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How a type of molecule may be the reason women have a higher risk of autoimmune disease

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Scientists say a molecule linked to the X chromosome may explain why women are at higher risk of developing autoimmune diseases. Cavan Images/Getty Images
  • Of all people living with an autoimmune disease, 80% are women.
  • Researchers say a specific molecule found only in females may explain the high rates of autoimmune disease in women.
  • Experts say the research could be a breakthrough in the field of autoimmune disease and could pave the way for interventions in the future.

Scientists say they may have made a breakthrough in uncovering what is behind the higher rates of autoimmune disease in women.

They say the difference may revolve around a type of molecule found only in females.

Research Trusted Source Cell Peer reviewed journal Go to source published today in the journal Cell by Stanford University researchers in California report that a molecule known as Xist may be driving female-biased autoimmunity.

“Four out of five patients with autoimmune diseases are women. This study showed that an RNA called Xist that is made only in female cells could be a major driver of autoimmunity. This understanding can help design new ways to diagnose and perhaps treat autoimmune diseases,” Howard Chang, PhD, the senior author of the study and a professor of dermatology and genetics at Stanford, told Medical News Today.

About 50 million people in the United States have one or more autoimmune diseases. Up to 80% Trusted Source PubMed Central Highly respected database from the National Institutes of Health Go to source of these people are women.

Many autoimmune diseases disproportionately impact women more than men. The ratio of females to males is 9 to 1 in lupus and in Sjorgen’s syndrome it’s as high as 19 to 1 Trusted Source PubMed Central Highly respected database from the National Institutes of Health Go to source .

The Stanford researchers say they have honed in on this disparity and narrowed it down to one of the most fundamental features differentiating the biological sexes.

“Doctors and scientists have wondered for decades about the female prevalence of autoimmune diseases. Sex hormones, different chromosome counts, and other factors like pregnancy were invoked. This research shows that a single female specific RNA is a major driver – a novel explanation to a longstanding mystery,” Chang said.  

RNA refers to ribonucleic acid, a type of molecule that exists in the majority of living cells and is similar to DNA.

The researchers found a particular RNA may play a role in the high rates of autoimmune diseases in women and it’s all because of the X chromosome.

X and Y chromosomes

Every biologically female mammal has two X chromosomes. Men have one X and one Y.

A person can live without a Y chromosome, as biological females do, but it’s not possible to live without an X chromosome. The X chromosome holds hundreds of important genes that hold the instructions for the creation of proteins.

However, having two X chromosomes can mean there is a risk of an overproduction of proteins, which can have consequences.

X-chromosome inactivation solves that problem. During this process, every single cell in a female shuts down the activity of one of the X chromosomes.

This is made possible by a molecule called Xist. While the gene for Xist is found on all X chromosomes, and therefore in both females and males, it is only actually produced in a matched pair of two X chromosomes. This is only found in females.

Following X-chromosome inactivation, odd combinations of RNA, DNA, and protein are formed. It is the development of these complexes that triggers a strong immune response in the body.

Xist molecule increased the severity of lupus in mice

One of the first indications of the development of autoimmunity is the presence of autoantibodies in the blood.

When the researchers examined blood samples of more than 100 people with autoimmune diseases they said they found autoantibodies to many protein complexes that are associated with Xist.

“Every cell in a woman’s body produces Xist. But for several decades, we’ve used a male cell line as the standard of reference. 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, a huge source of women’s autoimmune susceptibility, go unseen,” Chang said in a press release.

The researchers conducted some experiments on mice with lupus to examine the effect of Xist.

“The results showed that making Xist significantly increased the severity of lupus. We do not yet know about other types of autoimmune diseases, but we detected antibodies to the Xist RNA protein complex in 3 types of human autoimmune diseases,” Chang said.

There are more than 100 autoimmune diseases, in which the body’s own immune system launches an attack on its own cells, tissues and organs.

Generally, there is no cure for an autoimmune disease and some diseases require lifelong treatment.

A game changer for autoimmune diseases

Dr. Daniel Arkfeld is a rheumatologist with Keck Medicine of USC in California who was not involved in the new research.

He says the Stanford study is an important step forward in autoimmune disease research.

“It actually is very much I think, a game changer in rheumatology, the way we look at our immune disorders. To kind of unraveling the mystery of autoimmune disorders,” Arkfeld told Medical News Today.

He says it could pave the way for potential interventions in the future.

“I think gene manipulation… will be coming in the future as well, which may target the chromosomal expressions a little bit more,” Arkfeld added. “We’re finding these antibodies present years before they were ever activating to disease, so there’s a lot of time, you could probably control things before they would ever lead to any end organ damage.”

Autoimmune diseases are still a mystery

The Stanford researchers are just one of many teams all over the world trying to gain a better understanding of the mechanisms underpinning autoimmune diseases.

Experts say there is still a lot going unanswered.

“We know a lot about some diseases and we’ve got very good treatments for some diseases. I think that what we haven’t cracked, is this question of, can we prevent them? How do we prevent them? So many researchers, like myself… are looking at people before the onset of disease, and then looking at those populations around the world,” Ranjeny Thomas, a researcher in autoimmune disease at The University of Queensland in Australia who was not involved in the new study, told Medical News Today.

“They’re monitoring them, looking at their immune system, why it fails, why it turns on itself and whether there are forms of immunotherapy or other forms of interventions that could help to prevent that from occurring,” Thomas added. “How can we actually prevent these diseases from occurring? Because they’re so life changing. They’re chronic diseases and life threatening in many cases.”

This article originally appeared on Medical News Today.

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