The DNA of a girl with a severe form of lupus may have helped uncover a genetic cause for the autoimmune condition.
Lupus, which affects about 5 million people worldwide, occurs when an overactive immune system mistakenly attacks the body, triggering inflammation that can cause joint pain, rashes and extreme fatigue.
The underlying cause of lupus is somewhat of a mystery, making it difficult to develop treatments. 鈥淐urrent treatments are not curative and often they can be toxic,鈥� says at the Australian National University in Canberra. Most existing therapies dampen the immune system, leaving people more vulnerable to infections.
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To hunt for possible genetic causes, Brown and his colleagues sequenced the genome of a girl called Gabriela, who was diagnosed aged 7.
鈥淕abriela presented as an interesting case due to her early lupus diagnosis, meaning there was likely a greater genetic contribution to her lupus development,鈥� says Brown.
The sequencing revealed that Gabriela has a mutation in a gene called TLR7, which encodes a protein called toll-like receptor 7. This protein normally helps the immune system recognise foreign agents, enabling it to mount appropriate attacks against infections.
Male and female mice given Gabriela鈥檚 TLR7 mutation developed lupus-like symptoms. The mutation is thought to make it harder for the immune system to distinguish between foreign agents and healthy tissue.
TLR7 sits on the X chromosome, of which girls, women and transgender men have two copies and boys, men and transgender women have just one. This mutation may therefore explain why lupus is about 10 times more common in girls, women and transgender men.
However, such mutations have only been identified in two other people with lupus so far, suggesting the faulty gene isn鈥檛 the only cause of the condition. Other lupus cases may be triggered by altered proteins that sit downstream of TLR7 in the same immune-signalling pathway, says Brown.
His team is now exploring whether drugs that target TLR7 could treat lupus. 鈥淭he possibility for therapeutics is the really exciting thing,鈥� he says.
Nature
