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J Exp Med
Published

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

Authors

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 M J M 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

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.

PMID:28420733 | DOI:

UK DRI Authors

David Hunt

Dr David Hunt

Group Leader

Investigating how innate immune activation causes damage to the microvasculature of the brain

Dr David Hunt
Joanna Wardlaw

Prof Joanna Wardlaw

Group Leader and Clinical Director of the CVDR

Discovering how small vessel disease damages the brain and what we can do to prevent or treat it

Prof Joanna Wardlaw