The body’s immune system is composed of several components that work together to fight against pathogens, infections, or anything that could jeopardize our health. In the case of autoimmune diseases, the immune system turns on the body and begins attacking healthy tissues and organs. These diseases can shut down or weaken entire systems of the body and can potentially be life-threatening. Scientists are not fully aware of what causes these types of diseases to occur, though many factors can affect a person’s vulnerability to them. One of those factors is gender. One in ten people in the US is affected by autoimmune diseases, and 80% of those affected are women. There have been many explanations proposed as to why this is true, but one study published in the scientific journal Cell aims to answer this question by examining the relationship between the genes within sex chromosomes and immune activity.
Every chromosome holds genes that are activated or deactivated in order to create proteins needed in different parts of the body. Women produce the same level of X proteins as men despite having two X chromosomes. This is because they possess a molecule called Xist, which clings to one of their X chromosomes like velcro and prevents the genes within the chromosomes from being activated. This is crucial to women’s health, as shutting down this second chromosome prevents an abundance of proteins from being produced, which can be detrimental to their development or adult lives. The aforementioned study aims to see if this gene blocker could be partly responsible for the higher prevalence of autoimmune diseases among women. One of the leads in this project, Dr. Howard Chang, noticed in his research prior that many of the proteins associated with autoimmune diseases were also responsible for helping Xist bind to the X chromosome.
In this study, Dr. Chang and his team examined a species of mice in which the females were at higher risk for lupus, while the males were not in the same danger. The scientists genetically engineered the male mice so they, too, would produce Xist molecules in their bodies. This genetic alteration caused cases of autoimmune diseases to increase tenfold among male mice. The results from this study were related to the fact that people who reported to have lupus or other autoimmune diseases had higher levels of antibodies related to Xist molecules. Dr. Chang proposes that the cycle of cell death within women could be the reason for this, as cells leave behind their proteins and molecules when they die. It is likely that the immune system views Xist as a foreign molecule and attacks it on a wider scale around the body, killing any cell with fragments of Xist on its surface.
One geneticist from the University of Pennsylvania, not involved in the study, stated that this is plausible but not completely realistic, as even men make antibodies related to Xist despite the molecule not being prevalent in their bodies at all. An endocrinologist at UCLA highlights the fact that the study performed by Chang and his team does not distinguish whether the presence of Xist triggers or merely intensifies autoimmune diseases. Some studies point toward the idea that since the X chromosomes possess genes responsible for producing proteins that communicate with immune cells, some genes are overexpressed and produce an abundance of signals that confuse the immune system and cause it to attack healthy cells.
In the end, there has not been a study conducted that can definitively answer the question of why women are far more susceptible to autoimmune diseases than men. The answer may lie within the X chromosomes, or it may not. For now, it remains a mystery to even the brightest minds in science. Finding an answer to this question will likely give us a different perspective on health than what we have now. Such understanding could even give way to the development of cures for autoimmune diseases, as now the only way to treat most of them is by shutting down the immune system altogether, thus leaving patients even more vulnerable.
