·
·
Tech & Science
Researchers have identified over 1,000 genetic factors that distinguish male and female immune systems, shedding light on why women are more prone to autoimmune diseases like lupus. The findings emphasize the need for sex-specific approaches in medical research and treatment.
More than a thousand genetic elements have been found to operate differently in male and female immune cells, influencing disease susceptibility. This discovery comes from a large-scale single-cell analysis conducted by scientists at the Garvan Institute of Medical Research and UNSW Sydney.
The study focused on immune system variations that may explain why autoimmune diseases disproportionately affect women. Lupus, for example, impacts up to nine times more women than men, but the underlying biological causes have remained elusive until now.
Utilizing advanced single-cell technology, researchers examined over 1.25 million peripheral blood mononuclear cells from nearly 1,000 healthy individuals participating in the Australian OneK1K project. This approach allowed the team to observe immune cell activity at an unprecedented resolution, surpassing previous bulk blood analyses that averaged signals across many cells.
The data revealed that men possess more monocytes, immune cells that act as first responders, with gene activity geared toward cell maintenance and protein synthesis. In contrast, women exhibited higher quantities of B cells and regulatory T cells, alongside increased activation of inflammatory pathways.
“While this highly reactive immune profile gives females an advantage in fighting viral infections, it comes with a biological trade-off: a greater predisposition to autoimmune diseases,” explained Dr. Sara Ballouz, co-senior author and UNSW Senior Lecturer.
The investigation identified sex-specific genetic switches known as expression quantitative trait loci (eQTLs) that regulate gene activation levels. Contrary to prior assumptions that these differences primarily stem from sex chromosomes, most of these switches were located on autosomes, the chromosomes shared by both sexes.
Among these, several genetic variants were linked directly to female-biased activity in genes associated with systemic lupus erythematosus, providing new insights into the disease’s female predominance.
Researchers emphasized that genetics represent only one aspect of autoimmune risk, alongside hormones and other factors. However, the discovery of sex-based genetic regulation offers a foundational understanding of immune system function differences between men and women.
“This is the first time we have shown that these differences occur at the genetic control level, providing a new layer of insight into human immunity,” said Dr. Ballouz.
The findings also suggest why current autoimmune treatments may not be equally effective across sexes. The study advocates for developing targeted therapies that address specific genetic pathways rather than relying on broad immunosuppressive drugs.
Dr. Seyhan Yazar, the study’s first author, highlighted the necessity of recognizing sex differences in autoimmune disease management.
“Our findings add strong evidence that female and male autoimmune diseases may not be the same, and the way we should treat them may not necessarily be the same,” Dr. Yazar stated.
Professor Joseph Powell, co-senior author and director of Garvan’s Translational Genomics Program, stressed the importance of incorporating genetic sex differences into precision medicine.
“Treatments need to be tailored not just to the disease, but to how a patient’s immune system operates at a baseline genetic level,” Professor Powell remarked.
The study, titled “The impact of sex on the immune system explored at the single-cell level,” was published on 7 May 2026 in The American Journal of Human Genetics.
