Women are up to four times more likely to be affected than men autoimmune diseasethe following conditions occur: immune system It accidentally attacks your own body cells. Now, scientists think they know why. A woman’s outsized risk may be related to how her body controls her X chromosome.
There are two types of sex in humans chromosome: X and Y. Most women have two of their X chromosomes in each cell, while most men have an X and a Y. The X chromosome is larger than the Y and contains far more protein-coding genes. However, if a person has two X chromosomes, he only needs one to participate in protein production. Otherwise, cells can quickly become overwhelmed with too many proteins. To prevent this, in women, one X chromosome in each cell is “silenced.” during embryo development.
long molecules RNA — genetically cousins DNA — A system called Xist accomplishes this silencing by latching onto a single X chromosome. But it turns out that many proteins tend to stick to her Xist, and these large complexes of RNA and proteins can make women more susceptible to autoimmune diseases.
That’s because the complex can trigger an immune response that creates antibodies against the protein in the body, according to a new study in mice and humans published Thursday (February 1) in the journal Nature. cell.
“So, in addition to that, [Xist] There is indeed a major immunological signature that plays a role in controlling gene activity and that is probably hitherto unrecognized. ” Dr. Howard Chanco-senior study author and professor of cancer research and genetics at Stanford University told Live Science.
These findings could therefore open new avenues for research into treating autoimmune diseases, he said.
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Autoimmune diseases that affect Over 23.5 million Americanscaused by a combination of. genetically and environmental factors.scientists have proposed many theories Attempts have been made to explain why women are more likely to develop this condition, pointing to women’s hormones and microorganisms in and on their bodies, but none of these ideas have been conclusively confirmed.
previous research Chang et al. suggested that the Xist complex may cause gender-biased autoimmunity because many proteins associated with autoimmune diseases can bind to the Xist complex. But Xist had to be studied in isolation, excluding other factors such as hormones that could potentially mask its effects.
So the team created Xist by genetically engineering two strains of male mice. One strain of mice was genetically predisposed to autoimmune-like symptoms. lupus The other group was the resistant group, the comparison group. In lupus-prone strains, female mice are more likely to develop symptoms than male mice, so the team theorized that Xist could raise the level of disease in males to that of females.
In their experiment, the researchers sewed a special version of the Xist gene into the genomes of male mice. This gene can be switched on, but it cannot silence the only X chromosome. To stimulate the autoimmune disease, lupus-prone mice had to be exposed to a specific chemical.
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When Xist is activated and lupus is induced, the researchers found that male mice that expressed Xist developed the disease at a similar rate to females and had more severe disease than mice without Xist. It was confirmed.
But Chan said important controls require both environmental chemical triggers and a genetic predisposition to lupus. This made mouse experiments more relevant to humans.
“If someone is born with a genetic susceptibility, the presence of the Exist has some influence, but it is also this environmental trigger that is very important. [is necessary]”Having Xist does not guarantee that a person will suffer from an autoimmune disease. The Xist complex may just explain the disparity in the number of cases between men and women,” Zhang said. Ta.
To corroborate the mouse results, the researchers analyzed blood samples taken from more than 100 patients with autoimmune diseases, including lupus, and 20 patients without autoimmune diseases. They found that patients with autoimmunity had more Xist autoantibodies in their blood than people without autoimmunity.
The types and numbers of autoantibodies in different people are disease-specific and could help in the future diagnosis and treatment of these diseases, Zhang said. For example, capturing these autoantibody profiles could one day help doctors decipher what disease a patient has or predict the course of the disease, he said. Stated.
This article is for informational purposes only and does not provide medical advice.
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