Scientists have explained why autoimmune diseases more often affect women
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About 80% of all cases of autoimmune diseases are recorded in women. The reason for the disproportionality lies in the X-chromosome. This information will help to find new diagnostic and therapeutic possibilities.
Previously, researchers believed that sex hormones and misregulation of genes on the X chromosome were the cause of the autoimmune disparity. But in the course of a new study published in the journal Nature, they found out the real reason for this phenomenon.
Thus, scientists have established that proteins that play a central role in X-chromosome inactivation can independently trigger immunological alarm bells.
Women have two X chromosomes, and men have X and Y, which determine sex. Each chromosome contains genes that produce proteins. They perform their own functions in cells.
| PHOTO: Spectral/Depositphotos |
According to the scientists, X-chromosome inactivation silences the activity of one X chromosome in most XX cells, making the genes linked to the X-chromosome the same as those in male-typical XY cells.
The process is purely physical: long “strands” of RNA, known as XIST molecules, wrap around the chromosome, attract dozens of proteins, and form complexes that effectively suppress the genes inside.
When hundreds of such molecules revolve around the X-chromosome, they completely “close” it. If a gene on the second X chromosome gets out of Xist’s control, it results in an excess of proteins that can be toxic. A number of proteins involved in autoimmune diseases also help Xist shut down the X chromosome, the scientists point out.
According to one of the authors of the study, Howard Chang, autoimmune diseases can occur during the normal process of cell death in a woman’s body. Many Xist molecules and proteins attached to them are released into the blood. So when an immune cell encounters Xist, it sees the attached proteins and can mistakenly start making antibodies against the Xist proteins.
To test this idea, Chang and his colleagues “induced” a lupus-like disease in mice and found that the animals that produced Xist had higher levels of autoantibodies. Their immune cells were also on high alert.
It is noteworthy that the same autoantibodies were found in blood samples of people suffering from lupus, scleroderma and dermatomyositis. This suggests that Xist and related proteins are “something our immune system cannot ignore,” the researchers said.
“Diagnostics targeting these autoantibodies can help clinicians identify and monitor various autoimmune disorders,” – says Montserrat Angera, a geneticist from the University of Pennsylvania in Philadelphia.
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