A study published in Nature led by the Australian National University has identified a variant of the TLR7 gene as the cause of systemic lupus erythematosus (SLE). This finding paves the way for the development of more effective treatments.
The TLR7 gene has the ability to recognise the RNA of viruses and bacteria and activate the immune system to respond. A mutation in this gene can trigger an autoimmune reaction like the one that occurs in lupus.
Lupus is a chronic autoimmune disease that develops when the immune system attacks the body itself. Systemic lupus erythematosus (SLE) is the most common, but there are also cutaneous, drug-induced and neonatal lupus. Causative factors can be hormonal or environmental, such as oestrogens, infections, emotional and physical stress, pregnancy, various drugs and ultraviolet light from sunlight. It is a systemic disease, because it can affect any organ.
The symptoms are similar to the flu; for example, fever, fatigue, weight loss, headache and muscle and joint pain that may come and go. As yet, there is no cure for lupus, but analgesics, anti-inflammatories, corticosteroids, immunosuppressants and biological therapy can reduce the action of the immune system. However, immunosuppressants can increase the susceptibility of some patients to infections. Leading a good lifestyle, with a balanced diet, regular exercise, avoiding exposure to the sun and not smoking help to improve symptoms.
Researchers have suspected for years that the TLR7 gene had something to do with the development of systemic lupus, but until now it had not been confirmed. This became possible after the sequencing of the genome of a young Spanish woman diagnosed with the disease at the age of 7. As it was a serious and premature case, the scientists focused on the genetic cause and started from the hypothesis that perhaps it was a single mutation.
When analysing the genome, a variant of the TLR7 gene was found and considered as a possible cause of the disease. This variant produces a protein that has an affinity for certain molecules that inactivate it and, as a consequence, the disease manifests itself. In the laboratory, a genetic editing technique called CRISPR was used, which is notable for introducing the defective gene causing the disease into the cells of mice, then observing if they develop symptoms. The results showed that simply introducing this gene was enough for the process to occur.
90% of people affected by lupus are women. The involvement of this gene may help explain why. The TLR7 gene is located on the X chromosome and women have two copies, while men only have one so the chances of having the disease are much lower. In females, one of the copies is inactive, but in the part of the chromosome where the gene is found, the silencing is partial. Therefore, there are women who can have two copies of the functional gene. If it mutates, there is more chance of the disease appearing.
Identifying this gene and its causal relationship with lupus paves the way for the search for treatments directed at the TLR7 gene and for a possible cure. In addition, these treatments could also be applied to diseases included in the same family as lupus, such as rheumatoid arthritis and dermatomyositis, a muscle disease that causes inflammation and skin rash.