Detection of interferon alpha protein reveals differential levels and cellular sources in disease.
Rodero MP, Decalf J, Bondet V, Hunt D, Rice GI, Werneke S, McGlasson SL, Alyanakian MA, Bader-Meunier B, Barnerias C, Bellon N, Belot A, Bodemer C, Briggs TA, Desguerre I, Frémond ML, Hully M, van den Maagdenberg AMJM, Melki I, Meyts I, Musset L, Pelzer N, Quartier P, Terwindt GM, Wardlaw J, Wiseman S, Rieux-Laucat F, Rose Y, Neven B, Hertel C, Hayday A, Albert ML, Rozenberg F, Crow YJ, Duffy D.
Source :
The journal of experimental medicine 2017
2017 sep 12
Pmid / DOI:
28420733
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.