A sensitive assay for measuring whole- blood responses to type I IFNs

• 成果类型: Article
• 署名作者: Gervais, Adrian; Le Floc'h, Corentin; Le Voyer, Tom; Bizien, Lucy; Bohlen, Jonathan; Celmeli, Fatih; Al Qureshah, Fahd; Masson, Cecile; Rosein, Jeremi; Chbihi, Marwa; Levy, Romain; Castagnoli, Riccardo; Rothenbuhler, Anya; Jouanguy, Emmanuelle; Zhang, Qian; Zhang, Shen - Ying; Beziat, Vivien; Bustamante, Jacinta; Puela, Anne; Bastard, Paul; Casanova, Jean- Laurent
• 署名单位: Institut National de la Sante et de la Recherche Medicale (Inserm); Assistance Publique Hopitaux Paris (APHP); Universite Paris Cite; Hopital Universitaire Necker-Enfants Malades - APHP; Universite Paris Cite; Institut National de la Sante et de la Recherche Medicale (Inserm); Rockefeller University; Assistance Publique Hopitaux Paris (APHP); Universite Paris Cite; Hopital Universitaire Saint-Louis - APHP; Universite Paris Cite; Institut National de la Sante et de la Recherche Medicale (Inserm); Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Assistance Publique Hopitaux Paris (APHP); Universite Paris Cite; Hopital Universitaire Necker-Enfants Malades - APHP; Assistance Publique Hopitaux Paris (APHP); Universite Paris Cite; Hopital Universitaire Necker-Enfants Malades - APHP; University of Pavia; Assistance Publique Hopitaux Paris (APHP); Hopital Universitaire Bicetre - APHP; Howard Hughes Medical Institute; Assistance Publique Hopitaux Paris (APHP); Universite Paris Cite; Hopital Universitaire Necker-Enfants Malades - APHP
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-12778
• DOI: 10.1073/pnas.2402983121
• 发表日期: 2024-10-01
• 关键词: nf-kappa-b; interferon-alpha; neutralizing antibodies; inducible protein-10; covid-19 patients; autoantibodies; patient; disease; infections; mutations

摘要

Human inborn errors of the type I IFN response pathway and auto-Abs neutralizing IFN-alpha,-beta, and/or-omega can underlie severe viral illnesses. We report a simple assay for the detection of both types of condition. We stimulate whole blood from healthy individuals and patients with either inborn errors of type I IFN immunity or auto-Abs against type I IFNs with glycosylated human IFN-alpha 2,-beta, or-omega. As controls, we add a monoclonal antibody (mAb) blocking the type I IFN receptors and stimulate blood with IFN-gamma (type II IFN). Of the molecules we test, IP-10 (encoded by the interferon- stimulated gene (ISG) CXCL10) is the molecule most strongly induced by type I and type II IFNs in the whole blood of healthy donors in an ELISA-like assay. In patients with inherited IFNAR1, IFNAR2, TYK2, or IRF9 deficiency, IP-10 is induced only by IFN-gamma, whereas, in those with auto-Abs neutralizing specific type I IFNs, IP-10 is also induced by the type I IFNs not neutralized by the auto-Abs. The measurement of type I and type II IFN- dependent IP-10 induction therefore constitutes a simple procedure for detecting rare inborn errors of the type I IFN response pathway and more common auto-Abs neutralizing type I IFNs.