Role of CD39 in COVID-19 Severity: Dysregulation of Purinergic Signaling and Thromboinflammation

Frontiers in Immunology

Immunology

Jordi Solé-Violán¹  Carlos Rodríguez-Gallego²  Kapil Nanwani-Nanwani³  José Juan Ruíz-Hernández⁴  Ana Van-Den-Rym⁵  Rebeca Pérez-de-Diego⁵  Alberto Mangas⁶  Sara García-Tovar⁶  Enrique Alfaro⁶  Ester Zamarrón⁷  Elena Díaz-García⁷  Carolina Cubillos-Zapata⁷  Raúl Galera⁷  Francisco García-Rio⁸  Eduardo López-Collazo⁹ 

[1] Biomedical Research Networking Center on Respiratory Diseases (CIBERES), Madrid, Spain;Intensitive Care Medicine, Gran Canaria Dr Negrín University Hospital, Gran Canaria, Spain;Departament of Immunology, Gran Canaria Dr Negrín University Hospital, Gran Canaria, Spain;Department of Clinical Sciences, University Fernando Pessoa Canarias, Las Palmas de Gran Canaria, Spain;Department of Intensive Medicine, La Paz University Hospital, Madrid, Spain;Department of Internal Medicine, Gran Canaria Dr Negrín University Hospital, Gran Canaria, Spain;Laboratory of Immunogenetics of Human Diseases, La Paz University Hospital, Instituto de Investigación Biomédica del Hospital Universitario la Paz (IdiPAZ), Madrid, Spain;Interdepartmental Group of Immunodeficiencies, Madrid, Spain;Respiratory Diseases Group, Respiratory Service, La Paz University Hospital, Instituto de Investigación Biomédica del Hospital Universitario la Paz (IdiPAZ), Madrid, Spain;Respiratory Diseases Group, Respiratory Service, La Paz University Hospital, Instituto de Investigación Biomédica del Hospital Universitario la Paz (IdiPAZ), Madrid, Spain;Biomedical Research Networking Center on Respiratory Diseases (CIBERES), Madrid, Spain;Respiratory Diseases Group, Respiratory Service, La Paz University Hospital, Instituto de Investigación Biomédica del Hospital Universitario la Paz (IdiPAZ), Madrid, Spain;Biomedical Research Networking Center on Respiratory Diseases (CIBERES), Madrid, Spain;Faculty of Medicine, Autonomous University of Madrid, Madrid, Spain;The Innate Immune Response Group, La Paz University Hospital, Instituto de Investigación Biomédica del Hospital Universitario la Paz (IdiPAZ), Madrid, Spain;

关键词: COVID-19;    thromboinflammation;    CD39;    purinergic dysregulation;    hypoxia;   

DOI  :  10.3389/fimmu.2022.847894

 received in 2022-01-03, accepted in 2022-01-13,  发布年份 2022

来源: Frontiers

【 摘 要 】

CD39/NTPDase1 has emerged as an important molecule that contributes to maintain inflammatory and coagulatory homeostasis. Various studies have hypothesized the possible role of CD39 in COVID-19 pathophysiology since no confirmatory data shed light in this regard. Therefore, we aimed to quantify CD39 expression on COVID-19 patients exploring its association with severity clinical parameters and ICU admission, while unraveling the role of purinergic signaling on thromboinflammation in COVID-19 patients. We selected a prospective cohort of patients hospitalized due to severe COVID-19 pneumonia (n=75), a historical cohort of Influenza A pneumonia patients (n=18) and sex/age-matched healthy controls (n=30). CD39 was overexpressed in COVID-19 patients’ plasma and immune cell subsets and related to hypoxemia. Plasma soluble form of CD39 (sCD39) was related to length of hospital stay and independently associated with intensive care unit admission (adjusted odds ratio 1.04, 95%CI 1.0-1.08, p=0.038), with a net reclassification index of 0.229 (0.118-0.287; p=0.036). COVID-19 patients showed extracellular accumulation of adenosine nucleotides (ATP and ADP), resulting in systemic inflammation and pro-coagulant state, as a consequence of purinergic pathway dysregulation. Interestingly, we found that COVID-19 plasma caused platelet activation, which was successfully blocked by the P2Y12 receptor inhibitor, ticagrelor. Therefore, sCD39 is suggested as a promising biomarker for COVID-19 severity. As a conclusion, our study indicates that CD39 overexpression in COVID-19 patients could be indicating purinergic signaling dysregulation, which might be at the basis of COVID-19 thromboinflammation disorder.

【 授权许可】

Unknown   
Copyright © 2022 Díaz-García, García-Tovar, Alfaro, Zamarrón, Mangas, Galera, Ruíz-Hernández, Solé-Violán, Rodríguez-Gallego, Van-Den-Rym, Pérez-de-Diego, Nanwani-Nanwani, López-Collazo, García-Rio and Cubillos-Zapata