Newly discovered sex-specific differences in the immune system help explain why women are more prone to autoimmune diseases than men, researchers say.
More than 1,000 genetic switches operate differently in female and male immune cells, driving higher overall activity of inflammatory pathways in females, the researchers reported in The American Journal of Human Genetics.
In autoimmune diseases - such as lupus, multiple sclerosis, and rheumatoid arthritis - the immune system mistakenly attacks the body's own healthy cells, resulting in chronic inflammation, tissue damage, and impairment of joints, skin, and organs.
The researchers analyzed more than 1.25 million immune cells circulating in the blood from nearly 1,000 healthy individuals in Australia. Using technology that allowed cell-by-cell analyses, they spotted sex-specific genetic variations that had been missed by previous “bulk” studies that measured average immune activity across a whole mixture of cells.
In particular, the researchers investigated genetic switches that are active in one sex but not the other - so-called ‘expression quantitative trait loci’ - that act like volume dials controlling how strongly a gene is turned on or off.
In females, genetic activity was heavily skewed toward inflammatory pathways, with higher levels of immune cells called B cells and regulatory T cells, they found.
In males, genetic activity was more concentrated on basic cellular maintenance and protein-building functions, with higher proportions of monocytes, cells that act as first immune responders.
“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,” senior study author Dr. Sara Ballouz of the University of New South Wales said in a statement. Male immune cells are less primed for inflammation, making men generally more susceptible to infections, she added.
“Our findings show that the immune system needs to be studied with sex in mind," study leader Dr. Seyhan Yazar of Garvan Institute of Medical Research said in a statement.
"Even though we know men’s and women’s immune systems differ, many studies still overlook these differences, which can limit how well we understand disease, and in turn bias treatment options.”
