Exploring The Role Of IFNa In Autoimmunity And Infection



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. Digital ELISA IFNα protein measures correlated well with functional activity and IFN-stimulated gene expression, in contrast to IFNa protein measures by more conventional ELISA based methods. We have also used this approach to show the importance of early IFNa in COVID-19 patients, the response of which can be blunted by neutralising auto-antibodies against this cytokine often leading to critical diseases. The use of ultrasensitive assays for the study of IFNα proteins in patient samples highlights the insights that can be obtained from translational and clinical studies in autoimmunity and viral infection

Key Learning Points:

  • The importance of using sensitive and qualified immunoassays to measure IFNa in patient samples
  • Auto-antibodies can mask cytokine measures
  • Type I interferons are critical for early innate immune responses in COVID-19

About the Speaker:

Darragh Duffy, Head of the Translational Immunology Lab at the Institut Pasteur

Dr Darragh Duffy leads the Translational Immunology Unit at the Institut Pasteur in Paris and is co-coordinator of the LabEx Milieu Interieur project. The overall goal of his research is to better understand the fundamental mechanisms behind inter-individual differences in immune responses and apply these discoveries to relevant clinical questions. To do this they use cellular mechanistic models, population immunology cohorts, and experimental clinical studies in infection and autoimmunity, and work closely with clinical collaborators with the goal that the research findings will help to develop new patient management strategies.