Sex Differences in Immune System Reactions May Be Reason Diseases Like Lupus Target Women

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by Chris Comish |

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Men and women respond differently to infections, a gender difference in immune responses that could help explain why some autoimmune diseases, such as systemic lupus erythematosus (SLE) and multiple sclerosis, are more likely to afflict one sex than the other. A review article by Sara Reardon, a science writer, explored this idea. It was published in Nature, and titled “Infections reveal inequality between the sexes.”

SLE is much more prevalent in females than males, possibly due to differences in sex hormone metabolism. Only 4 percent to 18 percent of men have the autoimmune disease, supporting the idea that each sex has distinct immune reactions.

Gender-related differences in reactions to infection could be based on different immune system reactions due to evolution. Because women carry children, they may need a strong and rapid immune response to protect the developing fetus.

An early example of noted gender differences in reactions to infection occurred in 1992. A new measles vaccine killed infant girls in clinical trials taking place in Senegal and Haiti, but for reasons that remain unclear, boys were unaffected. The deaths led the World Health Organization to stop development of the vaccine.

Sex differences in immune responses have only recently been discovered, a failing likely due to the design of clinical studies, which rarely assess women and men separately. “It’s sort of an inconvenient truth,” said Linde Meyaard, according to Reardon’s article. “People really don’t want to know that what they study in one sex is different from the other,” added Meyaard, an immunologist at University Medical Center Utrecht in the Netherlands.

New regulations could help. In the U.S., National Institutes of Health (NIH) standards now require consideration of both males and females in laboratory experiments involving animals, and similar requirements are being applied in Europe. Scientists previously often only used male subjects, due to the less variability caused, for example, by menstrual cycles.

Including both genders in clinical trials is also emphasized by the NIH, although the data is not well-tracked, according to the U.S. Government Accountability Office (GAO). A 2015 report notes that the “GAO recommends that NIH examine and report more detailed data on women’s enrollment in NIH-funded studies, and collect, examine, and report data on the extent to which these studies include analyses of potential differences between women and men. NIH agreed with GAO’s recommendations and plans to take action to implement them.”

Hopefully, scientists will focus more on understanding immune differences between women and men, shedding further light on diseases that occur disproportionately in one gender, such as SLE.