Why do autoimmune diseases affect women more than men?

Autoimmune diseases are known for disproportionately affecting women, with 70-80% of those diagnosed being women. Recently, a study led by Stanford University sheds light on why autoimmune diseases are more prevalent in women than in men through a molecule called Xist (pronounced as "exist").

While men typically have one X and one Y chromosome, women usually have two X chromosomes. The X chromosome is responsible for the production of many important proteins, but if twice as many of those proteins were produced through the presence of two X chromosomes, the overproduction would be lethal. This is where Xist comes into play: it inactivates one of each pair of X chromosomes so that only one set of X chromosome proteins would be produced.

Recent discovery shows that Xist generates odd combinations of molecular complexes that bind to it. These Xist complexes—long strands of RNA entangled with DNA and proteins—induce a chemical response reminiscent of autoimmune diseases. Researchers identified around 100 proteins that are part of these complexes and found them to be known associated with autoimmune disease

In a strain of lab mice susceptible to lupus, researchers found that male mice—whose Xist were activated—developed lupus at similar rates as female mice of the same strain, when they were injected with an environmental irritant associated with lupus. In contrast, the activation of Xist in male mice—from a strain that was resistant to lupus—did not induce those mice to develop lupus (as the females of that strain also rarely develop autoimmunity). Xist's role provides valuable insight into why autoimmune diseases are more prevalent in women, although it is clear that environmental factors and other genetic factors are also at play.

More research is still needed to understand the other factors that contribute to autoimmune disease development. To support the Autoimmune Registry, please join our registry or share it with a friend who has an autoimmune condition. Donations are also greatly appreciated!