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  • Denis Pepin

Xist: The Hidden Culprit Behind Women’s Autoimmunity

Updated: Apr 1

A surreal and colorful image of human figures and cells, with a focus on the nervous system. The central figure is seated, showcasing a detailed nervous system highlighted in orange against a blue body. To the left, there are red spherical cells, possibly representing pathogens or immune cells. Another figure on the left appears to be made of crystal or glass, with an emphasis on its internal structure. A third figure on the right is running forward against a backdrop of a bright sun and cloudy sky over an ocean or large body of water. The image illustrates the complex interactions of Xist in women’s autoimmune responses.
The image shows a woman’s nervous system, which is affected by autoimmune diseases. Autoimmune diseases are more common and severe in women than in men, and a new study has found a possible reason for this. The study discovered that a molecule called Xist, which is only present in women, can trigger antibodies that attack the body’s own cells and proteins. This can cause inflammation and damage to the nervous system and other organs. The image also depicts some of the proteins that bind to Xist and are targets of autoantibodies. The image suggests that Xist is a hidden and powerful factor behind women’s autoimmunity.

For a long time, scientists have been baffled by the fact that women are more susceptible to autoimmune diseases than men. Autoimmune diseases are disorders where the body’s immune system mistakenly attacks its own healthy cells and tissues. There are over 100 different kinds of autoimmune diseases, such as lupus, rheumatoid arthritis, multiple sclerosis, and type 1 diabetes. These diseases affect a large number of people, with about 50 million Americans living with one or more autoimmune diseases. Women account for around 80% of those affected. However, the exact reasons for this gender gap have been elusive. A new study has uncovered a possible explanation for this phenomenon.

The study, which was published in the journal Cell on February 1, 2024, was led by Howard Chang, a professor of dermatology and genetics at Stanford University School of Medicine in California. The study investigated a molecule called Xist, which is only present in women. Women have two copies of the X chromosome, while men have one copy of the X chromosome and one copy of the Y chromosome. The X chromosome carries hundreds of genes that produce proteins. Having two copies of the X chromosome can lead to too much protein production, which can be harmful. Xist helps avoid this by shutting down one of the X chromosomes in women. This is known as X-chromosome inactivation.

However, the study found that this shutting down can also cause autoimmune diseases.

The study revealed that Xist can activate antibodies that bind to complexes of the Xist RNA and its protein partners. Antibodies are immune molecules that normally protect the body from infections. However, when they bind to Xist complexes, they can cause inflammation and damage to healthy cells and tissues. This can result in autoimmune diseases. The study also found that many of the proteins that bind to Xist are targets of autoantibodies, which are antibodies that attack the body’s own proteins. This indicates that Xist plays a major role in causing autoimmunity in women.

The finding of Xist’s role in autoimmune diseases has significant implications for medicine. It could help develop new tests that can diagnose these diseases earlier, allowing for quicker treatment. It could also help create new treatments that are more effective and specific for these diseases. For instance, drugs that block Xist or its protein partners could lower inflammation and autoantibody production. This could enhance the quality of life for millions of people with autoimmune diseases.

In conclusion, the discovery of Xist’s role in autoimmune diseases is a major breakthrough. It explains why women are more vulnerable to these diseases than men. It also opens up new opportunities for diagnosis and treatment of these diseases. While more research is needed to fully understand how Xist works in autoimmune diseases, this study is an important first step towards reducing the impact of these disorders.


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