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Scientists Discover Genetic Cause of Lupus, a Chronic Autoimmune Disease – Good News Network

May 8, 2022
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Scientists Discover Genetic Cause of Lupus, a Chronic Autoimmune Disease – Good News Network
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An international team of researchers has identified a cause of the autoimmune disease lupus within the DNA mutations of a gene that senses viral RNA—findings that will lead to the development of new treatments.

Currently there is no cure for the chronic autoimmune disease which causes inflammation in organs and joints and affects movement and the skin—sometimes with debilitating symptoms and complications that can be fatal.

Lupus affects around a quarter-million people in the US and UK, and current treatments are predominantly immune-suppressors which work by dialing down the immune system to alleviate symptoms.

But scientists recently reported carrying out whole genome sequencing on the DNA of a Spanish child named Gabriela, who was diagnosed with severe lupus when she was 7 years old. Such a severe case with early onset of symptoms is rare and indicates a single genetic cause.

In their analysis published April 27 in Nature, the researchers report finding a single point mutation in the TLR7 gene. Via referrals from the US and the Shanghai Renji Hospital in China, they identified other cases of severe lupus where this gene was also mutated.

LOOK: Marathoner Runner Stopped By Lupus is Racing Again Thanks to Amazing Treatment for Autoimmune Disorder

To confirm that the mutation causes lupus, the team used CRISPR gene-editing 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, the young girl being treated at the Centre for Personalised Immunology at the Australian National University.

“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,” said Carola Vinuesa, senior author, principal investigator, and leader of the new Autoimmunity Laboratory at the Francis Crick Institute where she will continue the research. “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.”

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It might be a small number of people with lupus who have variants in TLR7 itself, but many patients have signs of overactivity in the TLR7 pathway. By confirming a causal link between the gene mutation and the disease, researchers can start to develop more effective treatments.

The mutation the researchers identified 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 mount an attack against it.

Interestingly, other studies have shown mutations that cause TLR7 to become less active are associated with some cases of severe COVID-19 infection, highlighting “the delicate balance of a healthy immune system”.

10x More Likely in Females

The work may also help explain why lupus is about 10 times more frequent in females than in males.

As TLR7 sits on the X chromosome, females have two copies of the gene while males have one. Usually, one of the X chromosomes is inactive in females, 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.

“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,” says Dr. Carmen de Lucas Collantes, a co-author of the study.

CHECK OUT: We Can Now Use CRISPR Gene Editing on Ticks – to Fight Lyme Disease in Humans

The researchers are now working with pharmaceutical companies to explore the development of, or the repurposing of existing treatments, which target the TLR7 gene. And they hope that targeting this gene could also help patients with related conditions like rheumatoid arthritis and dermatomyositis, which belong to the same broad family as lupus.

Now a teenager who stays in contact with the research team, Gabriela expressed hope that the discovery will make people with lupus feel like they are not alone in fighting their battle. “Hopefully the research can continue and end up in a specific treatment that can benefit so many lupus warriors who suffer from this disease.”

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