Disproportionate Autoimmunity in Women

Multiple sclerosis (MS) is an autoimmune disease that is characterized by the immune system's ability to attack the myelin sheath of axons in the central nervous system. This is called demyelination, and it affects neural signal transmissions. Those with this autoimmune disease suffer from a myriad of symptoms, namely muscle weakness, muscle spasms, paralysis, vision problems, cognitive impairment, etc. This disease affects people differently and can go from relapsing-remitting MS to secondary progressive MS. Those with progressive MS do not suffer from frequent attacks, but they experience constant symptoms and deterioration over time. As with other autoimmune diseases, we see more women being affected. I came across this article titled, “Stanford Medicine-led study shows why women are at greater risk of autoimmune disease,” and it talked about Dr. Howard Chang and how he has looked into the X-chromosome inactivation (gene Xist) and the many collaborator proteins that are bound to it in the hopes of understanding what is causing this autoimmunity to develop disproportionately in women.  

 

In the article “Xist ribonucleoproteins promote female sex-biased autoimmunity,” by Duo et al. (2024), they looked at Xist ribonucleoprotein complexes (RNP) that are created throughout the X-chromosome inactivation to see if they are a main cause of autoimmunity in women. To accomplish this, they induced transgenic Xist RNP formation in male lab mice. They compared normal male mice to the tgXist mice (the transgenic mouse could express Xist under doxycycline exposure). This study injected mice with pristane to chemically induce lupus-like symptoms. Their results showed that Xist RNP expression in the lab mice was enough to increase the severity of the autoimmune disease. They also found that it altered the gene expression in the B-cell and T-cell. It was the activation of Xist paired with the irritant (tissue damage/stress) that yielded the autoimmunity.  

 

These findings are very important because people with autoimmune diseases often have antibodies that target several key proteins connected to the Xist complex. If the immune system is reacting to these proteins before patients begin presenting symptoms, then these could prove to be useful markers that will aid in early detection.  

 

This search was prompted by the talk given by Dr. Chen, where they discussed their work using the inflammatory demyelination/remyelination model. Their study (Chen et al. 2023) found that the combined treatment of Sephin1 and BZA was more effective than either treatment alone in promoting the recovery of damaged fibers in the presence of inflammation. 

 

Together, these studies are hoping to uncover more about autoimmune diseases. One is focused on identifying autoantibodies to aid in earlier detection, while the other wants to help the development of therapeutic strategies.  

 

 

References: 

 

Duo, D. R. et al. “Xist ribonucleoproteins promote female sex-biased autoimmunity.” Cell, 187(3),733–749.e16. (2024). https://doi.org/10.1016/j.cell.2023.12.037 

 

Chen, Y. et al. Insights into the mechanism of oligodendrocyte protection and remyelination enhancement by the integrated stress response. Glia, 71(9), 2180-2195, (2023). doi: 10.1002/glia.24386 

 

Goldman, B. (2024, February 1). Stanford Medicine-led study shows why women are at greater risk of autoimmune disease. Stanford Medicine. https://med.stanford.edu/news/all-news/2024/02/women-autoimmune.html