The impact of anti-IL5 therapies on patients with severe eosinophilic asthma: a proteomic approach

BACKGROUND: Mepolizumab and benralizumab are humanized IgG antibodies directed against IL-5 signaling, acting on eosinophils count and activity, approved for the treatment of severe eosinophilic asthma (SEA). Aside clinical efficacy, little is known about their biomolecular and metabolic effects. AIM: to investigate and compare the serum proteomic profiles variations of SEA patients treated with anti-IL5 drugs METHODS: we prospectively performed differential proteomic analysis on serum samples of healthy controls (HC) and SEA patients at baseline (T0), after 1 month (T1) and 6 months (T6) of treatment with mepolizumab and benralizumab. Statistical analysis by PCA and heatmap analyses were performed and identified proteins were used for enrichment analysis by MetaCore software. RESULTS: At T6, we observed that serum protein profile of both SEA subgroups was similar to that of HC. Identified proteins were mainly related to lipid metabolism and transport, blood coagulation and antioxidant processes. APOAI, APOC-II and APOC-III were up-regulated only in benralizumab patients, while plasminogen and ceruloplasmin were up-regulated at T6 of both treatment subgroups. CONCLUSIONS: mepolizumab and benralizumab were able to remodulate serum protein profile of SEA patients, which appeared similar to HC after 6 months of therapy. Our results suggest that biomolecular effects of anti-IL5 drugs goes beyond eosinophils9 depletion.