Respiratory viral infections in otherwise healthy humans with inherited IRF7 deficiency

• DOI: 10.1084/jem.20220202
• Publication Date: 2022-06-07T14:18:13Z
• Authors: Tessa Mollie Camp...; Zhiyong Liu; Qian Zhang; Marcela Moncada-V...; Laura E. Covill; Peng Zhang; Ilad Alavi Darazam; Paul Bastard; Lucy Bizien; Giorgia Bucciol; Sara Lind Enoksson; Emmanuelle Jouanguy; Şemsi Nur Karabela; Taushif Khan; Yasemin Kendir-De...; Andres Augusto Arias; Davood Mansouri; Per Marits; Nico Marr; Isabelle Migeotte; Leen Moens; Tayfun Ozcelik; Isabelle Pellier; Anton Sendel; Sevtap Şenoğlu; Mohammad Shahrooei; C.I. Edvard Smith; Isabelle Vandernoot; Karen Willekens; Kadriye Kart Yaşar; ; Laurent Abel; Alessandro Aiuti; Saleh Al-Muhsen; Fahd Al-Mulla; Mark S. Anderson; Evangelos Andreakos; Andrés A. Arias; Hagit Baris Feldman; Alexandre Belot; Catherine M. Biggs; Dusan Bogunovic; Alexandre Bolze; Anastasiia Bondar...; Ahmed A. Bousfiha; Petter Brodin; Yenan Bryceson; Carlos D. Bustamante; Manish J. Butte; Giorgio Casari; John Christodoulou; Antonio Condino-Neto; Stefan N. Constan...; Megan A. Cooper; Clifton L. Dalgard; Murkesh Desai; Beth A. Drolet; Jamila El Baghdadi; Sara Espinosa-Pad...; Jacques Fellay; Carlos Flores; José Luis Franco; Antoine Froidure; Peter K. Gregersen; Bodo Grimbacher; Filomeen Haerynck; David Hagin; Rabih Halwani; Lennart Hammarström; James R. Heath; Sarah E. Henrickson; Elena W.Y. Hsieh; Eystein Husebye; Kohsuke Imai; Yuval Itan; Erich D. Jarvis; Timokratis Karami...; Kai Kisand; Cheng-Lung Ku; Yu-Lung Lau; Yun Ling; Carrie L. Lucas; Tom Maniatis; Davood Mansouri; László Maródi; Isabelle Meyts; Joshua D. Milner; Kristina Mironska; Trine H. Mogensen; Tomohiro Morio; Lisa F.P. Ng; Luigi D. Notarangelo; Antonio Novelli; Giuseppe Novelli; Cliona O'Farrelly; Satoshi Okada; Keisuke Okamoto; Tayfun Ozcelik; Qiang Pan-Hammars...; Maria Papadaki; Jean W. Pape; Rebeca Perez de D...; David S. Perlin; Graziano Pesole; Anna M. Planas; Carolina Prando; Aurora Pujol; Lluis Quintana-Murci; Sathishkumar Rama...; Laurent Renia; Igor Resnick; Carlos Rodríguez-...; Vanessa Sancho-Sh...; Anna Sediva; Mikko R.J. Seppänen; Mohammed Shahrooei; Anna Shcherbina; Ondrej Slaby; Andrew L. Snow; Pere Soler-Palacín; András N. Spaan; Ivan Tancevski; Stuart G. Tangye; Ahmad Abou Tayoun; Stuart E. Turvey; K M Furkan Uddin; Mohammed J. Uddin; Diederik van de Beek; Donald C. Vinh; Horst von Bernuth; Joost Wauters; Mayana Zatz; Pawel Zawadzki; Helen C. Su; Jean-Laurent Casa...; Peter Bergman; Laurent Abel; Aurélie Cobat; Jean-Laurent Casa...; Isabelle Meyts; Yenan T. Bryceson
• Keywords: Adult; Allergie et immunopathologie; SARS-CoV-2; SARS-Cov-2; viral infections; [SDV]Life Sciences [q-bio]; Brief Definitive Report; 610; COVID-19; Settore MED/03 - GENETICA MEDICA; [SDV] Life Sciences [q-bio]; Virus Diseases; 616; Immunologie; Influenza, Human; Viruses; IRF7; Humans

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.