Autoimmune diseases, like multiple sclerosis and lupus, occur when your immune system goes haywire and starts targeting your own body. These diseases affect women at much higher rates than men. Up to now, the reason why has been a mystery. A group of scientists from Stanford recently found that the cause may lie in the X chromosome, with a molecule called Xist. In female cells that have two X chromosomes (XX), Xist plays a key role to deactivate one X chromosome so that there’s only one X used. In male cells, which only have one X chromosome (XY), Xist is completely inactive. These researchers discovered that Xist itself can cause an autoimmune response.
To isolate the effects of the presence or absence of Xist, the researchers took male mice and added a modified version of Xist that forms a molecular complex that might induce an immune response, but that wouldn’t inactivate the entire X chromosome. Then, they compared those male mice to normal male and female mice, after giving them lupus. They were able to show that male mice who were given the modified Xist looked much more like the female mice in terms of organ damage and their immune response. The researchers also took blood samples from human patients with autoimmune diseases and found autoimmune antibodies that target many parts of the Xist complex, a key sign that Xist is truly influencing these diseases in humans.
This study is a huge discovery for understanding the mechanisms of autoimmune disease. As the researchers say in their article, doctors may be able to now track antibodies that target parts of the Xist complex to monitor the course of a patient’s disease. Having a more complete picture of the biology of these diseases may also lead to better treatments.
This study was led by Diana Dou, a postdoctoral scholar in the lab of Howard Chang, a professor of Dermatology and Genetics at Stanford University.
Corresponding Author: Alex Yenkin
Original Journal Article: “Xist ribonucleoproteins promote female sex-biased autoimmunity,” Cell
Press Article: “Lupus and Other Autoimmune Diseases Strike Far More Women Than Men. Now There’s a Clue Why,” Time
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