Garvan and UNSW researchers identify 1,000 genetic switches behind sex differences in immune cells

August 20, 2026 at 05:00 AM2 min

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Researchers at the Garvan Institute of Medical Research and UNSW Sydney have identified more than 1,000 genetic switches that behave differently in female and male immune cells, offering a new biological explanation for women's higher susceptibility to autoimmune disease. The findings, published in The American Journal of Human Genetics, show greater inflammatory pathway activity in female cells and come as lupus affects as many as nine women for every one man.

Key Facts

The study sequenced more than 1.25 million peripheral blood mononuclear cells from nearly 1,000 healthy participants in Australia's OneK1K cohort.
Female immune cells showed greater activity in inflammatory pathways, while males had larger proportions of monocytes.
Lupus affects as many as nine women for every one man.
The findings were published in The American Journal of Human Genetics.

Single-Cell Study

Researchers sequenced more than 1.25 million peripheral blood mononuclear cells from nearly 1,000 healthy volunteers in the OneK1K cohort. The OneK1K cohort is a major Australian research project investigating how genetics affects individual immune cells across a large population. Traditional bulk blood analysis measures average activity across a mixture of many cells and can hide differences in specific cell types. This is the first study to compare male and female immune differences at single-cell resolution on this scale.

Sex Differences in Immune Cells

Females had greater numbers of B cells and regulatory T cells, while males had larger proportions of monocytes. Female immune cells showed much more genetic activity associated with inflammatory pathways. Male gene activity was more strongly focused on fundamental cell maintenance and protein production. The more than 1,000 genetic switches behaving differently by sex are linked to greater inflammatory pathway activity in females.

Autoimmune Disease Implications

Autoimmune diseases occur when the immune system mistakenly targets the body's own healthy tissues. Lupus affects as many as nine women for every one man. The findings provide evidence that diseases can develop and present differently in males and females. Garvan's Dr Seyhan Yazar said the immune system needs to be studied with sex in mind, and overlooking these differences can bias treatment options.