criteria) and excluding other differential diagnostics. Possible future research areas may include a better understanding of the epidemiology of the disease to improve diagnosis and identify new avenues for therapeutic intervention and development of group A streptococcal vaccine.