Serum Proteomic Profile of Asthmatic Patients after Six Months of Benralizumab and Mepolizumab Treatment
Lorenza Vantaggiato,
Paolo Cameli,
Laura Bergantini,
Miriana d’Alessandro,
Enxhi Shaba,
Alfonso Carleo,
Fabrizio Di Giuseppe,
Stefania Angelucci,
Guido Sebastiani,
Francesco Dotta,
Luca Bini,
Elena Bargagli,
Claudia Landi
Affiliations
Lorenza Vantaggiato
Functional Proteomics Lab, Department of Life Sciences, University of Siena, 53100 Siena, Italy
Paolo Cameli
Complex Operational Unit of Respiratory Diseases and Lung Transplantation, Department Internal and Specialist Medicine, University of Siena, 53100 Siena, Italy
Laura Bergantini
Complex Operational Unit of Respiratory Diseases and Lung Transplantation, Department Internal and Specialist Medicine, University of Siena, 53100 Siena, Italy
Miriana d’Alessandro
Complex Operational Unit of Respiratory Diseases and Lung Transplantation, Department Internal and Specialist Medicine, University of Siena, 53100 Siena, Italy
Enxhi Shaba
Functional Proteomics Lab, Department of Life Sciences, University of Siena, 53100 Siena, Italy
Alfonso Carleo
Department of Pulmonology, Hannover Medical School, 30625 Hannover, Germany
Fabrizio Di Giuseppe
Proteomics Unit, Department of Medical, Oral and Biotechnological Sciences, University “G. d’Annunzio” Chieti-Pescara, 66100 Chieti, Italy
Stefania Angelucci
Proteomics Unit, Department of Medical, Oral and Biotechnological Sciences, University “G. d’Annunzio” Chieti-Pescara, 66100 Chieti, Italy
Guido Sebastiani
Diabetes Unit, Department of Medical Sciences Surgery and Neurosciences, University of Siena, 53100 Siena, Italy
Francesco Dotta
Diabetes Unit, Department of Medical Sciences Surgery and Neurosciences, University of Siena, 53100 Siena, Italy
Luca Bini
Functional Proteomics Lab, Department of Life Sciences, University of Siena, 53100 Siena, Italy
Elena Bargagli
Complex Operational Unit of Respiratory Diseases and Lung Transplantation, Department Internal and Specialist Medicine, University of Siena, 53100 Siena, Italy
Claudia Landi
Functional Proteomics Lab, Department of Life Sciences, University of Siena, 53100 Siena, Italy
Severe eosinophilic asthma is characterized by chronic airway inflammation, oxidative stress, and elevated proinflammatory cytokines, especially IL-5. Mepolizumab and benralizumab are both humanized IgG antibodies directed against IL-5 signaling, directly acting on eosinophils count. Together with the complexity of severe asthma classification and patient selection for the targeted treatment, there is also the urgency to clarify the follow-up of therapy to identify biomarkers, in addition to eosinophils, for the optimal duration of treatment, persistence of effectiveness, and safety. To this purpose, here we performed a follow-up study using differential proteomic analysis on serum samples after 1 and 6 months of both therapies and sera from healthy patients. Statistical analysis by PCA and heatmap analyses were performed, and identified proteins were used for enrichment analysis by MetaCore software. The analysis highlighted 82 differences among all considered conditions. In particular, 30 referred to benralizumab time point (T0, T1B, T6B) and 24 to mepolizumab time point (T0, T1M, T6M) analyses. t-SNE and heatmap analyses evidence that the differential serum protein profile at 6 months of both treatments is more similar to that of the healthy subjects. Among the identified proteins, APOAI, APOC-II, and APOC-III are upregulated principally after 6 months of benralizumab treatment, plasminogen is upregulated after 6 months of both treatments and ceruloplasmin, upregulated already after 1 month of benralizumab, becoming higher after 6 months of mepolizumab. Using enrichment analysis, identified proteins were related to lipid metabolism and transport, blood coagulation, and ECM remodeling.
