LOX-1-Expressing Immature Neutrophils Identify Critically-Ill COVID-19 Patients at Risk of Thrombotic Complications

Autor: Combadière, Behazine, Adam, Lucille, Guillou, Noëlline, Quentric, Paul, Rosenbaum, Pierre, Dorgham, Karim, Bonduelle, Olivia, Parizot, Christophe, Sauce, Delphine, Mayaux, Julien, Luyt, Charles-Edouard, Boissonnas, Alexandre, Amoura, Zahir, Pourcher, Valérie, Miyara, Makoto, Gorochov, Guy, Guihot, Amélie, Combadière, Christophe
Přispěvatelé: Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Anesthésie réanimation [CHU Pitié-Salpêtrière], Institut E3M [CHU Pitié-Salpêtrière], Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], Gestionnaire, HAL Sorbonne Université 5, Centre d'Immunologie et des Maladies Infectieuses (CIMI), Service d'Immunologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Pneumologie - R3S [CHU Pitié-Salpêtrière] (SPMIR-R3S), Institut de cardiologie [CHU Pitié-Salpêtrière], Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière]
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Frontiers in Immunology
Frontiers in Immunology, Frontiers, 2021, 12, ⟨10.3389/fimmu.2021.752612⟩
Frontiers in Immunology, 2021, 12, pp.752612. ⟨10.3389/fimmu.2021.752612⟩
ISSN: 1664-3224
Popis: International audience; Background: Lymphopenia and the neutrophil/lymphocyte ratio may have prognostic value in COVID-19 severity.Objective: We investigated neutrophil subsets and functions in blood and bronchoalveolar lavage (BAL) of COVID-19 patients on the basis of patients’ clinical characteristics.Methods: We used a multiparametric cytometry profiling based to mature and immature neutrophil markers in 146 critical or severe COVID-19 patients.Results: The Discovery study (38 patients, first pandemic wave) showed that 80% of Intensive Care Unit (ICU) patients develop strong myelemia with CD10−CD64+ immature neutrophils (ImNs). Cellular profiling revealed three distinct neutrophil subsets expressing either the lectin‐like oxidized low‐density lipoprotein receptor‐1 (LOX‐1), the interleukin-3 receptor alpha (CD123), or programmed death-ligand 1 (PD-L1) overrepresented in ICU patients compared to non-ICU patients. The proportion of LOX-1- or CD123-expressing ImNs is positively correlated with clinical severity, cytokine storm (IL-1β, IL-6, IL-8, TNFα), acute respiratory distress syndrome (ARDS), and thrombosis. BALs of patients with ARDS were highly enriched in LOX-1-expressing ImN subsets and in antimicrobial neutrophil factors. A validation study (118 patients, second pandemic wave) confirmed and strengthened the association of the proportion of ImN subsets with disease severity, invasive ventilation, and death. Only high proportions of LOX-1-expressing ImNs remained strongly associated with a high risk of severe thrombosis independently of the plasma antimicrobial neutrophil factors, suggesting an independent association of ImN markers with their functions.Conclusion: LOX-1-expressing ImNs may help identifying COVID-19 patients at high risk of severity and thrombosis complications.
Databáze: OpenAIRE
Externí odkaz: