Circulating Proteins Associated with Anti-IL6 Receptor Therapeutic Resistance in the Sera of Patients with Severe COVID-19

Jean Marie Michot, Vito Dozio, Julien Rohmer, Fanny Pommeret, Mathilde Roumier, Haochen Yu, Kamil Sklodowki, François Xavier Danlos, Kaissa Ouali, Edina Kishazi, Marie Naigeon, Franck Griscelli, Bertrand Gachot, Matthieu Groh, Giulia Bacciarello, Annabelle Stoclin, Christophe Willekens, Madona Sakkal, Arnaud Bayle, Laurence ZitvogelAymeric Silvin, Jean Charles Soria, Fabrice Barlesi, Kristina Beeler, Fabrice André, Marc Vasse, Nathalie Chaput, Felix Ackermann, Claudia Escher, Aurélien Marabelle

    Résultats de recherche: Contribution à un journalArticleRevue par des pairs

    Résumé

    Circulating proteomes provide a snapshot of the physiological state of a human organism responding to pathogenic challenges and drug interventions. The outcomes of patients with COVID-19 and acute respiratory distress syndrome triggered by the SARS-CoV2 virus remain uncertain. Tocilizumab is an anti-interleukin-6 treatment that exerts encouraging clinical activity by controlling the cytokine storm and improving respiratory distress in patients with COVID-19. We investigate the biological determinants of therapeutic outcomes after tocilizumab treatment. Overall, 28 patients hospitalized due to severe COVID-19 who were treated with tocilizumab intravenously were included in this study. Sera were collected before and after tocilizumab, and the patient’s outcome was evaluated until day 30 post-tocilizumab infusion for favorable therapeutic response to tocilizumab and mortality. Hyperreaction monitoring measurements by liquid chromatography-mass spectrometry-based proteomic analysis with data-independent acquisition quantified 510 proteins and 7019 peptides in the serum of patients. Alterations in the serum proteome reflect COVID-19 outcomes in patients treated with tocilizumab. Our results suggested that circulating proteins associated with the most significant prognostic impact belonged to the complement system, platelet degranulation, acute-phase proteins, and the Fc-epsilon receptor signaling pathway. Among these, upregulation of the complement system by activation of the classical pathway was associated with poor response to tocilizumab, and upregulation of Fc-epsilon receptor signaling was associated with lower mortality.

    langue originaleAnglais
    Pages (de - à)5001-5015
    Nombre de pages15
    journalJournal of Proteome Research
    Volume23
    Numéro de publication11
    Les DOIs
    étatPublié - 1 nov. 2024

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