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Why Are Autoimmune Diseases More Common in Women Than Men?

Margaret Lipman
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Updated: May 16, 2024
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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.

More about autoimmunity:

  • Before this study, published earlier this month in the journal Cell, scientists already suspected that having two X chromosomes was linked to autoimmune diseases, based on the elevated risk for people with Klinefelter syndrome (two X chromosomes and one Y chromosome).

  • Scientists have documented at least 80 autoimmune conditions. Most are chronic and difficult to treat, with few having a cure.

  • The incidence of specific autoimmune disorders varies greatly. For example, 90% of lupus patients are women, whereas type 1 diabetes is more common in men than women.

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Margaret Lipman
By Margaret Lipman
With years of experience as an educator, Margaret Lipman produces thoughtful and informative content across a wide range of topics. Her articles cover essential areas such as finance, parenting, health and wellness, nutrition, educational strategies. Margaret's writing is guided by her passion for enriching the lives of her readers through practical advice and well-researched information.
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Margaret Lipman
Margaret Lipman
With years of experience as an educator, Margaret Lipman produces thoughtful and informative content across a wide range...
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