TY - JOUR
T1 - Respiratory viral infections in otherwise healthy humans with inherited IRF7 deficiency
AU - COVID Human Genetic Effort
AU - Campbell, Tessa Mollie
AU - Liu, Zhiyong
AU - Zhang, Qian
AU - Moncada-Velez, Marcela
AU - Covill, Laura E
AU - Zhang, Peng
AU - Alavi Darazam, Ilad
AU - Bastard, Paul
AU - Bizien, Lucy
AU - Bucciol, Giorgia
AU - Lind Enoksson, Sara
AU - Jouanguy, Emmanuelle
AU - Karabela, Şemsi Nur
AU - Khan, Taushif
AU - Kendir-Demirkol, Yasemin
AU - Arias, Andres Augusto
AU - Mansouri, Davood
AU - Marits, Per
AU - Marr, Nico
AU - Migeotte, Isabelle
AU - Moens, Leen
AU - Ozcelik, Tayfun
AU - Pellier, Isabelle
AU - Sendel, Anton
AU - Shahrooei, Mohammad
AU - Smith, C I Edvard
AU - Vandernoot, Isabelle
AU - Willekens, Karen
AU - Bergman, Peter
AU - Abel, Laurent
AU - Cobat, Aurélie
AU - Casanova, Jean-Laurent
AU - Meyts, Isabelle
AU - Bryceson, Yenan T
AU - van de Beek, Diederik
N1 - Funding Information:
This work was supported by the Swedish Research Council, Göran Gustafsson Foundation, Karolinska Institute Doctoral Program, Center for Innovative Medicine (CIMED; to Y.T. Bry-ceson), CIMED (to C.I.E. Smith), and CIMED, Stockholm County Council and Karolinska Institute (to P. Bergman). Part of this work was generated within the European Reference Network for rare primary immunodeficiency, autoinflammatory and autoimmune diseases (to C.I.E. Smith and P. Bergman). T.M. Campbell is supported by a Swedish Society for Medical Research postdoctoral grant. The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH; R01AI088364 and R01AI63029), the National Center for Advancing Translational Sciences, NIH Clinical and Translational Science Award program (UL1 TR001866), a Fast Grant from Emergent Ventures, the Mercatus Center at George Mason University, the Yale Center for Mendelian Genomics and the GSP Coordinating Center funded by the National Human Genome Research Institute (UM1HG006504 and U24HG008956), the Yale High-Performance Computing Center (S10OD018521), the Fisher Center for Alzheimer’s Research Foundation, the JPB Foundation, the Meyer Foundation, the French National Research Agency (ANR) under the “Investments for the Future” program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (FRM; EQU201903007798), the ANR GenMISC (ANR-21-COVR-039), the ANRS-COV05, ANR GENVIR (ANR-20-CE93-003) and ANR AABIFNCOV (ANR-20-CO11-0001) projects, the European Union’s Horizon 2020 Research and Innovation Program under grant agreement no. 824110 (EASI-genomics), the Square Foundation, Grandir – Fonds de solidarité pour l’enfance, Fondation du Souffle, the SCOR Corporate Foundation for Science, The French Ministry of Higher Education, Research, and Innovation (MESRI-COVID-19), Institut National de la Santé et de la Recherche Médicale (INSERM), REACTing-INSERM, and the University of Paris. P. Bastard was supported by the MD-PhD program of the Imagine Institute (with the support of the Bettencourt-Schueller Foundation). I. Meyts is a senior clinical investigator at the Research Foundation - Flanders and is supported by the CSL Behring Chair of Primary Immunodeficiencies, a KU Leuven C1 Grant (grant number C16/18/007), a VIB GC PID Grant, the Research Foundation – Flanders (grant numbers G0C8517N, G0B5120N and
Funding Information:
G0E8420N), and the Jeffrey Modell Foundation. I. Migeotte is funded by Fonds Erasme. This work was supported by ERN-RITA.
Publisher Copyright:
© 2022 Campbell et al.
PY - 2022/7/4
Y1 - 2022/7/4
N2 - Autosomal recessive IRF7 deficiency was previously reported in three patients with single critical influenza or COVID-19 pneumonia episodes. The patients' fibroblasts and plasmacytoid dendritic cells produced no detectable type I and III IFNs, except IFN-β. Having discovered four new patients, we describe the genetic, immunological, and clinical features of seven IRF7-deficient patients from six families and five ancestries. Five were homozygous and two were compound heterozygous for IRF7 variants. Patients typically had one episode of pulmonary viral disease. Age at onset was surprisingly broad, from 6 mo to 50 yr (mean age 29 yr). The respiratory viruses implicated included SARS-CoV-2, influenza virus, respiratory syncytial virus, and adenovirus. Serological analyses indicated previous infections with many common viruses. Cellular analyses revealed strong antiviral immunity and expanded populations of influenza- and SARS-CoV-2-specific memory CD4+ and CD8+ T cells. IRF7-deficient individuals are prone to viral infections of the respiratory tract but are otherwise healthy, potentially due to residual IFN-β and compensatory adaptive immunity.
AB - Autosomal recessive IRF7 deficiency was previously reported in three patients with single critical influenza or COVID-19 pneumonia episodes. The patients' fibroblasts and plasmacytoid dendritic cells produced no detectable type I and III IFNs, except IFN-β. Having discovered four new patients, we describe the genetic, immunological, and clinical features of seven IRF7-deficient patients from six families and five ancestries. Five were homozygous and two were compound heterozygous for IRF7 variants. Patients typically had one episode of pulmonary viral disease. Age at onset was surprisingly broad, from 6 mo to 50 yr (mean age 29 yr). The respiratory viruses implicated included SARS-CoV-2, influenza virus, respiratory syncytial virus, and adenovirus. Serological analyses indicated previous infections with many common viruses. Cellular analyses revealed strong antiviral immunity and expanded populations of influenza- and SARS-CoV-2-specific memory CD4+ and CD8+ T cells. IRF7-deficient individuals are prone to viral infections of the respiratory tract but are otherwise healthy, potentially due to residual IFN-β and compensatory adaptive immunity.
UR - https://www.scopus.com/pages/publications/85135444816
U2 - 10.1084/jem.20220202
DO - 10.1084/jem.20220202
M3 - Article
SN - 0022-1007
VL - 219
JO - Journal of experimental medicine
JF - Journal of experimental medicine
IS - 7
M1 - e20220202
ER -