The immune system of women is more reactive than that of men, but this vigor comes at a price.
An immune hyperactivity indeed increases the risk of autoimmune diseases, where the body attacks its own tissues. Lupus, for example, affects nine women for every man. Yet the biological causes of this imbalance remained unclear. A large study conducted on more than a million immune cells has just shed light on hidden genetic differences between the sexes.
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Researchers from the Garvan Institute and UNSW Sydney analyzed 1.25 million immune cells from nearly a thousand healthy volunteers. Using single-cell sequencing technologies, they were able to observe the activity of each cell individually. The results revealed marked differences: men have more monocytes, first-line cells, whereas women have more B lymphocytes and regulatory T cells, with stronger inflammatory activity.
The study highlighted more than 1,000 genetic switches that control gene activity. Contrary to expectations, the majority of these switches are not located on the sex chromosomes X or Y, but on the autosomes, the chromosomes shared by both sexes. This indicates that immune differences between men and women are far more subtle than previously thought.
Several of these switches were directly associated with the risk of systemic lupus erythematosus. The researchers identified genetic variants that increase the activity of two genes linked to this disease in women. This discovery provides a clue to understanding why lupus strikes women far more often. The exact mechanisms remain to be explored, but these results open a new avenue for research.
These findings could transform the way autoimmune diseases are treated. Currently, treatments are often generic, but researchers advocate for personalized approaches. As Dr. Seyhan Yazar, lead author of the study, explained, "male and female autoimmune diseases may not be the same, and neither should the way we treat them." Precision medicine, taking into account the patient's sex, is therefore necessary to improve the efficacy of therapies.
This study, published in
The American Journal of Human Genetics, demonstrates that sex is an essential biological variable for understanding immunity and developing tailored treatments. The path toward truly personalized medicine requires taking this into account.