Women's immune system genes operate differently from men's

Washington: Researchers have discovered that men and women use different switches to turn on many immune system genes, a finding that may explain the much higher incidence of autoimmune diseases, such as lupus and rheumatoid arthritis, in women.

Some genes are virtually always on while others sit unused for years at a time. Some genes can be always on in one person and always off in another. A minority of genes switch on and off.

Researchers from the Stanford University School of Medicine have used a new technology which makes it possible to study the molecules that regulate all of that switching in humans.

They found that the genes that switch on and off differently from person to person are more likely to be associated with autoimmune diseases.

They also found that women and men use different switches to turn on many immune system genes.

It's too soon to be sure, but that difference in activity might explain the much higher incidence in women of autoimmune diseases such as scleroderma, lupus and rheumatoid arthritis, researchers said.

The new technique, called ATAC-seq, that lets researchers sample living cells in real time, was developed by a team led by the study's senior author Howard Chang, professor of dermatology.

In the new study, researchers took ordinary blood samples from 12 healthy volunteers to measure how certain genes are switched on and off, and how that measure varied among individuals.

Chang's team also looked at how much change occurred at different times in the same volunteers. The researchers looked at specialised immune cells called T cells, which are easy to isolate from a standard blood test, easy for volunteers supply and an important component of the immune system.

Across the 12 healthy volunteers, 7 per cent of the genes were switched on in different patterns from person to person. For each person, these patterns persisted over time, like a unique fingerprint.

"But the single greatest predictor for genes' tendency to turn on and off was the sex of the person. In terms of significance, sex was far more important than all the other things we looked at, perhaps even combined," Chang said.

When the team measured gene activity levels from 30 of the top 500 genes the researchers expected would show gender-influenced activity, they found that 20 of the 30 genes showed significant differential activity between men and women.

The study will be published in the journal Cell Systems.