Fungal-specific humoral response in eosinophilic mucus chronic rhinosinusitis

Objectives/Hypothesis: An immunoglobulin (Ig)E-mediated allergic pathogenesis is presumed in allergic fungal sinusitis (AFS), yet extensive polyps and eosinophilic mucus (EM) in the paranasal sinuses may also occur in the absence of allergy. Although a noninvasive fungal pathogenesis is presumed in all chronic rhinosinusitis with EM (EMCRS), fungal-specific nonallergic immune responses have not been thoroughly investigated. We tested the hypothesis that there is a fungal-specific humoral response in EMCRS and that it is not confined to IgE. Study Design: EMCRS patients were prospectively stratified into subgroups based on the presence or absence of fungi within EM and of fungal-specific systemic IgE. There were 12 AFS, 5 AFS-like, 8 nonallergic fungal eosinophilic sinusitis (NAFES), and 5 nonallergic, nonfungal eosinophilic sinusitis (NANFES) patients. Methods: Alternaria alternata and Aspergillus fumigatus-specific serum IgE, IgG, IgM, and IgA was measured by enzyme-linked immunosorbent assay and compared with strictly defined healthy and disease-control groups. Results: Fungal-specific IgG (Alternaria alternata P = .0002; Aspergillus fumigatus P = .004), and IgA levels (Alternaria alternata P = .0016; Aspergillus fumigatus P = .002) were higher in EMCRS compared with healthy volunteers but not with disease controls. Fungal-specific IgG3 levels were significantly elevated in all the EMCRS subgroups compared with controls for either fungal antigen (P < .0001). Importantly, fungal-specific IgE levels were not significantly different between fungal-allergic EMCRS and disease controls. Conclusions: Fungal-specific immunity characterized by serum IgG3 and not IgE, distinguished the EMCRS subgroups from control groups regardless of the presence of fungus within EM or of systemic fungal allergy. Fungal-specific IgE responses in fungal-allergic EMCRS were no different to those in fungal-allergic controls, thus challenging the presumption of a unique pathogenic role of fungal allergy in "allergic fungal sinusitis.".