TY - JOUR
T1 - Circulating Proteins Associated with Anti-IL6 Receptor Therapeutic Resistance in the Sera of Patients with Severe COVID-19
AU - Michot, Jean Marie
AU - Dozio, Vito
AU - Rohmer, Julien
AU - Pommeret, Fanny
AU - Roumier, Mathilde
AU - Yu, Haochen
AU - Sklodowki, Kamil
AU - Danlos, François Xavier
AU - Ouali, Kaissa
AU - Kishazi, Edina
AU - Naigeon, Marie
AU - Griscelli, Franck
AU - Gachot, Bertrand
AU - Groh, Matthieu
AU - Bacciarello, Giulia
AU - Stoclin, Annabelle
AU - Willekens, Christophe
AU - Sakkal, Madona
AU - Bayle, Arnaud
AU - Zitvogel, Laurence
AU - Silvin, Aymeric
AU - Soria, Jean Charles
AU - Barlesi, Fabrice
AU - Beeler, Kristina
AU - André, Fabrice
AU - Vasse, Marc
AU - Chaput, Nathalie
AU - Ackermann, Felix
AU - Escher, Claudia
AU - Marabelle, Aurélien
N1 - Publisher Copyright:
© 2024 American Chemical Society.
PY - 2024/11/1
Y1 - 2024/11/1
N2 - 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.
AB - 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.
KW - COVID-19
KW - anti-interleukin 6 receptor therapy
KW - calprotectin
KW - candidate proteins
KW - proteomics
KW - thrombospondin-1
UR - http://www.scopus.com/inward/record.url?scp=85205913495&partnerID=8YFLogxK
U2 - 10.1021/acs.jproteome.2c00422
DO - 10.1021/acs.jproteome.2c00422
M3 - Article
C2 - 39352225
AN - SCOPUS:85205913495
SN - 1535-3893
VL - 23
SP - 5001
EP - 5015
JO - Journal of Proteome Research
JF - Journal of Proteome Research
IS - 11
ER -