Scientists Find a Genetic Cause of Lupus—Gain-of-Function Point Mutation in Innate Immune Response Gene Toll-Like Receptor 7 (TLR7), Which Normally Senses Viral RNA

An international team of researchers has identified a DNA mutation in a gene whose protein is normally involved in sensing viral RNA, as a cause of the autoimmune disease lupus, with the finding paving the way for the development of new treatments. Lupus is a chronic autoimmune disease that causes inflammation in organs and joints, affects movement and the skin, and causes fatigue. In severe cases, symptoms can be debilitating and complications can be fatal. There is no cure for the disease, which affects approximately 50,000 people in the UK, and current treatments are predominantly immune-suppressors which work by dialling down the immune system to alleviate symptoms. In their study, published in Nature today (April 27, 2022), the scientists carried out whole-genome sequencing on the DNA of a Spanish child named Gabriela, who was diagnosed with severe lupus when she was 7 years old. Such a severe case with early onset of symptoms is rare and suggests a single genetic cause. In their genetic analysis, carried out at the Centre for Personalised Immunology at the Australian National University, the researchers found a single point mutation in the TLR7 (Toll-like receptor 7) gene. Via referrals from the US and the China Australia Centre of Personalised Immunology (CACPI) at Shanghai Renji Hospital, they identified other cases of severe lupus where this gene was also mutated. The open-access Nature article is titled “TLR7 Gain-of-Function Genetic Variation Causes Human Lupus.”