Staphylococcus aureus enterotoxins 1 Staphylococcus aureus-derived superantigens in nasal polyp disease 1 2 Peter Tomassen, M.D. 3 Thibaut Van Zele, M.D., Ph.D. 4 Philippe Gevaert, M.D., Ph.D. 5 Nan Zhang, M.D., Ph.D. 6 Claudina Perez-Novo, Ph.D. 7 Nicholas Van Bruaene, M.D. 8 Joke Patou, M.D. 9 Claus Bachert, M.D., Ph.D. 10 11 Upper Airway Research Laboratory (URL) 12 Department of Otorhinolaryngology 13 Ghent University 14 De Pintelaan 185 15 9000 Gent, Belgium 16 peter.tomassen@ugent.be 17 18 19 Abbreviations used 20 AERD aspirin-exacerbated respiratory disease 21 ASNP aspirin sensitive nasal polyps 22 ATNP aspirin tolerant nasal polyps 23 CRSsNP chronic rhinosinusitis without nasal polyps 24 CRSwNP chronic rhinosinusitis with nasal polyps 25 CysLT cysteinyl leukotrienes 26 ECP eosinophil cationic protein 27 IFN-γ interferon-gamma 28 IL interleukin 29 MHC major histocompatibility complex 30 NP nasal polyps 31 SA Staphylococcus aureus 32 SAE-IgE IgE antibodies to SAE 33 SAE Staphylococcus aureus enterotoxin-like toxins 34 SEA - SEU Staphylococcal enterotoxin A - U 35 TCR T cell receptor 36 TGF-β transforming growth factor beta 37 Th T helper 38 TNF-α tumor necrosis factor alpha 39 TSST-1 toxic shock syndrome toxin-1 40 41 Core messages 42 • Staphylococcus aureus secretes enterotoxins, which can cause an intense polyclonal stimulation of the 43 adaptive immune system and drive it towards a T helper 2 response. 44 • This superantigen mechanism is involved in the pathogenesis of nasal polyps in at least 50% of the 45 cases. 46 • The superantigenic effect is hallmarked by immunoglobulin changes in biopsies: high total IgE, 47 polyclonal IgE to multiple allergens, and IgE specific to S. aureus enterotoxins. Serum 48 immunoglobulins only partially coincide with biopsy findings. 49 • Patients with this local IgE pattern have an increased risk of asthma and aspirin-exacerbated 50 respiratory disease. 51 • Future treatment with topical or systemic antibiotics, and monoclonal antibodies to IgE and interleukin 52 5 are under investigation. 53 54 55