Detection of interferon alpha protein reveals differential levels and cellular sources in disease.

Mathieu P. Rodero 1 Jérémie Decalf 2 Vincent Bondet 2 David Hunt 3, 4 Gillian I. Rice 5 Scott Werneke 2 Sarah L. Mcglasson 4, 3 Marie Alyanakian 6 Brigitte Bader-Meunier 6, 7 Christine Barnerias 8 Nathalia Bellon 9 Alexandre Belot 10, 11 Christine Bodemer 9, 7 Tracy A Briggs 5, 12 Isabelle Desguerre 8 Marie Frémond 1 Marie Hully 8 Arn M J M Van den Maagdenberg 13, 14 Isabelle Melki 1, 6, 15 Isabelle Meyts 16, 17 Lucile Musset 18 Nadine Pelzer 13 Pierre Quartier 6 Gisela M Terwindt 13 Joanna Wardlaw 3 Stewart Wiseman 3 Frédéric Rieux-Laucat 7 Yoann Rose 1 Bénédicte Neven 6 Christina Hertel 19 Adrian Hayday 20, 21 Matthew L. Albert 2 Flore Rozenberg 22, 23 Yanick J Crow 1, 24, * Darragh Duffy 2, *
Abstract : 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.
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Mathieu P. Rodero, Jérémie Decalf, Vincent Bondet, David Hunt, Gillian I. Rice, et al.. Detection of interferon alpha protein reveals differential levels and cellular sources in disease.. Journal of Experimental Medicine, Rockefeller University Press, 2017, 214 (5), pp.1547-1555. ⟨10.1084/jem.20161451⟩. ⟨pasteur-01534181⟩

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