Andrés Pisono and Chen Zhang found that autoantibodies neutralizing type I interferons appear in 5% of critical influenza cases but not in mild disease. These antibodies completely blocked the antiviral effect of interferon in lab-grown airway tissue. The autoantibodies exist in 1% of people under 70 and up to 6% over 80, identifying a large at-risk group for severe pneumonia.
Hello everyone, my name is Andrés Pisono from the BIRPAT team of the CRI Lyon.
My name is Chen Zhang from Rockefeller University, and we're going to describe our JEM paper entitled Autoantibodies Against Type I Interferons in Patients with Critical Influenza Pneumonia. Since 2015, we have identified inborn errors of the type I interferon immunity that can cause both life-threatening influenza and COVID-19 pneumonia. Surprisingly, we found that autoantibodies neutralizing type I interferon can also cause severe COVID-19 function as a phenocopy of the genetic defects. In this study, we test the hypothesis that autoantibodies neutralizing type I interferon can also underlie severe influenza pneumonia. In a cohort of 279 patients with critical influenza pneumonia, we identify about 5% of the patients with autoantibodies that can neutralize interferon alpha N, or omega. We didn't find these autoantibodies in patients with mild influenza infections.
Using functional assays in reconstituted human airway epithelia infected with influenza virus, we showed that patient sera containing such autoantibodies completely and specifically abrogated the antiviral effect of exogenous Type I interferon. These autoantibodies are not only found in patients with viral infections. Indeed, they are common in the general population. Their overall prevalence is about 1% in people under 70 years and can reach 6% in people over 80. These people are therefore at higher risk of developing life-threatening influenza pneumonia or COVID-19. In summary, our study demonstrates that autoantibodies neutralizing type 1 interferon account for 5% of life-threatening influenza pneumonia and further improves our knowledge of the essential role of type 1 interferon immunity in the control of both influenza and COVID-19 infections.
