New Study Reveals Link Between X Chromosomes and Women’s Increased Risk of Autoimmune Disease
Women have long been known to be more susceptible to autoimmune diseases than men, but the reason behind this gender disparity has remained a mystery. However, a recent study published in the journal Cell has shed light on this issue, suggesting that the risk may be linked to how the body controls its X chromosomes.
Humans have two types of sex chromosomes: X and Y. While most females carry two X chromosomes in each cell, most males have an X and a Y chromosome. The X chromosome is larger and contains more genes that code for proteins. However, in individuals with two X chromosomes, only one needs to participate in protein production to prevent an overload of proteins in cells. To achieve this balance, one X chromosome in each cell is “silenced” in females during embryonic development.
This silencing process is carried out by a long molecule of RNA called Xist, which latches onto one X chromosome. However, it has been discovered that many proteins are prone to sticking to Xist, forming large complexes of RNA and proteins. These complexes can trigger an immune reaction in which the body produces antibodies against the proteins within them. This immune reaction may predispose females to autoimmune diseases.
Dr. Howard Chang, co-senior study author and a professor of cancer research and genetics at Stanford University, explained the significance of these findings: “So besides its [Xist] job in controlling gene activity, there’s really a major immunological imprint that maybe hadn’t previously been recognized.” This discovery opens up new avenues for research into treatments for autoimmune diseases.
Autoimmune diseases affect millions of Americans and are caused by a combination of genetic and environmental factors. While scientists have proposed various theories to explain why women are more susceptible to these conditions, none have been conclusively confirmed. Previous research by Dr. Chang and his colleagues suggested that the Xist complex may play a role in sex-biased autoimmunity, as many proteins associated with autoimmune diseases can bind to it. However, further study was needed to isolate the influence of Xist from other factors such as hormones.
To investigate this further, the research team genetically engineered two strains of male mice. One strain was genetically susceptible to autoimmune symptoms similar to those of lupus, while the other was resistant. Female mice in the lupus-prone strain exhibited more symptoms than male mice, leading the team to theorize that Xist would bring the males’ disease levels up to that of females.
In their experiments, the team introduced a special version of the Xist gene into the genomes of male mice. This version could be switched on but wouldn’t silence their only X chromosome. To induce autoimmune disease, the lupus-prone mice were exposed to a specific chemical. The results showed that male mice expressing Xist developed disease at a similar rate to females and had more severe disease than mice without Xist.
The researchers also analyzed blood samples from over 100 patients with autoimmune diseases, including lupus, and 20 individuals without autoimmune disease. They found that patients with autoimmunity had more Xist autoantibodies in their blood compared to those without autoimmunity. The types and numbers of autoantibodies varied among individuals and were disease-specific, which could potentially aid in the diagnosis and treatment of these conditions.
While carrying Xist doesn’t guarantee the development of an autoimmune condition, it may help explain the discrepancy in case counts between sexes. This study provides valuable insights into the role of X chromosomes in autoimmune diseases and paves the way for future research in this field.
It is important to note that this article is for informational purposes only and does not offer medical advice. However, these findings have the potential to contribute to advancements in diagnosing and treating autoimmune diseases, ultimately improving the lives of millions of individuals affected by these conditions.
