European view on the immunopathology of nasal polyposis: first results of the GA²LEN sinusitis cohort study

Introduction and aim: Chronic rhinosinusitis with nasal polyposis is in Caucasians hallmarked by a Th-2-linked eosinophilic inflammation with polyclonal IgE production. Although evidence for a disease-modifying role of IgE specific to Staphylococcal enterotoxins (SAE-IgE) is well established, there have been variable reports on their prevalence in nasal polyp patients. We aimed to characterize the epidemiology of SAE-IgE-positivity and its impact on inflammation in a large pan-European population of chronic rhinosinusitis (CRS) subjects. Material and methods: The study was designed as a multicenter, non-matched case-control study, and recruited CRS subjects with nasal polyps (CRSwNP), without nasal polyps (CRSsNP), and controls undergoing septoplasty or conchotomy. Surgery was conducted independently from the study. Serum, nasal secretions and tissue were analyzed for a set of cytokines and for SAE-IgE (SEA, SEC and TSST-1). Results: 848 subjects were enrolled, of which 301 were operated. Of these, 90 were controls, 96 had CRSsNP, and 105 had CRSwNP. SAE-IgE was detectable in tissue homogenates of 23,5 % of CRSwNP subjects, with considerable geographic variation. They were not detected in controls or in CRSsNP. SAE-IgE positive CRSwNP patients had an increased prevalence of asthma but not of atopy or smoking history. Concentrations of ECP, total IgE, IL-5, IL-1-beta, IL-6, IL-8, but not of TNF-alpha, MPO, IFN-gamma, IL-17 or TGF-beta-1, were significantly increased in tissue homogenates of SAE-IgE positive nasal polyps compared to SAE-IgE negative nasal polyps. In nasal secretions, increases in total IgE, sCD23, sIL-5R-alpha, IL-6 and IL-17 were significant. In serum, ECP, and total IgE were increased significantly. Conclusions: In a large European population, SAE-IgE is detected in CRSwNP to a variable extent, indicating environmental and genetic predisposition to superantigen mediated disease. SAE-IgE is associated with an intense Th2-linked, IL-5 driven eosinophilic inflammation with high IgE production, confirming previous evidence. A systemic effect linking CRSwNP with asthma is suggested