Lupus' Genetic Cause Has Been Discovered

Lupus' Genetic Cause Has Been Discovered ...

DNA mutations in a gene that perceives viral RNA as a cause of the autoimmune disease lupus have been identified, thus paving the way for the development of new therapies.

Lupus is a chronic autoimmune disease that causes inflammation in organs and joints, affects movement and the skin, and causes fatigue. In severe situations, symptoms may be debilitating, and complications may ensue.

There is no cure for the illness, which has a population of around 50,000 people in the United Kingdom, and current treatments are predominantly immune-suppressors that work by dialling down the immune system to alleviate symptoms.

The researchers conducted whole genome sequencing on the DNA of a Spanish child named Gabriela, who was diagnosed with severe lupus at the age of seven. A such severe condition with early onset of symptoms is rare and indicates a single genetic cause.

The researchers used a single point mutation in theTLR7gene in their genetic research conducted at the Australian National University. Through referrals from the US and the China Australia Centre of Personalised Immunology (CACPI) at Shanghai Renji Hospital, they identified other instances of severe lupus, respectively.

The team used CRISPR gene-editing to produce a novel novel for mice to develop the disease and present similar symptoms, confirming that the TLR7 mutation was the cause. Gabriela, the young girl who shaped this discovery, named the mouse model and the mutation.

Carola Vinuesa, a senior author and principal investigator at the Centre for Personalised Immunology in Australia, and now group leader at the Crick, claims that it has been a huge challenge to develop effective therapies for lupus, as well as the immune-suppressors currently being used, which can have disastrous side effects and leave patients more susceptible to infection.

This is the first time a TLR7 mutation has been detected to cause lupus, providing clear evidence of one way this disease may be prevented.

Although it may only be a small number of people with lupus who have variants inTLR7self, we do know that many patients have signs of overactivity in the TLR7 pathway. Through the discovery of a causal link between the gene mutation and the disease, we can begin to search for more effective treatments.

The TLR7 protein is able to quickly connect to a nucleic acid component called guanosine, thus increasing the immune cell''s sensitivity, making it more likely to incorrectly identify healthy tissues as foreign or damaged and perpetrate an attack against it.

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

Females have two copies of the gene in this section of the chromosome, although males have one. This means females with a mutation can have two functioning copies.

Dr Carmen de Lucas Collantes, a co-author of this research claims that the identification ofTLR7as the cause of lupus in this unusually severe case had successfully ended a diagnostic odyssey and brings hope for more targeted therapies for Gabriela and other lupus patients who may benefit from this discovery.

Gabriela, who is still in contact with the research team and is now a teenager, claims that her findings will give hope to people with lupus and enable them to feel confident that they are not alone in fighting this battle. Hopefully the research will continue and conclude up in a specific treatment that can benefit so many lupus warriors who suffer this disease.

The researchers are now working with pharmaceutical companies to discuss the development or repurposing of existing therapies that target theTLR7gene. They believe that this gene might also assist patients with similar problems.

Other systemic autoimmune diseases, such as rheumatoid arthritis and dermatomyositis, have also incorporated into the same broad family as lupus. TLR7 may also play a role in these conditions.

Carola has launched a newlaboratoryat the Francis Crick Institute in order to better understand the disease-causing mechanisms that occur downstream of key mutations, such as those found on the TLR7 gene.

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