A new study suggests that women may face a higher risk of developing autoimmune diseases due to the way their two X chromosomes are regulated, pictured above. (Image credit: vchal via Getty Images)
Women are four times more likely than men to develop autoimmune diseases, in which the immune system mistakenly attacks the body's own cells. Now scientists believe they have found an explanation: the increased risk in women may be linked to the way their bodies manage their X chromosomes.
Humans have two types of sex chromosomes: X and Y. Most women have two X chromosomes in each cell, while most men have one X and one Y. The X chromosome is larger than the Y and contains many more genes responsible for making proteins. However, in people with two X chromosomes, only one of them needs to be involved in protein production – otherwise, the cells can become overloaded with excess proteins. To avoid this, one of the X chromosomes in women is “suppressed” during embryonic development.
A long RNA molecule — the genetic equivalent of DNA — called Xist is responsible for this suppression by sticking to one of the X chromosomes. But it turns out that many proteins tend to bind to Xist, and these large RNA-protein complexes may predispose women to autoimmune diseases.
That's because such complexes can trigger an immune response that causes the body to produce antibodies against the proteins contained in the complexes, according to a new study in mice and people published Thursday (Feb. 1) in the journal Cell.
“So beyond [Xist's] function in controlling gene activity, there's a really important immunological aspect to it that may not have been recognized before,” Dr. Howard Chang, a co-author of the study and a professor of oncology and genetics at Stanford University, told Live Science.
These findings could open up new avenues for research into treating autoimmune diseases, he said.
Autoimmune diseases, which affect more than 23.5 million Americans, result from the interaction of genetic and environmental factors. Scientists have proposed many hypotheses to explain why women are more susceptible to these diseases, pointing to their hormones and microbes, but none of these theories have been definitively proven.
Previous studies by Chang and colleagues have shown that the Xist complex may influence sex-linked autoimmunity, as many proteins associated with autoimmune diseases can bind to it. However, Xist needs to be studied in isolation, without considering other factors such as hormones that could potentially obscure its influence.
To do this, the team genetically modified two strains of male mice to create Xist: one was genetically susceptible to autoimmune symptoms similar to those of lupus, while the other was resistant, serving as a control group. In the lupus-susceptible strain, female mice showed symptoms more often than males, so the team hypothesized that Xist might increase the incidence of the disease in males to that of females.
In their experiments, the team inserted a special version of the Xist gene into the genomes of male mice that could turn on but not suppress their single X chromosome. To trigger the autoimmune disease, the research required exposing mice predisposed to lupus to a specific chemical.
Sourse: www.livescience.com
