Researchers have identified DNA mutations in a gene that can sense viral RNA as a cause of the autoimmune disease lupus, according to Science Daily.
The researchers, who published their findings Wednesday in the journal Nature, suggested that this genetic cause could pave the way for the development of new treatments.
Lupus is one of the chronic autoimmune diseases characterized by inflammation in the organs and joints. It also affects the movement and the skin. In advanced cases, symptoms can be persistent fatigue and debility. There is no cure for lupus and the current treatments, such as immune-suppressors, work by dialing down the immune system to palliate the symptoms.
The researchers conducted whole-genome sequencing on the DNA of a Spanish child named Gabriela. She was diagnosed with severe lupus at the age of 7. The team found a single-point mutation in the TLR7 gene. They used CRISPR gene-editing in mice to confirm that the TLR7 mutation causes lupus.
The mice went on to develop lupus and showed similar symptoms, potentially providing evidence that the cause was TLR7 mutation.
Senior author Prof. Carola Vinuesa said, “It has been a huge challenge to find effective treatments for lupus, and the immune-suppressors currently being used can have serious side effects and leave patients more susceptible to infection. There has only been a single new treatment approved by the FDA in about the last 60 years.”
“This is the first time a TLR7 mutation has been shown to cause lupus, providing clear evidence of one way this disease can arise,” she added.
Prof. Nan Shen said, “While it may only be a small number of people with lupus who have variants in TLR7 itself, we do know that many patients have signs of overactivity in the TLR7 pathway. By confirming a causal link between the gene mutation and the disease, we can start to search for more effective treatments.”
Interestingly, other studies have shown that TLR7 mutation is also associated with some cases of severe COVID-19 infection, potentially explaining the delicate balance of the immune system.
The study’s co-author Dr. Carmen de Lucas Collantes said, “Identification of TLR7 as the cause of lupus in this unusually severe case ended a diagnostic odyssey and brings hope for more targeted therapies for Gabriela and other lupus patients likely to benefit from this discovery.”
Meanwhile, the team is now working with pharmaceutical companies to explore treatment options that target the TLR7 gene. They hope that targeting this gene could help patients with lupus.
Prof. Carola said, “There are other systemic autoimmune diseases, like rheumatoid arthritis and dermatomyositis, which fit within the same broad family as lupus. TLR7 may also play a role in these conditions.”