Scientists found a major clue why 4 of 5 autoimmune patients are women

In a paper published Thursday in the journal Cell, researchers present new evidence that a molecule called Xist — pronounced like the word “exist” and found only in women — is a major culprit in these diseases.

Better understanding of this molecule could lead to new tests that catch autoimmune diseases sooner and, in the longer term, to new and more effective treatments, researchers said.

Women typically have two X chromosomes, while men usually have an X and a Y. Chromosomes are tight bundles of genetic material that carry instructions for making proteins. Xist plays a crucial role by inactivating one of the X chromosomes in women, averting what would otherwise be a disastrous overproduction of proteins.

However, the research team found that in the process Xist also generates strange molecular complexes linked to many autoimmune diseases.

Although scientists conducted much of their work in mice, they made an intriguing discovery involving human patients: The Xist complexes ― long strands of RNA entangled with DNA and proteins ― trigger a chemical response in people that is a hallmark of autoimmune diseases.

Discovery of the role played by the Xist molecule does not explain how men get these diseases or why a few autoimmune diseases, such as Type 1 diabetes, have a higher incidence among men.

“Clearly there’s got to be more, because one-tenth of lupus patients are men,” said David Karp, chief of the division of rheumatic diseases at the UT Southwestern Medical Center in Dallas. “So it’s not the only answer, but it’s a very interesting piece of the puzzle.”

Autoimmune diseases have long proved difficult to address. Treatments are limited, and many of the diseases are chronic, requiring lifelong management. Most have no cure, leaving millions of Americans hoping that science will eventually offer better explanations for these ailments.

Stephanie Buxhoeveden was 25 when she began experiencing vision problems in her left eye and found herself unable to hold a syringe in her left hand — a critical tool for her nursing job. The reason: multiple sclerosis, an autoimmune condition in which the immune system attacks the protective covering of the brain, spinal cord, and optic nerves.

“I was overwhelmed and scared because I knew there was no cure,” the Virginia resident said. “All of these things that I had laid out, planned, and worked really hard for all of a sudden were completely up in the air and no longer guaranteed.”

Previous theories have suggested that the gender imbalance in these diseases might be caused by the main female hormones, estrogen and progesterone, or by the mere presence of a second X chromosome.

A tantalizing clue stemmed from men who have two X chromosomes and one Y chromosome, a rare condition called Klinefelter syndrome. These men run a much higher risk of suffering from autoimmune diseases, suggesting that the number of X chromosomes plays an important role.