Variations in the protective immune response against streptococcal superantigens in populations of different...

Superantigens (SAgs) from group A streptococcus (GAS) are potent T cell mitogens, and have been suggested to play a role in severe streptococcal disease. Neutralizing antibodies protect against SAg-mediated disease and their levels should therefore be inversely related to severe streptococcal infection. Neutralizing anti-SAg titers in patients with severe GAS infection and patients without disease were compared in two separate groups. The first group comprised patients with invasive GAS disease from New Zealand European, Maori, and Pacific Island descent. The second group comprised Aboriginal Australian individuals with rheumatic heart disease and/or a past history of acute rheumatic fever. Patients sera were tested for their ability to neutralize T cell mitogenicity of recombinant streptococcal SAgs as a measure of functional SAg-neutralizing antibody concentration. In both studies, no inverse correlation was observed between disease and the level of serum SAg-neutralizing activity. Notably, much higher levels of natural immunity to all streptococcal SAgs were found in New Zealand Maori, New Zealand Pacific Island, and Aboriginal Australian individuals, suggesting a high degree of natural exposure and seroconversion in these groups compared to the New Zealand European cohort. Levels of serum antibodies against SAgs could not be used to predict disease susceptibility in groups with existing high levels of SAg-neutralizing antibodies.