Mepolizumab and Benralizumab in Severe Eosinophilic Asthma: Preliminary Results of a Proteomic Study
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ASTHMA
Mepolizumab and Benralizumab in Severe Eosinophilic Asthma: Preliminary Results of a Proteomic Study Lorenza Vantaggiato1 · Marco Perruzza2 · Rosa Metella Refini2 · Laura Bergantini2 · Miriana d’Alessandro2 · Paolo Cameli2 · Davide Perruzza3 · Luca Bini1 · Elena Bargagli2 · Claudia Landi1,2 Received: 27 April 2020 / Accepted: 7 July 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Benralizumab and mepolizumab are new therapies for severe eosinophilic asthma. Theyare both humanized IgG antibodies, targeting the IL‐5 receptor and IL‐5, respectively, suppressing the corresponding pathways. No specific biomarkers have been proposed to evaluate treatment response to benralizumab or mepolizumab. The aim of this proteomic study was to compare serum protein profiles of patients with severe eosinophilic asthma before and after anti‐IL5 or anti‐IL5R therapies. Proteomic analysis highlighted 22 differently abundant spots. Among the proteins identified, CAYP1, A1AT and A2M expression was significantly modified in both groups of patients after therapies while ceruloplasmin showed a significant modification in the group of benralizumab treatment. These differentially expressed proteins could be potential biomarkers of response to mepolizumab and benralizumab treatments and need further evaluation. Keywords Mepolizumab · Benralizumab · Proteomic · Serum · Severe eosinophilic asthma
Background Mepolizumab is a humanized monoclonal N‐glycosylated IgG1/k antibody that binds the IL-5α-chain, preventing it from associating with the α subunit of the IL-5 receptor [1]. Benralizumab targets the IL-5Ra subunit expressed by eosinophils and basophils and has high affinity for human FcγRIIIa, resulting in enhanced ADCC action [2] and a consequent reduction in circulating levels of eosinophils Lorenza Vantaggiato and Marco Perruzza should be regarded as joint first authors. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00408-020-00379-6) contains supplementary material, which is available to authorized users. * Claudia Landi [email protected]; [email protected] 1
Functional Proteomics Lab, Department of Life Sciences, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy
2
UOC Respiratory Diseases and Lung Transplantation, Department Internal and Specialist Medicine, University of Siena, Siena, Italy
3
Unit of Basic and Applied Biosciences, University of Teramo, Via Balzarini 1, 64100 Teramo, Italy
and basophils [3]. Mepolizumab [4] and benralizumab [5] have been demonstrated to produce a significant reduction in asthma exacerbations, steroid requirements and eosinophil count, with significant improvement in lung function parameters and clinical symptoms. These new drugs need further study, especially concerning the optimal duration of treatment, persistence of effect, response biomarkers and candidate selection. The aim of this preliminary study was to compare the serum proteomic profiles of patients with severe asthma b
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