DNA mutations in a gene that senses viral RNA as a cause of the autoimmune illness lupus have been identified, thus paving the way for further development.
Lupus is a chronic autoimmune ailment that causes inflammation in organs and joints, affects movement and the skin, and fatigue. In severe cases, symptoms may be debilitating, and complications may awn.
The condition, which affects around 50,000 people in the United Kingdom, has no cure, and current treatment are mostly immune-suppressors that work by dialing down the immune system to relieve symptoms.
Scientists carried out whole genome sequencing on the DNA of a Spanish child named Gabriela, who was diagnosed with severe lupus at the age of seven. A particularly severe case with early symptoms is rare and indicates a single genetic cause.
The researchers used information from the US and the Chinese Australian Centre of Personalised Immunology (CACPI) at Shanghai Renji Hospital to discover other cases of severe lupus.
The researchers used CRISPR gene-editing to investigate the lupus in mice. These mice continued to develop the disease and showed similar symptoms, confirming that the TLR7 mutation was the cause. Gabriela, the young girl who led the discovery, both named kika.
Carola Vinuesa, the senior author and principal investigator at the Centre for Personalised Immunology in Australia, is the director of CACPI and now director of the Crick, claims that effective treatment for lupus has been a huge challenge, and the immune-suppressors currently being used may have serious side effects, leaving patients more susceptible to infection. 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 demonstrated to cause lupus, revealing just how this disease might arise.
Although it may be a small number of people with lupus who have variants inTLR7itself, we do know that many patients have signs of overactivity in the TLR7 pathway. Through this information, we may begin looking for more effective treatments.
The TLR7 protein is able to connect more easily to a nucleic acid component called guanosine and become more active. This increases the immune cell''s sensitivity, making it more susceptible 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 instances of severe COVID-19 infection, highlighting the delicate balance of a healthy immune system.
Females have two copies of the gene, while males have one. 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.
A co-author of this research claims that determiningTLR7as the cause of lupus in this unusually severe case completed a diagnostic odyssey and paved the way for more targeted therapies for Gabriela and other lupus patients.
Gabriela, who works with the research team for the past 15 years, said: "I hope this finding will give hope to people with the disease and make them feel confident in their fight." Hopefully the research can continue and end up in a specific program that will benefit so many lupus warriors who suffer from the disease.
Researchers are now working with pharmaceutical companies to develop or repurpose existing treatments that target theTLR7gene. They hope that this gene might help patients with related conditions.
Unlike rheumatoid arthritis and dermatomyositis, other systemic autoimmune diseases, who fit within the same broad family as lupus, may be involved in these problems. TLR7 may also play a role.
Carola has established a newlaboratoryat the Francis Crick Institute in order to better understand the disease-causing mechanisms that occur downstream of key mutations, like the one found on the TLR7 gene.