Why do women get more autoimmune diseases than men?

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Sept. 1 2011 7:38 PM

Autoimmunity Is From Venus

Why do women have more problems like Sjögren's syndrome and lupus?

Venus Williams. Click image to expand.
Venus Williams withdrew from the U.S. Open this week

Venus Williams dropped out of the U.S. Open tennis tournament Wednesday, citing a recent diagnosis of Sjögren's syndrome, an autoimmune disease known to cause dryness of the mouth and eyes as well as fatigue and joint pain. Like most other autoimmune diseases, Sjögren's affects many more women than men. Why is that?

Nobody knows, but scientists have a few theories. The sex bias in autoimmune diseases, in which the body's immune system attacks its host, has been known for more than a century. (Women account for roughly three-quarters of all diagnoses.) One of the earliest explanations, and long the most prominent, blamed hormones for pumping up the female immune response. Testosterone tends to suppress the body's response to infection, while estrogens typically boost it. Since women have a more vigorous response, goes the argument, their immune systems might be more likely to become hyperactive. (Curiously, men don't seem to be any more susceptible to infection or inflammation than women.) Data to support these claims, however, have been inconclusive.

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A more recent explanation involves genetics. While men carry an X and Y chromosome, women carry two X chromosomes. And though most of the second X chromosome is "silenced," or deactivated, some of its genes are spared. As a result, women may express more genes from the X chromosome than men do, and a number of these play a major role in immunity. Some researchers believe this difference might explain at least some of the sex-bias in autoimmune disease.

Another intriguing idea revolves around a phenomenon known as microchimerism, the presence of someone else's cells in your body. During every pregnancy and birth, there's a significant exchange of cells between mother and child. In most cases, both mum and tot get rid of those cells within a few weeks after birth. Sometimes, however, that process is incomplete, and the foreign cells "implant" in their host, where they pose a constant challenge to the immune system. Over time, the low-grade battle between immune system and foreign cells can escalate and, in theory, could set off an autoimmune response. This can occur in either the mother or the child. Since children can be either sex but all mothers are female, women have more chances to develop microchimerisms: It can happen when being born, and then again each time they give birth. On the other hand, there's little evidence that women who have given birth are more likely to have an autoimmune disease than childless women.

Got a question about today's news?  Ask the Explainer.

Explainer thanks Norbert Gleicher of the Center for Human Reproduction.

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