Body temperature may drive the higher risk of autoimmune conditions in women

Menstrual cycles and the menopause mean that a woman’s body temperature fluctuates more than a man’s, which may help explain why they’re much more likely to develop autoimmune conditions. Our body temperature affects our immune response and frequent fluctuations among women could affect the ability of their immune cells to differentiate between a dangerous invader and healthy tissue. “If women’s immune cells are experiencing more changes in temperature, they might be getting more overwhelmed and dysfunctional, which could contribute to an increased risk of autoimmunity,” says Elizabeth Maloney at the Pasteur Institute in Paris, who presented the findings at the Immunology of the Exposome conference at the Royal Society in London on 12 October. “It could be one piece of the puzzle in understanding sex differences in immunity.” Women generally mount stronger immune responses than men, making them less prone to infections. But this comes at a cost: women are up to four times more likely to develop autoimmune conditions, such as lupus or rheumatoid arthritis, which occur when the immune system overreacts to healthy tissue. Advertisement Such differences are due to several factors, including the genetics that determine sex. Most women have two copies of the X chromosome, which carries many immune genes, whereas most men have one X and one Y chromosome. This means women have greater genetic variation, strengthening their immune response. Hormonal differences also play a role. Oestrogen, the main sex hormone in women, generally bolsters immune system activity in those of reproductive age, while declining levels during perimenopause and menopause seem to accelerate inflammation, which plays a big role in autoimmunity. Men’s main sex hormone, testosterone, generally reduces inflammation. Now, Maloney and her colleagues have looked at the role of body temperature. They measured the core body temperatures, via a thermometer in the inner ear, of more than 900 adults, aged between 20 and 69. The group was roughly made up of an equal number of men and women, none of whom had a known autoimmune condition. The researchers also collected blood samples, which they exposed to a powerful immune-stimulating protein, a superantigen, from Staphylococcus aureus bacteria in a test tube. The one-off temperature readings were similar between the men and women. But among the women’s blood samples, a higher body temperature was linked to suppression of T-cells in response to the superantigen. T-cells are part of the adaptive immune system, which responds to threats like viruses, or – inappropriately – to molecules in the body that bring about autoimmune conditions. Among the women’s samples only, the researchers found that every 1 degree Celsius increase in body temperature was linked to a 36 per cent decrease in these cells’ ability to produce interferon-gamma. This is an inflammatory protein that enhances the ability of T cells to attack target cells, whether they’re healthy or infected. “This may be counterintuitive because we generally think of fever as stimulating inflammation,” says team member Darragh Duffy, also at the Pasteur Institute. But it seems there is also a mechanism by which high temperature can dial down the immune response to stop it getting out of hand, he says. One interpretation of the sex differences in the results it that the more frequent temperature fluctuations experienced by women caused their T cells to switch more often between suppressed and activated states, says Maloney. The core body temperature of pre-menopausal women rises by about 0.6 degrees Celsius, on average, after ovulation, then falls a day or two before menstruation. Perimenopause and menopause can also cause sudden increases in body temperature, manifesting as hot flushes. “Maybe the adaptive immune system is having to constantly change its set point, which sort of wears it out, and then that contributes to autoimmune risk.” “The findings add another dimension to sex differences in immune function,” says Sabra Klein at John Hopkins University in Baltimore, Maryland. Future studies should examine whether body temperature affects immune responses between men and women independent of their hormonal differences, says Klein. They could also track links between a woman’s menstrual cycle, body temperature and T cell response, says Maloney. For now, the team is working with another group of researchers to implement body temperature measurements in a vaccine trial starting next year, she says.