Overall Picture of an Emerging Neonatal Infectious Disease Induced by A Superantigenic Exotoxin Mainly Produced by Methicillin-Resistant Staphylococcus Aureus

Since 1992, many neonates in neonatal intensive care units in Japan have been developing fever and systemic exanthema. Immunological analyses of neonates with these symptoms has revealed that the bacterial superantigen, toxic shock syndrome toxin-1 (TSST-1) is the cause. The name neonatal TSS-like exanthematous disease (NTED) has been applied to this condition. The most striking clinical finding has been that none of the term neonates have developed shock or died of NTED. The timing of NTED epidemics has coincided with the spread of emerging TSST-1-producing methicillin-resistant Staphylococcus aureus clones in Japan. The low frequency of pregnant women with positive anti-TSST-1 antibody titers could be one reason for the spread of NTED in Japan. Neonates have immune tolerance against TSST-1 and may actively suppress the immune response to NTED with interleukin-10. According to the T cell responses in infants or young children with diseases induced by TSST-1, the pathophysiology of TSST-1-related diseases may be age-dependent. The precise mechanism of anergy and deletion of specific T cells stimulated with TSST-1 should be investigated in neonates infected with NTED. Both NTED and TSS might provide good models for analyzing the mechanism(s) of neonatal immune tolerance and the age-dependence of human immunity. This disease has not only become representative of diseases caused by superantigens, but has also yielded a considerable amount of evidence about human immune reactions against superantigens.