B-cell activating factor/Th17/Neutrophils axis plays a role in refractory nasal polyposis

RATIONALE: Immunologic characteristics and pathophysiology of refractory nasal polyposis (NPs) which is intractable to medical treatment after surgery remain unclear. Therefore, we evaluated the immunologic profiles of refractory NPs and investigate their immunologic mechanism of refractoriness.

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.

RESULTS:

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.