Why Are Autoimmune Diseases More Common in Women Than Men?

Autoimmune diseases such as multiple sclerosis, lupus, and rheumatoid arthritis affect an estimated 24 to 50 million Americans. Broadly speaking, these conditions occur when the body's immune system mistakenly attacks healthy cells.

By a significant margin, most people with an autoimmune disease are female — around 80%. For decades, scientists have tried to find an explanation for this discrepancy with little success, though a recent study led by Stanford University researchers offers a very compelling theory.

While most men have one X sex chromosome and one Y sex chromosome, most women have two X chromosomes. This appears to put them at increased risk of autoimmune diseases. Specifically, female cells produce an RNA molecule called Xist that halts the activity of one of the X chromosomes. This process, known as X-chromosome inactivation, prevents the chromosome from expressing X-linked genes twice. However, the way that Xist shuts down the second X chromosome – by attracting clumps of proteins – appears likely to trigger an immune response when antibodies detect the unfamiliar molecular structures.

To investigate this link, the researchers genetically modified male mice to express Xist and attract the protein clumps, though without silencing the X chromosome. This resulted in an increased incidence of autoimmune conditions. Furthermore, the same auto-antibodies found in the blood of people with certain autoimmune diseases were produced by the male mice in the study.

Although the study suggests that Xist plays a major role in autoimmunity, it's not the only cause. After all, not all women who produce Xist suffer from autoimmune conditions, and some men have them, too, even without the presence of Xist. Yet when combined with environmental or genetic factors, the molecule appears to increase the likelihood of an autoimmune response.

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