A new study has uncovered hidden genetic differences in the immune systems of men and women. These differences may explain why women are more likely to develop autoimmune diseases like lupus.
Researchers at the Garvan Institute of Medical Research and UNSW Sydney found over 1,000 genetic switches that act differently in male and female immune cells. These differences seem to increase inflammation in females.
Uncovering Immune System Differences
Lupus affects up to nine women for every man, but the reasons for this have been unclear. This new research, published in The American Journal of Human Genetics, suggests that diseases can develop differently in men and women. The study also highlights the importance of including both sexes in medical research.
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Start Your News DetoxDr. Seyhan Yazar, the study's lead author, noted that immune systems need to be studied with sex in mind. Many studies still miss these differences, which can limit understanding of diseases and bias treatment options.
Scientists previously studied immune differences using bulk blood analysis. This method averages activity across many cells, which can hide important details. New single-cell technology allows researchers to look at individual immune cells in much greater detail. This study is the first to analyze male and female immune differences at this level.
The research team examined over 1.25 million immune cells from nearly 1,000 healthy people. These volunteers were part of the Australian OneK1K project, which studies how genetics affect immune cell behavior.
The results showed clear differences. Men had more monocytes, which are early immune responders. Their genes focused more on basic cell maintenance. Women had higher levels of B cells and regulatory T cells, with more activity in inflammation-related pathways.
Dr. Sara Ballouz, a co-senior author, explained that a highly reactive immune system helps women fight viral infections. However, this also makes them more prone to autoimmune diseases. Men's immune cells are less primed for inflammation, making them more susceptible to infections and certain cancers.
Genetic Clues for Future Treatments
A highly reactive immune system is always on alert. While this helps fight threats, it also increases the risk of the immune system attacking healthy tissue, leading to autoimmune disease.
By looking at individual cells, scientists found sex-specific genetic variations that earlier studies missed. They focused on genetic switches called expression quantitative trait loci, which control how strongly genes are activated. While these differences were thought to be mainly on sex chromosomes, most were found on autosomes, the non-sex chromosomes shared by both men and women. Over 1,000 such genetic switches were identified.
The team also linked some of these genetic controls directly to autoimmune disease risk. They found variants connected to female-biased activity in two genes related to systemic lupus erythematosus. This may help explain why lupus is more common in women.
Genetics are just one factor in autoimmune disease risk, along with hormones and other biological influences. However, these inherited genetic differences create an important baseline for how the immune system works.
Dr. Ballouz noted that this is the first time these differences have been shown at the genetic control level. This provides new insight into human immunity. The findings also suggest why common autoimmune treatments might not work equally for everyone. Identifying these distinct genetic pathways supports the need for more targeted therapies instead of broad immunosuppressive drugs.
Towards Personalized Autoimmune Treatments
Dr. Yazar stated that female and male autoimmune diseases may not be the same, and treatments should reflect this. Currently, many autoimmune diseases are treated with a "one-size-fits-all" approach. A more inclusive approach is needed.
Professor Joseph Powell, co-senior author, emphasized that understanding these fundamental biological variables is key for precision medicine. Treatments need to be tailored not just to the disease, but to how a patient's immune system works at a basic genetic level.
Deep Dive & References
The impact of sex on the immune system explored at the single-cell level - The American Journal of Human Genetics, 2026
