New genetic cause of lupus found

Researchers led by Min Ae Lee-Kirsch from the Department of Paediatrics and Adolescent Medicine, Faculty of Medicine, Technische Universität Dresden and scientists from the Max Planck Institute for Infection Biology, in collaboration with colleagues from the DRFZ and Charité-Universitätsmedizin Berlin, have discovered gene mutations in the protein UNC93B1. This protein plays a crucial role both in the signalling pathways for virus defence and in the development of Systemic Lupus Erythematosus (SLE). The results of the study were published in the journal “Science Immunology“.

The mutations in the UNC93B1 gene induce selective overactivation of the toll-like receptor TLR7, which specifically recognises certain ribonucleic acids (RNA), especially those originating from viruses. The overactivation of TLR7 causes incorrect recognition of the body’s own RNA, which triggers uncontrolled production of type 1 interferon and inflammatory processes. In parallel, the survival of self-reactive B cells is promoted, which produce autoantibodies against the body’s own cell components and thus enhance the autoimmune reaction. Medical blockade of overactive TLR7 could therefore be therapeutically effective.

It is also striking that people who lack functional UNC93B1 are susceptible to serious viral infections such as herpes simplex virus encephalitis or COVID-19. This observation emphasises the important role of UNC93B1 for a healthy immune system.