Paolo Rossi Castelli 26 May 2022 17 min read

The gene that triggers lupus has been identified

Important research published in the scientific journal Nature: a DNA mutation causes the TLR7 protein to malfunction, triggering errors in the immune system.

A few years ago a young Spanish girl named Gabriela received an unwelcome diagnosis: systemic lupus erythematosus, an autoimmune disease that affects the connective tissue of a range of organs and sometimes severely impairs the quality of life. There is virtually only one treatment based on generalised immunosuppression (putting a brake on the entire immune system) used to combat this disease, which can cause a range of side effects over time.

New discoveries about Lupus
Today and in the future, however, Gabriela, who is now a teenager, will probably be remembered for more positive reasons, because thanks to a thorough investigation of her genetic code, our understanding of lupus and approaches to treatment may finally be turning a corner.

An international team of researchers, led by Carola Vinuesa, principal investigator at the Centre for Personalised Immunology at the Australian National University and head of a laboratory at the Francis Crick Institute in London, published the results of their studies of the girl's DNA, which allowed them to identify a particular genetic mutation as a factor that can trigger the disease, in the scientific journal Nature.

The tests were then repeated on other sufferers from three different families. They showed similar results to Gabriela's and were also confirmed by tests on laboratory animals in which the same mutation had been induced.  

The mutated gene 'produces' an immune system protein called Toll-like Receptor 7 or TLR 7, which is already suspected of playing a decisive role in other autoimmune diseases. This protein is part of a group of molecules discovered by Luxembourg biologist Jules Hoffmann and American Bruce Beutler, joint recipients of the Nobel Prize for Medicine 2011.

Dangerous hyperactivity
The mutation mistakenly causes the TLR7 protein to become more active. This hyperactivity then increases the sensitivity of certain types of B- and T-lymphocytes in the immune system, increasing the likelihood that these 'guardians' of the body will mistakenly identify healthy tissue as foreign and trigger an attack to destroy it.

The discovery of the TLR7 mutation also appears to explain why the disease occurs nine times more frequently in women than in men. The gene is found on the X chromosome and there are two of these in women (men, on the other hand, have a Y chromosome, and only one X chromosome). Usually one of the X chromosomes remains inactive in women, to avoid duplication and damage, but this 'silencing' does not always work properly. In these cases, the effect of the TLR7 mutation is multiplied by two and it facilitates the emergence of the disease.

Lupus: paving the way for new treatments
If the role of the TLR 7 mutation is confirmed by further tests on a larger number of patients, new targeted and more specific treatments can be developed. Researchers are sure of this and are already working with several pharmaceutical companies. But that’s not all: new discoveries about lupus could also be useful, the researchers explain, in treating autoimmune diseases that share several features of this condition, like rheumatoid arthritis and other rheumatic diseases or dermatomyositis.

In Gabriela’s words
Finally, Gabriela's own comment is touching: ”I hope this discovery gives people with lupus hope and makes them feel less alone as they face this battle. I also hope that research can move forward and find specific treatment for the many fighters who are suffering from this disease”.


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Paolo Rossi Castelli

Journalist since 1983, Paolo has been dealing with scientific divulgation for years, especially in the fields of medicine and biology. He is the creator of Sportello Cancro, the site created by on oncology in collaboration with the Umberto Veronesi Foundation. He collaborated with the pages of the Science of Corriere della Sera for several years. He is the founder and director of PRC-Comunicare la scienza.