BIOBRIEF
Regulatory elements behave differently in male and female immune cells, clustering around inflammation pathways, a study in the American Journal of Human Genetics finds.
Lupus skews roughly nine-to-one toward women. That ratio has been clinical folklore for decades, but the genetic reason was missing. New single-cell work from Sydney's Garvan Institute of Medical Research and UNSW closes part of the gap: more than 1,000 stretches of DNA that act as dimmer switches for nearby genes behave differently in male and female immune cells, and they cluster in inflammation-related pathways. The same wiring that gives female immune systems a stronger defense against infection also widens the surface for the body to misfire against itself.
The study, published in The American Journal of Human Genetics00153-9), used single-cell sequencing to examine individual immune cells rather than averaging across blood samples, the standard approach in most prior immunology work. That resolution let the team catch cell-type-specific differences bulk methods miss.
"The immune system needs to be studied with sex in mind," said first author Dr. Seyhan Yazar of the Garvan Institute. Historically male-skewed study groups have biased the evidence base, she noted, with treatment options tuned on data that does not represent half the population.
A bioRxiv preprint and supporting Zenodo data accompany the paper.