A superantigen hypothesis for the pathogenesis of chronic hyperplastic sinusitis with massive nasal polyposis

Background: The pathogenesis of chronic hyperplastic sinusitis with massive nasal polyposis is still an enigma; however, the molecular biology of this disease is beginning to become unraveled and the proinflammatory cytokines and the message and the product of these cytokines have all been identified in nasal polyps. However, the initial trigger that causes inflammation of the lateral wall of the nose to up-regulate lymphocytes and eosinophils is still unknown. Methods: Thirteen patients with massive polyposis were studied. The mucus of the nasal cavities surrounding the nasal polyps was studied for both bacterial and fungal species. The lymphocytes of the nasal polyps were extracted and evaluated for the T-cell receptor, particularly, the variable beta region of this receptor. Enterotoxins (superantigens) of the bacteria were studied. Finally, the histopathology of nasal polyps was studied. Results: Fifty-five percent of the patients had toxin-producing Staphylococcus aureus in the nasal mucus adjacent to the polyps. Three different enterotoxins were isolated, including Staphylococcus enterotoxin A, Staphylococcus enterotoxin B, and toxic shock syndrome toxin 1. The variable B specificity for these superantigens was identified also in the polyp lymphocyte T-cell receptor. Conclusion: A superantigen hypothesis for massive polyposis is suggested because the most common bacterial species found in the nasal mucus is Staphylococcus aureus. These bacteria produce enterotoxins in all of the cases studied and the corresponding variable P region of the T-cell receptor also was up-regulated in the polyp lymphocytes in cases studied thus far. These data taken together suggest that the initial injury to the lateral wall of the nose may be the result of toxin-producing Staphylococci. Superantigens (enterotoxins) may up-regulate lymphocytes to produce cytokines that are responsible for the massive up-regulation of lymphocytes, eosinophils, and macrophages, the three most common inflammatory cells found in massive nasal polyposis.