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) ) 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.

DOI: 10.1073/pnas.2402983121, PMID: 39312669
Authors: Adrian Gervais, Corentin Le Floc’h, Tom Le Voyer, Lucy Bizien, Jonathan Bohlen, Fatih Celmeli, Fahd Al Qureshah, Cécile Masson, Jérémie Rosain, Marwa Chbihi, Romain Lévy, Riccardo Castagnoli, Anya Rothenbuhler, Emmanuelle Jouanguy, Qian Zhang, Shen-Ying Zhang, Vivien Béziat, Jacinta Bustamante, Anne Puel, Paul Bastard, Jean-Laurent Casanova