New study sheds light on autoantibodies and immune system deficiencies in COVID-19

An international collaboration including Nils Landegren’s team at Uppsala University and SciLifeLab has revealed the genetic roots of autoantibodies against type I interferons, which are linked to severe COVID-19. Their study implicates genetic defects in the alternative NFκB pathway and a deficiency in thymic tolerance in the development of these autoantibodies.

A collaborative international research effort has offered insights into the genetic underpinnings of autoantibodies against type I interferons (IFNs) and their relevance for severe COVID-19. The study, with contributions from Nils Landegren, researcher at SciLifeLab at Uppsala University along with coworkers Axel Cederholm (PhD student in Landegren’s research group at IMBIM) and Daniel Eriksson (clinical geneticist and researcher at Uppsala University Hospital), has investigated the genetic factors associated with the development of type I interferon autoantibodies.

Building on previous findings that linked autoantibodies against type I interferons to severe COVID-19 outcomes, this research aimed to elucidate the genetic mechanisms responsible for the emergence of these autoantibodies. The study successfully identified genetic defects in the alternative NFκB pathway as amajor cause for the production of autoantibodies against type I interferon. They also find evidence of impaired thymic tolerance in these individuals. Landegren’s research group at Uppsala University has examined autoimmunity in individuals with NFκB pathway deficiencies and compared this to patients with autoimmune polyendocrinopathy syndrome type 1 (APS-1), a model disease characterized by impaired immune tolerance in the thymus.

Landegren’s team is working along several lines to explore the roles of cytokine autoantibodies in human disease. Their work on cytokine autoantibodies is supported by grants from Vetenskapsrådet and the Göran Gustafsson Foundation.

 “The interferon system serves as an alarm that triggers the body’s defense functions during an ongoing infection. It was discovered during the COVID-19 pandemic that approximately 1 out of 10 cases of severe COVID-19 can be linked to the presence of autoantibodies that block the interferon system. With the new study, an important step is taken to explain why these autoantibodies arise. I am very grateful for the support we have received from SciLifeLab and the Autoimmunity and Serology Profiling platform in particular”, says Nils Landegren.

In summary, this research provides insights into the genetic origins of autoantibodies against type I interferons, which increase the risk of severe COVID-19. Understanding the underlying genetic factors can help in developing strategies to better manage and prevent severe outcomes in affected individuals.

DOI: 10.1038/s41586-023-06717-x


Last updated: 2023-11-16

Content Responsible: Hampus Persson(