No compelling evidence that vaccination with Streptococcus pyogenes group A carbohydrate elicits cross-reactive rheumatic fever autoantibodies
Over the past seventy years, researchers have examined the specificity of anti-group A carbohydrate (GAC) monoclonal and polyclonal antibodies, as well as antibodies raised against other components of Streptococcus pyogenes that react with GAC. Findings suggest that some autoantibodies associated with rheumatic fever recognize the N-Acetyl-β-D-glucosamine side chains of GAC and may cross-react with human tissues. However, this cross-reactivity appears to be a result rather than the cause of autoimmunity.
“We propose that the group A carbohydrate (GAC) should be further considered as a broadly protective antigen for a group A streptococcal vaccine.”
Background: Rising concern of Streptococcus pyogenes infections
Streptococcus pyogenes, also known as group A streptococcus (GAS), represents a growing health concern worldwide. The increase in invasive GAS disease across several countries coincides with a heavy global burden of its autoimmune sequelae.
Repeated GAS infections can provoke acute rheumatic fever (ARF), particularly in regions where these infections are endemic due to socioeconomic disadvantages. ARF primarily manifests through rheumatic carditis and Sydenham’s chorea, both autoimmune diseases involving antibodies and immune cells that mistakenly target human antigens in the heart and brain.
Susceptibility factors
Despite high infection rates in endemic areas, only a fraction of individuals develop ARF. This pattern likely reflects genetic predisposition to autoimmune reactions following GAS infection.
Conclusion
Current evidence indicates that while antibodies against GAC can cross-react with human tissues, they are not the primary cause of autoimmune disease. Continued research on GAC could inform safer and broader vaccine development against group A streptococcal infections.
Author’s summary: The reviewed research suggests GAC-based vaccines may offer protective potential against Streptococcus pyogenes without provoking harmful autoimmune responses.