Further Observations on the Role of Staphylococcus aureus Exotoxins and IgE in the Pathogenesis of Nasal Polyposis

Objectives/Hypothesis: Recent studies have suggested that Staphylococcus aureus secrete exotoxins that may act as superantigens and upregulate the variable beta region of lymphocytes in chronic hyperplasticsinusitis with nasal polyposis (CHSwNP). The aim of this study was to add further information for correlating the presence of staphylococcal species and the upregulation of the V-beta region of both nasal polyp lymphocytes and peripheral blood lymphocytes. Furthermore, IgE-mediated hypersensitivity directed against these exotoxins produces an additional independent immunologic mechanism in upregulating the inflammatory response in the lateral wall of the nose in nasal polyposis. Study Design: Prospective study. Methods: Nasal polyps were harvested from 38 patients with CHSwNP. Eleven patients were studied for the correlation of exotoxin from staphylococcal species and the variable beta region of lymphocytes in both the nasal polyp lymphocytes and corresponding peripheral blood lymphocytes. Eight additional patients with CHSwNP were studied for local and systemic IgE-mediated immunity directed against S aureus exotoxins. Flow cytometry was used to analyze the V-beta repertoire of polyp-derived CD3-positive lymphocytes from 11 patients. S aureus was isolated from nine patients, and coagulase-negative Staphylococcus was isolated from two patients in whom at least 1 x 10(6) T cells could be isolated from their nasal polyps. A quantitative assay for IgE was developed to study the levels of this immunoglobulin directed against S aureus exotoxins in both the nasal polyp and the peripheral blood lymphocytes of 11 patients and in the nasal mucus and serum of eight additional patients. Results: Eleven patients had T-cell V-beta clonal expansion. S aureus exotoxin upregulated the corresponding V-beta region of lymphocytes in both the nasal polyp T cells as well as the T cells from the peripheral blood in nine patients, and two patients with coagulase-negative Staphylococcus also demonstrated upregulation of the V-beta region in the nasal polyps in the absence of exotoxins. In one patient, in vivo exotoxin was isolated, which correlated with the in vitro isolation from the organism itself. IgE directed against staphylococcal enterotoxin B (SEB) and toxic shock syndrome toxin was significantly elevated in the sera of patients with CHSwNP (P < .0001) as compared with the sera of age-related healthy control subjects; IgE directed against staphylococcal enterotoxin A and SEB (P = .0047) was significantly elevated in the mucus of eight patients with CHSwNP as compared with the nasal mucus of healthy controls. Conclusions: 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.