Novel Staphylococcal Superantigens in Children with Kawasaki Disease

Abstract

The aetiology of Kawasaki disease (KD), particularly the role of superantigens, remains controversial. We have investigated the presence of all reported staphylococcal superantigens in KD patients and healthy controls. Methods 87 children with KD and 57 similarly aged healthy children undergoing routine vaccination were screened by bacterial nasal swabs for the presence of superantigen-producing Staphylococcus aureus. A specifically developed T-cell proliferation assay detected mitogenic activity in sterile bacterial culture supernatants, indicative of superantigen activity. The presence of the S. aureus-specific nuc gene and genes for all reported staphylococcal superantigen toxins (i.e. toxic shock syndrome toxin-1, staphylococcal enterotoxins (SE) A, B, C, D, E, H, K, the enterotoxin gene cluster (egc) toxins G, I, K, L and M, as well as exfoliative toxins (ExT) A and B) were detected in DNA from bacterial cultures by PCR. Results A similar proportion of KD patients and controls (~25%) had nasal colonisation with S. aureus. Mitogenic activity was observed in 25 (29%) of S. aureus nasal isolates from KD patients versus 4 (7%) of isolates from controls (p<0.005). S. aureus DNA encoding superantigen genes or mitogenic activity was present in 28 (32%) of KD isolates, but only 9 (16%) of controls (p<0.05). Discussion Although S. aureus nasal carriage is not increased in KD patients, the presence of staphylococcal superantigens, detected by both bioassay and genomic sequence analysis, strongly supports an aetiological role for superantigens in KD. Moreover these data suggest that any one of a number of different superantigen toxins, produced by S. aureus or possibly by other bacteria, viruses or mycoplasma, can cause KD. This might explain why efforts to find an unifying aetiological association, or a consistent T cell receptor Vβ repertoire, have so far proved unsuccessful.