An international team of researchers has found a cause for the autoimmune disease lupus, with the discovery paving the way for the development of new treatments.
A chronic disease of the immune system, lyophilis causes inflammation in organs and joints, affects movement and the skin, and causes fatigue. In severe cases, symptoms can be life threatening.
There is no cure for the disease, which affects around 50,000 people in the UK, and current treatments are mostly immune-suppressors which work by dialling down the immune system to alleviate symptoms.
The scientists carried out whole genome sequencing on a Spanish child who was diagnosed with severe lupus when she was 7 years old. It is rare for a case with early symptoms to be caused by a single genetic cause.
The Centre for Personalised Immunology at the Australian National University carried out a genetic analysis and found a single point deletion in the TLR7 gene. The US and China Australia Centre of Personalised Immunology (CACPI) at Shanghai Renji Hospital identified other cases of severe lupus where this gene was also altered.
The team used gene-editing to confirm the cause of the disease. The mice that developed the disease showed the same symptoms as the mice that did not. The mouse model was named by the young girl who was at the center of this discovery.
Carola Vinuesa, senior author and principal investigator at the Centre for Personalised Immunology in Australia, co-director of CACPI, and now group leader at the Crick, says that it has been a huge challenge to find effective treatments for lupus. The FDA has only approved one new treatment in the last 60 years.
This is the first time that a TLR7 mutation has been shown to cause a disease.
While it may only be a small number of people with lupus who have variant in TLR7 itself, we do know that many patients have signs of over activity in the pathway. We can start to search for more effective treatments if we can confirm a link between the genes and the disease.
The researchers found a way to make the TLR7protein bind more easily to the guanosine component of the nucleic acid. This increases the immune cell's sensitivity and it is more likely to mount an attack against healthy tissue.
Some cases of severe COVID-19 infections are associated with some cases of less active TLR7 because of the delicate balance of a healthy immune system.
The work may help explain why women are more prone to the disease than men. Females have two copies of the gene while males have one. In females, one of the X chromosomes is inactive, but in this section of the chromosomes, the second copy is often incomplete. This means that females can have two functioning copies of the same gene.
Dr Carmen de Lucas Collantes, a co-author of the study, says that the discovery of the cause of the case of lupus will hopefully lead to more targeted therapies for the patients.
Gabriela, who remains in touch with the research team and is now a teenager, hopes that the finding will give hope to people with the disease. Hopefully the research can lead to a specific treatment that will benefit so many people who suffer from this disease.
The researchers are working with pharmaceutical companies to explore the development of new treatments that target the TLR7 gene. They hope that targeting this gene will help patients with related conditions.
Carola says that there are other systemic autoimmune diseases, like dermatomyositis, which fit within the same broad family as lupus. It is possible that TLR7 plays a role in these conditions.
Carola has started a new laboratory at the Francis Crick Institute to further understand the disease-causing mechanisms that occur downstream of key genes.
There are notes.
There are examples of studies on COVID-19.
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