Nils Landegren research group

Autoantibody repertoire analysis

While genome sequencing provides insights into genetic diseases, comprehensive analyses of the reactivity of the immune system against self-proteins hold a key to understanding diseases caused by autoimmunity. Our group uses a set of complementary tools to achieve proteome-scale autoantibody repertoire analysis and high-throughput screening of large cohorts.

Cytokine autoantibodies

Protective immune responses depend on a fine-tuned interplay between multiple cell types and their communication through cytokines. Inborn errors of immunity are a well-known cause of susceptibility to infectious disease. Adding to this, there is now a rapidly increasing understanding of the roles played by cytokine autoantibodies in explaining why individuals may be at increased risk for infectious disease. Autoantibodies blocking type I interferon were recently found to underlie a severe disease course in COVID-19 and now a growing range of viral diseases. Inspired by these discoveries, we are exploring the broader roles of cytokine autoantibodies as causes of severe infection using a large-scale screening approach.

Cancer and autoimmunity

Our immune system serves not only to defend against invading microbes but also provides crucial protection against cancer, as proven by the groundbreaking success of checkpoint inhibitor cancer treatments. However, immune responses triggered by cancers can also lead to severe autoimmune manifestations known as paraneoplastic syndromes. Understanding the underlying mechanisms is critical for the diagnosis and treatment of paraneoplastic diseases, and can also provide insight into the protective antitumoral responses relevant to cancer treatment. We combine studies of tumor tissue and autoantibody repertoires in patients with paraneoplastic diseases to identify the events that trigger and shape autoimmunity.

Sex differences in autoimmunity

Women face a several-fold increased risk of autoimmune disease, whereas men tend to have worse outcomes from infections such as COVID-19. Our ERC-funded project SEXimmune aims to dissect the biological basis of sex differences in immune-related diseases. To better understand the roles played by sex hormones, we are conducting longitudinal immune analyses in women and men undergoing gender reassignment. We are also studying individuals with aberrant sex chromosome numbers to assess genetic factors underlying sex differences in immunity.

We are grateful to the European Research Council (ERC), Swedish Research Council, Swedish Cancer Society, Göran Gustafsson Foundation, Wallenberg Foundation, Cornell Foundation, and others, for the support of our research.

If you are interested in current openings in the lab, please send an email and CV to nils.landegren[at]imbim.uu.se.