Streptococcal Superantigens and Their Role in the Pathogenesis of Severe Infections

Group A streptococci (GAS), produce a large number of extracellular proteins which contribute to virulence, among these are the streptococcal pyrogenic exotoxins (spe), SpeA, SpeB, SpeC, and the recently identified SpeF and streptococcal superantigen SSA. The streptococcal as well as the staphylococcal exotoxins have all been shown to belong to the rapidly growing group of microbial proteins designated superantigens because of their potency to stimulate massive T-cell proliferation and subsequent release of large amounts of cytokines. Production of cytokines constitute an important part of the host defense against infectious agents; however, at high concentrations these immunomodulatory substances can be harmful. The superantigens have been implied in the pathogenesis of staphylococcal and streptococcal induced toxic shock and the host humoral response against the Spe's have been shown to be of importance for the clinical manifestation of streptococcal infection. Patients who developed severe streptococcal infections had significantly lower levels of serum antibodies with the ability to neutralize SpeB and SpeF induced mitogenicity than did patients who developed uncomplicated streptococcal tonsillitis, even though the majority of the patients had high Spe specific ELISA serum titers. Recent studies have shown successful treatment of streptococcal toxic shock through early administration of intravenous gamma globulin with high antibody titers against the Spe toxins. The future studies will have to be directed towards the identification of mitogen neutralizing epitopes of the different toxins in order to develop more efficient immunoglobulin preparations.