Immune modulatory effects of novel monoclonal antibodies target therapies in severe eosinophilic asthma patients

New anti IL-5 antibodies, mepolizumab and benralizumab, have recently been approved for severe asthma, sharing the same inclusion criteria. To contribute on biomarkers research leading to the personalized choice, we investigated L-selectin, KL-6 and lymphocyte subsets as bioindicators of airways hyper-responsiveness and remodelling and to phenotype patients according to their answer to the treatment. L‐selectin mediates leukocyte rolling of lung endothelium and its expression on T cells is increased in asthma patients. Regulatory T cells (Tregs) suppress inflammation by secreting a wide variety of cytokines that inhibit T cell proliferation. A cohort of 28 patients affected by severe eosinophilic asthma were treated with anti IL-5 drugs: 20 with Mepolizumab and 8 with Benralizumab. Lymphocytes subsets, Regulatory T cells and CD4+CD62L+ cells were analyzed through flow cytometry, Serum L-selectin quantification was performed by bead-based multiplex analysis, while KL-6 was analyzed through CLEIA. Clinical, functional and immunological data at baseline (T0), after one month (T1) and 6 months of therapy were collected in a database. All treated patients showed variations in FEV1, FEV1/FVC ratio and peripheral eosinophils for both drugs. Mepolizumab treated patients also showed significant differences between T0 and T1 in CD8+ and NK-T like cells percentages and a significant increase in L-selectin concentrations. Stratifying the cohort of our patients in “early responders and partial responders at T0 they showed significant differences in peripheral eosinophils, sL-selectin, and KL-6, while no differences were found at T0 between “early responders” and “partial responders” patients treated with Benralizumab. In a subgroup of 14 mepolizumab treated patients, immunological data showed an increase in Tregs and CD4+CD62L+ at T1. Soluble L-selectin concentrations were lower at T1. CD45+ and CD62L+ cell features differed significantly in early and partial responders before and after therapy. The FEV1/FVC ratio showed an indirect correlation with L-selectin levels (r=-0.6, p=0.03), peripheral eosinophilia (r=-0.7, p=0.01). This real-life study provides new insights for the personalized approach to severe asthma therapy. Although preliminary, the results indicate that besides to peripheral eosinophils, other molecules are useful as biomarkers of early response that can also involving in the pathogenesis of severe asthma. Mepolizumab therapy was found to modulate immune response, restoring immune balance in patients with SEA. L-selectin and Tregs were also proposed as biomarkers of response to mepolizumab treatment.