Discovery of the lupus gene may lead to more effective treatment

Gabriella, a teenage girl from Spain, was diagnosed with severe lupus erythematosus (a chronic autoimmune disease in which the body’s immune system attacks its tissues and organs) at the age of seven.

Lupus, which is more common in women than in men, can cause inflammation of the skin, blood cells, joints, kidneys, brain, heart, and lungs. There is no cure for this disease and little is understood about the genetic causes of lupus. Current treatments are primarily immunosuppressive drugs, which work by dialing down the immune system to relieve symptoms.

According to international scientists who performed the whole genome sequencing of her DNA, Gabriella had severe lupus with early onset of symptoms — this is rare and indicates a single genetic cause. I am.

The Hudson Institute The work of the team was part of a multinational study published in a journal Nature.. In their genetic analysis Australian National UniversityResearchers have identified a new genetic cause, a mutation in a gene TLR7 — For this autoimmune disease. Through referrals from clinics in China and the United States, they identified other cases of severe lupus erythematosus in which this gene was also mutated.

TLR7 is an important sensor in our immune system, triggered by viral and bacterial RNA produced during infection. When involved, TLR7 activates a series of responses that facilitate the elimination of pathogens by immune cells. This is usually a transient inflammatory reaction.

TLR7 expert Michael Gantier, associate professor at the Hudson Institute for Medical Research, helped the team decipher how mutations promoted aberrant activation of this important immune sensor. When introduced into a mouse, TLR7 Mutations cause similar illnesses and symptoms, TLR7 It was due to a mutation. Both the mouse model and the mutation were named “Kika” by Gabriella, the central girl in this discovery.

“We, TLR7 The kika mutation increased susceptibility to guanosine, one of the key constituents of RNA. This means that in the absence of infections that this sensor normally detects, constant inflammation turns on abnormally, leading to autoimmune diseases, “Gantier said.

This study may also help explain why lupus is about 10 times more frequent in women than in men.As TLR7 Located on the X chromosome, females have two copies of the gene, while males have one.

Gabriella is still in contact with the research team, saying: Hopefully, research will continue and can end up with specific treatments that can benefit so many lupus warriors suffering from this disease. “

The study now provides a unique model to demonstrate the therapeutic effects of a new class of TLR7 inhibitors developed in collaboration with Noxofarm at the Hudson Institute, Gantier said.

“TLR7 is likely to hold the key to other autoimmune diseases and is also important for the immune response to mRNA vaccines. In addition to helping people like Gabriella, this study improves mRNA vaccines and they. May help reduce the number and severity of side effects. “

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