A superantigen hypothesis for the pathogenesis of chronic hypertrophic rhinosinusitis, allergic fungal sinusitis, and related disorders.

BACKGROUND

Chronic eosinophilic-lymphocytic respiratory mucosal inflammatory disorders include hypertrophic sinus disease, allergic fungal sinusitis, allergic bronchopulmonary aspergillosis, and chronic severe asthma. They have many analogous or shared aspects of pathology at molecular, cellular, and clinical levels of analysis.

OBJECTIVE

To propose a theory, and supporting data through comprehensive literature review, that unifies these diseases' pathogenesis. METHODS AND DATA SOURCES: Current medical literature was used as supportive background information. Reinterpretation of existing studies and reasoned speculation were used when necessary and identified where used. English language MEDLINE articles that referenced sinusitis, rhinosinusitis, allergic fungal sinusitis, asthma, allergic bronchopulmonary aspergillosis, nasal polyp, superantigen, and T cell receptor from 1983 to present were potentially used as background or supportive information. Additional referenced articles, published abstracts, and National Center for Biotechnology Information Entrez protein database searches were used. Case reports, studies, review articles, and textbooks were included.

RESULTS

Multiple lines of evidence support the proposed hypothesis that microbial T cell superantigen production, persistence, and host-responsiveness are the fundamental components that unify the pathogenesis of all common chronic eosinophilic-lymphocytic respiratory mucosal inflammatory disorders. Superantigen amplification of preexisting immunopathology is the proposed mechanism for disease induction and maintenance. Preexisting immunopathology is created in the individual by a potential heterogeneity of immunopathologic signals that can include type I immediate hypersensitivity, other antigen-specific immune responses, cytokine dysregulation, eicosanoid dysregulation, various genetic mutations, and other molecular pathology. Although the ability to develop chronic severe inflammatory disease is dependent upon this immunopathology, host T cell receptor V beta genetics and persistent superantigen production/exposure at the respiratory mucosa by relevant superantigen-producing extra- or intracellular microbes are postulated to be required. This mechanism for disease pathogenesis may also apply to other disorders. Approaches to prove this theory and its predictions are presented.

CONCLUSIONS

The pathogenesis of all the disorders discussed can be unified through the superantigen hypothesis proposed. Multiple lines of evidence support this hypothesis. How we view these common conditions will change, and new research into pathogenesis and treatment will occur if this proves true.