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

J Exp Med. 2017 May 1;214(5):1547-1555. doi: 10.1084/jem.20161451. Epub 2017 Apr 18.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Enzyme-Linked Immunosorbent Assay / methods*
  • Humans
  • Interferon Regulatory Factors / blood
  • Interferon Regulatory Factors / cerebrospinal fluid
  • Interferon-alpha / blood*
  • Interferon-alpha / cerebrospinal fluid
  • Lupus Erythematosus, Systemic / blood
  • Sensitivity and Specificity
  • Severity of Illness Index
  • T-Lymphocytes / metabolism
  • Vesicular Stomatitis / immunology

Substances

  • Interferon Regulatory Factors
  • Interferon-alpha