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Women are more likely to be affected by autoimmune diseases, as their immune system attacks their own bodies. New research from Stanford University suggests that this gender bias may be due to the way the female body handles the extra X chromosome. Understanding this mechanism could lead to improved detection and treatment of autoimmune diseases that are challenging to diagnose and manage.
Autoimmune disorders, including lupus, rheumatoid arthritis, and multiple sclerosis, affect millions of Americans, with the majority of patients being women. One theory for this gender bias is the potential involvement of the X chromosome, as females have two X chromosomes while males have one X and one Y.
The latest research published in the journal Cell reveals that the extra X chromosome is indeed implicated, but in an unexpected manner. Xist, a specific type of RNA, plays a crucial role in the process of X-chromosome inactivation. In female cells, Xist silences one of the X chromosome copies to prevent an excessive expression of genes.
Dr. Howard Chang, a dermatologist at Stanford, discovered nearly 100 proteins associated with Xist. Many of these proteins are linked to skin-related autoimmune disorders, suggesting a potential connection between Xist and the activation of the immune system. While Xist alone may not cause autoimmune disease, it may contribute to the development of such conditions when combined with genetic susceptibility and environmental triggers.
In an experiment with male lab mice, researchers artificially induced the production of Xist without silencing the only X chromosome. The mice subsequently developed a lupus-like autoimmunity when triggered, similar to the levels observed in females. This suggests that Xist may play a role in autoimmune disease development, especially in the presence of environmental triggers.
In addition to animal studies, blood samples from 100 patients were analyzed, revealing autoantibodies targeting Xist-associated proteins not previously associated with autoimmune disorders. This suggests that standard tests for autoimmunity, which were developed using male cells, may not encompass the complete spectrum of autoantibodies in female patients.
While further research is needed, these findings offer potential insights into diagnosing and understanding autoimmune diseases with greater precision. Dr. Wherry, an immunologist from the University of Pennsylvania, emphasizes the significance of identifying the larger Xist complex in guiding disease patterns and diagnosis.
Dr. Chang suggests that understanding the process of RNA to abnormal cellular changes could be the next step in investigating potential interruptive strategies. This research opens up intriguing possibilities for developing new approaches for diagnosing and managing autoimmune diseases in the future.
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