Scientists find genetic cause for autoimmune disease lupus

Scientists have found a genetic cause for lupus, the autoimmune disease which affects around 50,000 people in the UK.

Experts carried out whole genome sequencing on the DNA of a Spanish girl called Gabriela, who was diagnosed with severe lupus when she was just seven.

Such a severe case in a young child is rare and indicates a single genetic cause.

The team of scientists said they hope their finding will pave the way for new treatments, which have been lacking for the disease.

Lupus is a long-term condition that causes joint pain and skin rashes and has no cure.

The main symptoms are joint and muscle pain, extreme tiredness that will not go away, rashes (often over the nose and cheeks) and sometimes headaches, mouth sores and sensitivity to light.

Symptoms can flare up and settle down again, and treatments can include anti-inflammatory medicines like ibuprofen, hydroxychloroquine for fatigue and skin and joint problems, and steroids.

Two other drugs, rituximab and belimumab, are sometimes used to treat severe lupus and work on the immune system.

In the new study, published in the journal Nature, international researchers found a single point mutation in the TLR7 gene, which they said was causing lupus.

Using referrals from the US and China, they identified other cases of severe lupus where this gene was also mutated.

To confirm that the mutation causes lupus, the team used a type of gene-editing called CRISPR to introduce it into mice.

These mice went on to develop the disease and showed similar symptoms, providing evidence that the TLR7 mutation was the cause.

The mouse model and the mutation were both named Kika by Gabriela.

Carola Vinuesa, senior author and group leader at the Crick Institute in London, 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 (US Food and Drug Administration) 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.”

Professor Nan Shen, from the China Australia Centre of Personalised Immunology (CACPI) at Shanghai Renji Hospital, added: “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.”

The finding may also help explain why lupus is about 10 times more common in women than men.

TLR7 sits on the X chromosome, meaning  women have two copies of the gene while men have one.

Usually, in females one of the X chromosomes is inactive, but in this section of the chromosome, silencing of the second copy is often incomplete.

This means females with a mutation in this gene can have two functioning copies.

The mutation identified by the team causes the TLR7 protein to bind more easily to a nucleic acid component called guanosine and become more active.

This increases the sensitivity of the immune cell, making it more likely to incorrectly identify healthy tissue as foreign or damaged and attack it.