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

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 ELI SA technology, we recorded attomolar concentrations of IFN alpha in healthy donors, viral infection, and complex and monogenic interferonopathies. IFN alpha protein correlated well with functional activity and IFN-stimulated gene expression. High circulating IFN alpha levels were associated with increased clinical severity in SLE patients, and a study of the cellular source of IFN alpha protein indicated disease-specific mechanisms. Measurement of IFN alpha attomolar concentrations by digital ELI SA will enhance our understanding of IFN biology and potentially improve the diagnosis and stratification of pathologies associated with IFN dysregulation.