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

Human inborn errors of the type I IFN response pathway and auto-Abs neutralizing IFN-α, -β, and/or -ω 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-α2, -β, or -ω. As controls, we add a monoclonal antibody (mAb) blocking the type I IFN receptors and stimulated blood with IFN-γ (type II IFN). Of the molecules we test, IP-10 (encoded by the interferon-stimulated gene (ISG) <i>CXCL10</i>) 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-γ, 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.

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Publication Details

Journal
Proceedings of the National Academy of Sciences
Published
2024-09-23
DOI
https://doi.org/10.1073/pnas.2402983121
Citations
15
Primary Topic
interferon and immune responses
Type
article
Field-Weighted Citation Impact
3.61

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article

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

Paul Bastard, Fahd Al Qureshah, Qian Zhang, Jean‐Laurent Casanova et al.
15 citations
Proceedings of the National Academy of Sciences
interferon and immune responses
3.61
article

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

Paul Bastard, Fahd Al Qureshah, Qian Zhang, Jean‐Laurent Casanova, Riccardo Castagnoli, Corentin Le Floc’h, Lucy Bizien, Cécile Masson, Jérémie Rosain, Romain Lévy, Anne Puel, Fatih Çelmeli, Emmanuelle Jouanguy, Shen‐Ying Zhang, Marwa Chbihi, Jonathan Bohlen, Anya Rothenbühler, Jacinta Bustamante, Vivien Béziat, Adrian Gervais, Tom Le Voyer
article en
15 citations

Abstract

Human inborn errors of the type I IFN response pathway and auto-Abs neutralizing IFN-α, -β, and/or -ω 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-α2, -β, or -ω. As controls, we add a monoclonal antibody (mAb) blocking the type I IFN receptors and stimulated blood with IFN-γ (type II IFN). Of the molecules we test, IP-10 (encoded by the interferon-stimulated gene (ISG) <i>CXCL10</i>) 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-γ, 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.

Proceedings of the National Academy of SciencesVol. 121(40)
Centre National de la Recherche Scientifique (FR), Inserm (FR), Université Paris Cité (FR), University of Pavia (IT), Assistance Publique – Hôpitaux de Paris (FR), Antalya Eğitim ve Araştırma Hastanesi (TR), Hôpital Saint-Louis (FR), Istituti di Ricovero e Cura a Carattere Scientifico (IT), Institut des Maladies Génétiques Imagine (FR), Structure fédérative de recherche Necker (FR), Rockefeller University (US)
Howard Hughes Medical Institute, Fisher Center for Alzheimer's Research Foundation, Meyer Foundation, JPB Foundation, Fondation du Souffle, Ministère de l'Enseignement supérieur, de la Recherche et de l'Innovation, Institut des maladies génétiques Imagine, SCOR Corporate Foundation for Science, Agence Nationale de la Recherche, Institut National de la Santé et de la Recherche Médicale, Assistance Publique - Hôpitaux de Paris, Fondation pour la Recherche Médicale, King Abdullah University of Science and Technology, Stavros Niarchos Foundation, Università degli Studi di Pavia, Centre National de la Recherche Scientifique, King Abdulaziz City for Science and Technology, Hospital for Sick Children, Fondation Bettencourt Schueller, Assistance publique-Hôpitaux de Paris, National Institutes of Health, HORIZON EUROPE Framework Programme, National Center for Advancing Translational Sciences, CHIST-ERA
Good health and well-being
Openalex Percentile: Top 6%
interferon and immune responses
3.61
DOIOpen Access PDFOpenAlex
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