The mutated gene that drives the autoimmune disease lupus has been discovered, giving hope to 50,000 UK sufferers that may have a cure on the horizon.
Scientists at London’s Francis Crick Institute discovered that a mutation in the TLR7 gene can drive the condition, and have begun working with pharmaceutical companies to find drugs to cure it.
Lupus is a chronic autoimmune disease that causes inflammation in organs and joints, affecting movement, causing skin rashes and fatigue. In severe cases, it can be fatal.
There is no cure for the disease, with treatment largely limited to drugs that suppress the immune system and help ease symptoms, but which can make patients vulnerable to other conditions.
The mutation increases the sensitivity of immune cells, making them more likely to misidentify healthy tissue as foreign or damaged and attack against it.
Carola Vinusa, senior author and principal investigator from the Center for Personalized Immunology in Australia (CAPCI), and now leader of the group at Crick, said: “This is the first time a TLR7 mutation has been shown to cause lupus, a clear evidence of from which this disease can arise.
“Finding effective treatments for lupus has been a major challenge, and the immune-suppressors currently being used can have serious side effects and make patients more vulnerable to infection.”
ten times more often in women
In a new study published in the journal Nature, scientists carried out whole-genome sequencing on the DNA of a Spanish child named Gabriella, who was diagnosed with severe lupus at the age of seven.
After discovering the mutation in TLR7 they looked for the same problem in other severe cases of lupus and found that other patients had the same variant.
They then confirmed that the mutated gene could cause lupus by introducing it into mice, which went on to develop symptoms of the disease.
Professor Nan Shen, co-director of CAPCI, said: “By confirming a causal link between gene mutation and disease, we can begin the search for more effective treatments.”
The study may also help explain why lupus is about 10 times more common in women than in men.
As TLR7 sits on the X chromosome, that means females have two copies of the gene while males have one.
‘Clinical Odyssey’
Typically in females, one of the X chromosomes is inactive, but the segment in which TLR7 sits, sometimes silencing the other copy is disturbed, leaving females with two working copies.
And scientists are now also eager to find out whether TLR7 also plays a role in other diseases, such as rheumatoid arthritis.
Dr Carmen de Lucas Colantes of the Ruber International Hospital in Madrid, a co-author of this study, says: “The identification of TLR7 as the cause of lupus in this unusually severe case ended the diagnostic odyssey and more for Gabriella.” brings hope to targeted therapies. And other lupus patients are likely to benefit from this discovery.”
The researchers are now working with pharmaceutical companies to explore the development or reuse of existing treatments, which target the TLR7 gene.
