The mechanisms of intrinsic or non-allergic asthma remain uncertain as allergens have no obvious role in driving the inflammatory process in the airways. However, IgE synthesis occurs in the airways, despite negative skin prick tests and serum-specific IgE. Furthermore, the inflammatory process in the airways is very similar between allergic and non-allergic asthma, with increased T-helper type 2 (Th2) cells, mast cell activation and infiltration of eosinophils. This pattern of inflammation is associated with a similar expression of inflammatory mediators, including Th2 cytokines and eosinophilotactic chemokines. There is increasing evidence that microbial superantigens, particularly Staphylococcal enterotoxins are important in amplifying inflammation in atopic dermatitis and chronic rhinosinusitis, in atopic and non-atopic patients. Superantigens may also be important in intrinsic asthma as airway epithelial cells may be colonized by Staphylococci and other superantigen-producing microbes. Superantigens produced locally in the airways may lead to class switching of local B cells, resulting in polyclonal IgE production in the airways and also specific IgE against the superantigen (which functions as a ‘superallergen’). This leads to sensitization of mast cells, which can be activated by the usual asthma triggers, such as exercise. Superantigens also cause clonal expansion of T cells, resulting in increased Th2 cells and CD8+ cells, while suppressing regulatory T cells. Superantigens may also reduce responsiveness to corticosteroids, resulting in more severe asthma. Finally, cytotoxic autoantibodies may also be implicated as IgG antibodies directed against epithelial proteins, such as cytokeratin-18, have been detected in intrinsic asthma, possibly as a result of epithelial damage and this may make epithelial cells more susceptible to microbial colonization. The therapeutic implications are that antibodies against local IgE and microbial superantigens or antibiotic therapy to eradicate the relevant superantigen-producing microorganisms may improve the efficacy of conventional therapy with corticosteroids.
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