Detection of interferon alpha protein reveals differential levels and cellular sources in disease
journal contributionposted on 14.10.2020 by Mathieu P Rodero, Jérémie Decalf, Vincent Bondet, David Hunt, Gillian I Rice, Scott Werneke, Sarah L McGlasson, Marie-Alexandra Alyanakian, Brigitte Bader-Meunier, Christine Barnerias, Nathalia Bellon, Alexandre Belot, Christine Bodemer, Tracy A Briggs, Isabelle Desguerre, Marie-Louise Frémond, Marie Hully, Arn MJM van den Maagdenberg, Isabelle Melki, Isabelle Meyts, Lucile Musset, Nadine Pelzer, Pierre Quartier, Gisela M Terwindt, Joanna Wardlaw, Stewart Wiseman, Frédéric Rieux-Laucat, Yoann Rose, Bénédicte Neven, Christina Hertel, Adrian Hayday, Matthew L Albert, Flore Rozenberg, Yanick J Crow, Darragh Duffy
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Type I interferons (IFNs) are essential mediators of antiviral responses. These cytokines have been implicated in the pathogenesis of autoimmunity, most notably systemic lupus erythematosus (SLE), diabetes mellitus, and dermatomyositis, as well as monogenic type I interferonopathies. Despite a fundamental role in health and disease, the direct quantification of type I IFNs has been challenging. Using single-molecule array (Simoa) digital ELISA technology, we recorded attomolar concentrations of IFNα in healthy donors, viral infection, and complex and monogenic interferonopathies. IFNα protein correlated well with functional activity and IFN-stimulated gene expression. High circulating IFNα levels were associated with increased clinical severity in SLE patients, and a study of the cellular source of IFNα protein indicated disease-specific mechanisms. Measurement of IFNα attomolar concentrations by digital ELISA will enhance our understanding of IFN biology and potentially improve the diagnosis and stratification of pathologies associated with IFN dysregulation.