In the current study, we investigated whether Staphylococcus aureus grown from affected skin of atopic dermatitis (AD) patients secreted identifiable toxins that could act as allergens to induce IgE-mediated basophil histamine release. The secreted toxins of S. aureus grown from AD patients were identified by ELISA using antibodies specific for staphylococcal enterotoxin (SE) exfoliative toxin (ET), or toxic shock syndrome toxin (TSST-1). S. aureus isolates from 24 of 42 AD patients secreted identifiable toxins with SEA, SEB, and TSST accounting for 92% of the isolates. 32 of 56 AD sera (57%) tested contained significant levels of IgE primarily to SEA, SEB, and/ or TSST. In contrast, although SEA, SEB, or TSST secreting S. aureus could be recovered from the skin of psoriasis patients, their sera did not contain IgE antitoxins.Freshly isolated basophils from 10 AD patients released 5-59% of total histamine in response to SEA, SEB, or TSST-1 but only with toxins to which patients had specific IgE. Basophils from eight other AD patients and six normal controls who had no IgE antitoxin failed to demonstrate toxin-induced basophil histamine release. Stripped basophils sensitized with three AD sera containing IgE to toxin released 1541% of total basophil histamine only when exposed to the relevant toxin, but not to other toxins. Sensitization of basophils with AD sera lacking IgE antitoxin did not result in release of histamine to any of the toxins tested.These data indicate that a subset of patients with AD mount an IgE response to SEs that can be grown from their skin. These toxins may exacerbate AD by activating mast cells, basophils, and/or other Fce-receptor bearing cells armed with the relevant IgE antitoxin. (J. Clin. Invest. 1993Invest. . 92:1374Invest. -1380

It has been proposed that toxins and other bacterial protein products of Staphylococcus aureus can act as triggers or persistence factors in several inflammatory skin diseases. In this study, we examined the S. aureus isolates from the skin of patients with atopic dermatitis and psoriasis. We found that the bacterial isolates from these patients exhibited either characteristic superantigenic toxins or thermolabile toxins believed to be staphylococcal alpha-toxin. All of these staphylococcal strains also secreted extracellular staphylococcal protein A. We found significant differences in the action of these toxins on human keratinocytes and keratinocyte cell lines. The superantigenic toxins toxic shock syndrome toxin-1, staphylococcal enterotoxins A and B, and exfoliative toxin-A, as well as staphylococcal protein A, did not induce significant cytotoxic damage in the keratinocyte cell line HaCaT, whereas the staphylococcal alpha-toxin produced profound cytotoxicity. Keratinocyte cytotoxicity induced by staphylococcal alpha-toxin was time and concentration dependent and demonstrated the morphologic and functional characteristics of necrosis, not apoptosis. Addition of alpha-toxin to keratinocytes simultaneously induced cell lysis and tumor necrosis factor-alpha release into the medium within 30 min; apparently, it was constitutive tumor necrosis factor-alpha. On the other hand, superantigenic toxins and, in particular, protein A showed stimulation of tumor necrosis factor-alpha secretion in keratinocytes and release of this cytokine after 6-12 h of incubation. Thus, staphylococcal protein A, alpha-toxin, and superantigenic toxins found in S. aureus isolates from patients with psoriasis and atopic dermatitis can produce direct pro-inflammatory effects on keratinocytes through the release of tumor necrosis factor-alpha. We propose that these effects may be relevant to the induction and persistence of lesions in these two diseases.

This study augments our understanding of the potential role of S aureus exotoxins behaving as superantigens in the lateral wall of the nose in CHSwNP. Furthermore, local nasal IgE directed against these exotoxins may create a local allergic inflammation in the lateral wall of the nose. These two immunologic mechanisms are independent but may be additive in the inflammatory process in CHSwNP.

Kawasaki disease (KD) is an acute vasculitis of young children that can be complicated by coronary artery abnormalities. Recent findings suggest that a superantigen(s) may play an important role in stimulating the immune activation associated with the disease, although the origin of this superantigen(s) is unclear. Staphylococcus aureus, isolated from the rectum or pharynx of patients with KD, secretes toxic shock syndrome toxin 1 (TSST-1). The KD isolates express low levels of other exoproteins compared to isolates from patients with toxic shock syndrome (TSS). Thus, it was previously suggested that the KD isolates may be defective in the global regulatory locusagr (for accessory gene regulator), which positively regulates these factors (D. Y. M. Leung et al., Lancet 342:1385–1388, 1993). Here we describe another characteristic of KD isolates. When considered collectively, the KD isolates were found to express higher levels of staphylococcal protein A than the TSS isolates, another characteristic of an agr-defective phenotype. This correlated with a higher level of spa mRNA in these isolates. In contrast, the KD and TSS isolates expressed comparable levels of TSST-1, consistent with previous findings (D. Y. M. Leung et al., Lancet 342:1385–1388, 1993). Analysis of RNAIII transcript levels and nucleotide sequence analysis of the RNAIII-coding region suggested that the KD isolates are not defective in RNAIII, the effector molecule of the agrregulatory system. However, induction of RNAIII transcription in the KD isolates did not result in a dramatic decrease in the amount ofspa mRNA, as has been reported for other strains (F. Vandenesch, J. Kornblum, and R. P. Novick, J. Bacteriol. 173:6313–6320, 1991).

SummaryBackground-Bacterial infection with Staphylococcus aureus is a known trigger for the worsening of atopic dermatitis (AD). Staphylococcal superantigens have been theorized to potentially contribute to this worsening of AD seen with infection.