Role of staphylococcal superantigens in airway disease: a review, part 2: S-aureus enterotoxins in AERD, asthma, early childhood wheezing and COPD

Gram-positive Staphylococcus aureus germs constitutively have the possibility to release classical and egc locus-derived enterotoxins (SEs) which have superantigen activity, and effectively modify the functions of T- and B-cells, eosinophils, and other inflammatory and structural cells. The stimulation may lead to a TH2-polarized eosinophilic inflammation as well as a multiclonal IgE production, aggravating airway disease in the upper and lower respiratory tract. Recently, Staphylococcus aureus could be demonstrated to reside intraepithelially, and potentially to release superantigens into the tissue from within the epithelial cells. An immune defect, either in the innate or adaptive immunity, might be responsible for this phenomenon. Follicle-like structures and lymphocyte accumulations, specifically binding enterotoxins, can be found within the mucosal tissue. Interestingly, also IgE antibodies to enterotoxins can be found in the majority of aspirin-sensitive patients, in nasal polyps and severe asthma alike. We here summarize the current evidence from animal and human studies for an active role of SEs in allergic rhinitis, nasal polyps, asthma, COPD and, finally, early childhood wheezing, and discuss the similarities between those disease manifestations. As a principle, the occurrence of IgE antibodies to SEs correlates to disease severity in terms of total IgE formation, inflammatory markers and clinical expression of disease. Preliminary evidence from animal models underlines the high potency of SEs to induce or modulate disease, and a few pilot intervention trials may serve as proof of concept for the impact of SEs on disease severity. However, therapeutic approaches are so far limited and empirical, and need further improvement to tackle this currently underestimated clinical challenge