Women have been at a greater risk of autoimmune diseases such as multiple sclerosis, lupus, and rheumatoid arthritis, the reason for which has been a perennial medical mystery. A team of researchers at Stanford University is likely to be close to resolving this mystery.
A recent study suggests that understanding how the female body manages its additional X chromosome, compared to the male body which typically has just one X and one Y chromosome, could shed light on why women are more prone to certain disorders. These chronic conditions predominantly involve an immune system malfunction where it mistakenly attacks the body’s own cells and tissues.
Although the research, which involved experiments on mice, is in its early stages, the findings could potentially lead to new treatments and diagnostic approaches for these diseases, according to Dr. Howard Chang, the senior author of the paper published in the journal Cell on February 1.
Dr. Chang, a professor of dermatology and genetics at Stanford School of Medicine, initiated the study due to his observation that symptoms of autoimmune disorders often manifest as skin rashes.
There are over 80 autoimmune diseases affecting approximately 24 million people in the United States. These disorders occur when the immune system becomes confused and starts attacking the body’s own tissues, mistaking them for pathogens.
Montserrat Anguera, an associate professor at the University of Pennsylvania School of Veterinary Medicine, explains that while the immune response in autoimmune diseases resembles that of fighting off an infection, the ‘infection’ persists and leads to tissue damage.
Previous research has focused on the gender disparity in autoimmune diseases by examining sex hormones or chromosome counts. However, Dr. Chang’s research centered on the role of a molecule called Xist, which is absent in male cells. Xist is responsible for deactivating the second X chromosome in female embryos, preventing cells from being overwhelmed by the chromosome’s genetic information.
Testing the ‘significant role’ of Xist
Dr. Chang’s investigations led him to hypothesize that the proteins associated with Xist might trigger autoimmune diseases. To test this, male mice were genetically engineered to produce Xist, and when exposed to a chemical irritant mimicking lupus, they developed autoimmunity similar to female mice. Moreover, analysis of human blood serum samples from patients with autoimmune diseases showed elevated levels of autoantibodies in reaction to proteins associated with Xist.
These findings suggest a significant role for Xist in driving autoimmunity and potentially explaining why autoimmune diseases are more prevalent in females. However, researchers caution that this is just one piece of a complex puzzle, as environmental factors also play a significant role in autoimmune diseases.
Ultimately, the hope is that these insights could lead to improved diagnostic methods and therapeutic interventions for autoimmune diseases, accelerating the process of diagnosis and treatment.
