METHODS: Revision ESS subjects (N=86) requiring revision surgery due to failed medical treatment after surgeries, primary ESS subjects (N=20) and controls (N=7) were enrolled. We investigated 21 inflammatory markers and autoimmunity markers and compared their values in each group. To confirm the role of BAFF, an anti-BAFF neutralizing antibody was administered in the ovalbumin-staphylococcal enterotoxin B-induced murine NPs model.
Neutrophilic infiltration, MPO, IL-8, and Th17-associated cytokines were upregulated in revision NPs compared with control and primary NPs. These immunologic characteristics were demonstrated in both eosinophilic and non-eosinophilic revision NPs, but more prominent in non-eosinophilic NPs. Eosinophils-associated markers (ECP, CCL11, and CCL24) was upregulated in both primary and revision NPs. However, there was no difference between two subtypes. BAFF and anti-ds-DNA Ab were also enhanced in revision NPs than primary ones, which were more remarkable in non-eosinophilic NPs. BAFF expression was well correlated to Th17/Th1 cytokines such as IL-17A, IL-23, and IFN-γ in NPs. To confirm whether BAFF/Th17/Neutrophil axis is active in nasal inflammation, anti-BAFF was administrated in animal model. After BAFF blockade, the expression of CXCL1, IL23p19, IL6, anti-ds-DNA IgG and neutrophilic infiltration were effectively were inhibited.
CONCLUSIONS: Our results suggest refractory NPs showed upregulation of BAFF, Th17/Th1 cytokines and neutrophils, compared with primary cases. Active BAFF/Th17/neutrophil axis may play a significant role in refractoriness.