Eosinophilic airway
inflammation, complicated by
bronchial asthma and eosinophilic chronic
rhinosinusitis (ECRS), is difficult to treat. The disease may become refractory when eosinophilic
mucin associated with
eosinophil peroxidase (EPX) and
autoantibodies fills in the paranasal sinus and small airway. This study investigated the functional role of an anti-EPX antibody in eosinophilic
mucin of ECRS in eosinophilic airway
inflammation. Eosinophilic
mucin was obtained from patients with ECRS. The effects of the anti-EPX antibody on dsDNA release from eosinophils and eosinophilic
mucin decomposition were evaluated. Immunofluorescence or
enzyme-linked
immunosorbent assays were performed to detect the anti-EPX antibody and its supernatant and serum levels in eosinophilic
mucin, respectively. The serum levels of the anti-EPX antibody were positively correlated with sinus computed tomography score and fractionated exhaled
nitrogen oxide. Patients with refractory ECRS had higher serum levels of the anti-EPX antibody than those without. However,
dupilumab treatment decreased the serum levels of the anti-EPX antibody.
Immunoglobulins (Igs) in the immunoprecipitate of
mucin supernatants enhanced dsDNA release from eosinophils, whereas the neutralization of Igs against EPX stopped dsDNA release. Furthermore, EPX antibody neutralization accelerated
mucin decomposition and restored
corticosteroid sensitivity. Taken together, the anti-EPX antibody may be involved in the formulation of eosinophilic
mucin and be used as a
clinical marker and therapeutic target for intractable eosinophilic airway
inflammation.