Ultra-sensitive detection of interferon alpha protein in human disease by digital ELISA

Nature.com Webcast
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Speaker:  Dr. Darragh Duffy, Institut Pasteur, Paris
Moderator: Dr. Jayshan Carpen, Moderator, Nature Research

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Type I interferons (IFNs) are essential mediators of antiviral responses and 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 this fundamental role in health and disease, the direct quantification of type I IFNs has been challenging until recently with proxy readouts such as gene expression utilized instead.

Using single-molecule array (Simoa) digital ELISA technology, coupled with high-affinity autoantibodies isolated from patients with biallelic mutations in the AIRE protein causing APS1/APECED, we are able to detect attomolar concentrations of IFNα in patient samples. Importantly, these antibodies enabled detection of all 13 IFN- α subtypes, and protein measurements 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 is enhancing our understanding of IFN biology and potentially improve the diagnosis and stratification of pathologies associated with IFN dysregulation, while providing novel tools to assess new therapeutic strategies.

During this webcast you will learn/our speaker(s) will address:

  • How digital ELISA enables direct quantification of IFNa protein in human samples
  • How application of this assay to different diseases enables a better classification of autoimmune diseases and potential patient stratification
  • Such low protein sensitivity can identify the cellular driver of autoimmune states