Background: Group A Streptococcus (GAS) causes superficial pharyngitis and skin infections as well as serious autoimmune sequelae such as acute rheumatic fever (ARF). ARF can progress to chronic rheumatic heart disease that is associated with significant morbidity and mortality in low- and middle-income countries, as well as in Māori and Pacific communities within New Zealand. ARF pathogenesis remains poorly understood. Immune priming by repeated GAS infections is thought to trigger ARF, and there is growing evidence for the role of skin infections in this process.
Methods: We utilised our recently developed 8-plex immunoassay, comprising antigens used in clinical serology for the diagnosis of ARF (SLO, DNase B, SpnA), and five conserved prospective GAS vaccine antigens (Spy0843, SCPA, SpyCEP, SpyAD, Group A carbohydrate), to characterise antibody responses in sera from New Zealand children with a range of clinically diagnosed GAS disease; ARF (n=79), GAS-positive pharyngitis (n=94), GAS-positive skin infection (n=51) and matched healthy controls (n=90).
Results: The magnitude and breadth of antibodies in ARF was very high, giving rise to a distinct serological profile. An average of 6.5 antigen‑specific reactivities per individual was observed in ARF, compared to 4.2 in skin infections and 3.3 in pharyngitis.
Conclusions: ARF patients have a unique serological profile, which may be the result of repeated precursor pharyngitis and skin infections that progressively boost antibody breadth and magnitude.