COVID-19 progression and convalescence in common variable immunodeficiency patients show dysregulated adaptive immune responses and persistent type I interferon and inflammasome activation
Rodríguez-Ubreva, Javier (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Calafell-Segura, Josep (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Calvillo, Celia L. (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Keller, Baerbel (University of Freiburg)
Ciudad, Laura (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Handfield, Louis-François (Wellcome Sanger Institute. Wellcome Genome Campus)
de la Calle-Fabregat, Carlos (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Godoy-Tena, Gerard (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Andrés-León, Eduardo (Instituto de Parasitología y Biomedicina "López-Neyra")
Hoo, Regina (Wellcome Sanger Institute. Wellcome Genome Campus)
Porter, Tarryn (Wellcome Sanger Institute. Wellcome Genome Campus)
Prigmore, Elena (Wellcome Sanger Institute. Wellcome Genome Campus)
Hofmann, Maike (University of Freiburg)
Decker, Annegrit (University of Freiburg)
Martín, Javier (Instituto de Parasitología y Biomedicina "López-Neyra")
Vento Tormo, Roser (Wellcome Sanger Institute. Wellcome Genome Campus)
Warnatz, Klaus (University of Freiburg)
Ballestar, Esteban (East China Normal University (ECNU))
Universitat Autònoma de Barcelona

Fecha:	2024
Resumen:	Common variable immunodeficiency (CVID) is the most prevalent primary immunodeficiency, marked by hypogammaglobulinemia, poor antibody responses, and increased infection susceptibility. The COVID-19 pandemic provided a unique opportunity to study the effects of prolonged viral infections on the immune responses of CVID patients. Here we use single-cell RNA-seq and spectral flow cytometry of peripheral blood samples before, during, and after SARS-CoV-2 infection showing that COVID-19 CVID patients display a persistent type I interferon signature at convalescence across immune compartments. Alterations in adaptive immunity include sustained activation of naïve B cells, increased CD21 B cells, impaired Th1 polarization, CD4 T central memory exhaustion, and increased CD8 T cell cytotoxicity. NK cell differentiation is defective, although cytotoxicity remains intact. Monocytes show persistent activation of inflammasome-related genes. These findings suggest the involvement of intact humoral immunity in regulating these processes and might indicate the need for early intervention to manage viral infections in CVID patients.
Ayudas:	Agencia Estatal de Investigación PID2020-117212RB-I00
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Adaptive Immunity ; Adult ; B-Lymphocytes ; CD8-Positive T-Lymphocytes ; Common Variable Immunodeficiency ; Convalescence ; COVID-19 ; Disease Progression ; Female ; Humans ; Inflammasomes ; Interferon Type I ; Killer Cells, Natural ; Male ; Middle Aged ; SARS-CoV-2 ; Single-Cell Analysis
Publicado en:	Nature communications, Vol. 15 Núm. 1 (december 2024) , p. 10344, ISSN 2041-1723

DOI: 10.1038/s41467-024-54732-x
PMID: 39609471

21 p, 6.3 MB

El registro aparece en las colecciones:
Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Instituto de Investigación contra la Leucemia Josep Carreras
Artículos > Artículos de investigación
Artículos > Artículos publicados