TY - JOUR
T1 - Detection of interferon alpha protein reveals differential levels and cellular sources in disease
AU - Rodero, Mathieu P
AU - Decalf, Jeremie
AU - Bondet, Vincent
AU - Hunt, David
AU - Rice, Gillian
AU - Werneke, Scott
AU - McGlasson, Sarah L
AU - Alyanakian, Marie-Alexandre
AU - Bader-Meunier, Brigitte
AU - Barnerias, Christine
AU - Bellon, Nathalia
AU - Belot, A
AU - Bodemer, Christine
AU - Briggs, Tracy
AU - Desguerre, Isabelle
AU - Frémond, Marie-Louise
AU - Hully, Marie
AU - van den Maagdenberg, Arn M.J.M
AU - Melki, Isabelle
AU - Meyts, Isabelle
AU - Musset, Lucile
AU - Pelzer, Nadine
AU - Quartier, Pierre
AU - Terwindt, Gisela M
AU - Wardlaw, Joanna
AU - Wiseman, Stewart
AU - Rieux-Laucat, Frédéric
AU - Rose, Yoann
AU - Neven, Bénédicte
AU - Hertel, Christina
AU - Hayday, Adrian
AU - Albert, Matthew L.
AU - Rozenberg, Flore
AU - Crow, Yanick
AU - Duffy, Darragh
PY - 2017/4/18
Y1 - 2017/4/18
N2 - 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.
AB - 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.
U2 - 10.1084/jem.20161451
DO - 10.1084/jem.20161451
M3 - Article
SN - 0022-1007
VL - 214
SP - 1547
EP - 1555
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 5
ER -
