Are Women's X Chromosome More Prone To Autoimmune Disorders?

Cisgender women are disproportionately affected by autoimmune disorders due to the X chromosome, a new study led by Stanford University researchers found. The study stated that four in every five autoimmune patients in the world are female. Scientists behind the study found traces back to a molecular coating typically found on half of a woman’s X chromosomes but not in male cells. The coating, a mix of RNA and proteins, can themselves cause discrepancies in the immune system, the study found.

Earlier, researchers had implicated that sex hormones and genetic mutation on the X chromosome are drivers of the autoimmune disparity. However, the new findings published in Cell Press could point to new diagnostic and therapeutic opportunities, scientists behind the study said.

Experts Convene For New Findings

The immune system protects our body from external harm caused by bacteria, parasites, viruses, etc. However, in some cases, the immune system attacks healthy cells in our body, leading to autoimmune disorders. Some common autoimmune disorders include Type 1 diabetes, Psoriasis, Rheumatoid arthritis, and Lupus among others. 

Studies have observed that cisgender women are more likely to be affected by these disorders, making up 80% of autoimmune patients. One of the researchers behind the recent study, geneticist and dermatology expert Dr Howard Chang, said, "As a practising physician, I see a lot of lupus and scleroderma patients because those autoimmune disorders manifest in the skin. The great majority of these patients are women."

A mixture of RNA and proteins are central to a developmental process called X-chromosome Inactivation. In this, long strands of RNA known as XIST (pronounced ‘exist’) coil around the chromosome, attracting dozens of proteins to form complexes that effectively muzzle the genes inside.

In some cases, some genes escape X inactivation, which causes autoimmune conditions. In previous studies, researchers also found that the XIST molecule itself can initiate inflammatory immune responses. Almost ten years ago, Dr Chang noticed that many of the proteins that interact with XIST were targets of misguided immune molecules called autoantibodies.

Because the XIST molecule is normally expressed only in XX cells, the study concluded that this could be the reason for the skew in autoimmune diseases affecting women. "That male cell line produced no Xist and no Xist/protein/DNA complexes, nor have other cells used since for the test. So, all of a female patient's anti-Xist-complex antibodies are a huge source of women's autoimmune susceptibility," Dr Chang said.