ORIGINAL ARTICLE EXPERIMENTAL ALLERGY AND IMMUNOLOGY Mucosal tissue polyclonal IgE is functional in response to allergen and SEB N. Zhang 1,2 *, G. Holtappels 1 *, P. Gevaert 1 , J. Patou 1 , B. Dhaliwal 3 , H. Gould 3 & C. Bachert 1 1 Department of Oto-Rhino-Laryngology, Upper Airway Research Laboratory (URL), Ghent University Hospital, Ghent, Belgium; 2 Department of Oto-Rhino-Laryngology, Zhongshan City Peoples Hospital, Zhongshan, Guangdong Province, China; 3 Randall Division of Cell and Molecular Biophysics, New Hunt’s House, King’s College London, Guy’s Campus, London, UK To cite this article: Zhang N, Holtappels G, Gevaert P, Patou J, Dhaliwal B, Gould H, Bachert C. Mucosal tissue polyclonal IgE is functional in response to allergen and SEB. Allergy 2011; 66: 141–148. Evidence is accumulating that Staphylococcus aureus (SA) plays an important role as disease modifiers in upper and lower airway disease, esp. nasal polyps (NP) and asthma, by releasing enterotoxins (Staphylococcus aureus enterotoxins (SAEs)) (1–5). Staphylococcus aureus enterotoxins have been shown to polyclonally activate T-cells, releasing preferentially Th2 cytokines (6) and amplifying eosinophilic inflammation, and B-cells to induce polyclonal IgE and IgG/IgG4 produc- tion (7). The presence of SAE-IgE antibodies (abs) in the tis- sue is associated with high total IgE and eosinophil cationic protein (ECP) values; high IgE titers of up to 5000 kU/l can be found in SAE-IgE+ polyp tissue, as demonstrated earlier (1). Apart from an effect on T- and B-cells, other impact of SAEs on the local inflammation has been shown, such as the inhibition of T regulatory cells (8), the reduction of eosino- phil apoptosis (9) and the induction of chemokines from epithelial cells (10). We recently could demonstrate that the impact of SAEs on the local immune reaction in NP tissue increases the risk of co-morbid asthma (11). Indirect evidence from the comparison of IgE levels in serum and Keywords IgE; mast cells; nasal polyps; polyclonal; superantigens. Correspondence Nan Zhang, MD, PhD, Upper Airway Research Laboratory (URL), Department of Oto-Rhino-Laryngology, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium. Tel.: 0032 9240 6423 Fax: 0032 9240 4993 E-mail: nan.zhang@ugent.be *These authors contributed equally to this work. Accepted for publication 16 June 2010 DOI:10.1111/j.1398-9995.2010.02448.x Edited by: Hans-Uwe Simon Abstract Background: Staphylococcus aureus may modify airway disease by inducing local formation of polyclonal IgE antibodies (abs), the role of which is unknown. Methods: Nasal mucosal tissue and serum was obtained from 12 allergic rhinitis (AR) and 14 nasal polyp (NP) subjects. Skin prick tests were performed, and total and specific IgE abs to inhalant allergens and enterotoxin B were determined in serum and tissue. Tissue fragments were stimulated with anti-IgE, enterotoxin B, or grass and house dust mite allergens in different concentrations for 30 min. RBL SX38 cells were sensitized with NP homogenates containing IgE and stimulated with grass pollen extracts. Results: In AR patients, degranulation of tissue mast cells upon allergen exposure and presence of specific IgE to inhalant allergens corresponded in almost all cases. Total IgE concentrations in serum and mucosal tissue homogenates highly corre- lated. In contrast, in NP patients, reactivity of tissue mast cells upon allergen expo- sure and presence of specific IgE to inhalant allergens or Staphylococcus aureus enterotoxin B corresponded for tissue, but not for serum. Total IgE was signifi- cantly higher in tissue compared to serum and failed to show correlation. Tissue IgE to grass pollen was functional to degranulate RBL cells. Conclusion: We here demonstrate that mucosal IgE abs in NP tissue are functional and able to activate mast cells; specific IgE abs in NP tissue can be found indepen- dently of their presence in serum. We postulate that superantigen-induced poly- clonal IgE in airway disease contributes to chronic inflammation by continuously activating mast cells. Abbreviations abs, antibodies; AR, allergic rhinitis; GP, grass pollen allergens; HDM, house dust mite allergens; IT, inferior turbinate; NIP, 4-hydroxy-3-iodo-5-nitrophenylacetate; NP, nasal polyps; PGD2, prostaglandin D2; SA, Staphylococcus aureus; SAE, Staphylococcus aureus enterotoxins; SEB, Staphylococcus aureus enterotoxin B; SPT, skin prick test; TCM, tissue culture medium. Allergy Allergy 66 (2011) 141–148 ª 2010 John Wiley & Sons A/S 141