Clinical Research Directory

Impact of the Presence of Anti-interferon Autoantibodies on the Viral Load in Severe Respiratory Infections

Sponsor: Hospices Civils de Lyon

Summary

Type I interferons (IFN-I) production is induced by the detection of viral molecules, such as RNA or DNA viral strands, through pattern recognition receptors (PRR) present on many immune cell types. Despite a minimal concentration, IFN-I secretion activate the secretion, by neighbouring cells, of more than 700 proteins with antiviral properties (inhibition of viral replication, destabilization of virus membranes, etc.). IFN-I constitute therefore one of the major first line of defence established by the immune system in response to viral infection. Briefly, during the Coronavirus disease (COVID-19) pandemic, several teams including ours, highlighted a lack of IFN-I response in approximately one in five individuals presenting a severe form of COVID-19. Interestingly, within a large part of them, in vitro investigations revealed the presence of autoantibodies presenting neutralizing capacities against alpha and/or omega interferons This finding confirms the deleterious role of anti-IFN-I autoantibodies on the antiviral immune response and the key role of IFN-I pathway regarding defences against COVID-19 infection. Furthermore, those observations pave the way to interesting research that would allow understanding the underlying pathophysiological mechanisms of severe viral respiratory infection. The research hypothesis are: i) IFN-I deficiency could induce severe forms of viral infections which could lead to intensive care admission ii) IFN-I deficiency could increase viral loads in nasopharyngeal samples, and be associated with protracted viral clearance iii) The frequency of viral co-infections may be higher in case of IFN-I antiviral pathway blockade, iv) severe forms of respiratory viruses' infections could be induced by other anti-cytokine autoantibodies. In addition to confirming research hypotheses recently mentioned, the aim of this clinical protocol will be to assess the impact of antiviral innate immune response alterations in severe respiratory infections.

Official title: Impact of the Presence of Anti-interferon Autoantibodies on the Viral Load in Severe Respiratory Infections in Intensive Care

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