Serum Amphiregulin expression in severe asthma patients treated with anti-IL-5 therapy

Rationale: The purpose of the study is to investigate the hypothesis that anti-IL-5 humanized monoclonal antibody Mepolizumab (MEP) could have a role in both eosinophils and pro-fibrotic mechanisms. Methods: The study involved 19 severe asthmatic patients (age range 43-68, 10 females), who received MEP for at least 1 year. Clinical and functional parameters (FEV1%, FVC%, FeNO levels, blood eosinophils, Asthma Control Test (ACT), Oral Corticosteroid (OCS) administration, exacerbations) and serum the levels of Amphiregulin were evaluated at baseline and after treatment. Results: After treatment, the blood eosinophil count decreased from 750 ± 470,2 eos/μL to 98,53 ± 53,21 eos/μL (p < 0.05). ACT score improved from 18,1±5,0 to 22,8±3,4 (p<0.05). Exacerbation rate decreased from 3.3± 2.5 per year to 0.8± 1,9/year (p < 0.05). The daily dose of 12.4 ± 7,8 mg prednisone decreased to 2.1 ± 6.3 mg/day (p < 0.5). FeNO level decreased from 75,3± 57,7 ppb to 53,8± 41,5 ppb after 12 months. The FEV1% predicted increased significantly (73,1± 24 vs 81,3±18,2), whereas the FVC% predicted showed no significant change. Serum Amphiregulin levels decreased significantly from 15,11± 5,78 pg/mL at baseline to 11,49±3,69 pg/mL after treatment (<0.05). Conclusions: Our findings support the hypothesis that MEP is able to reduce tissue inflammation and remodelling by acting on both eosinophils and Th2 pathway, as well as on amphiregulin production. In particular, the down-regulation of amphiregulin may result in a weakening of the pro-fibrotic process and in a reduced triggering on eosinophils.