Why Women Are More Prone to Autoimmune Diseases

February 11, 2024

by Cathe Friedrich

Did you know that autoimmune diseases, where the body’s immune system attacks healthy cells, affect over fifty million Americans? And for reasons scientists don’t fully understand, they disproportionately impact women – around 75% of those with autoimmune conditions are female.

A study published this month in Cell offers new clues that may help explain this gender imbalance. The research spotlights a unique RNA molecule called Xist that could confuse the immune system in women, making them more susceptible to these types of disorders. This new finding sheds light on why autoimmune conditions are more common in the female gender.

The Role of Xist in Autoimmune Diseases

Xist is an RNA molecule that serves a vital function. Women inherit two X chromosomes (XX), while men inherit one X and one Y (XY). Without the silencing effect of Xist, the double doses of X genes would wreak havoc in the body. During early development in women, it coats one of the two X chromosomes to inactivate it. This process, called X chromosome inactivation, prevents toxic levels of gene expression.

So, in every cell, Xist puts one X chromosome to sleep. This equalizes expression between males and females. But the new research shows this chromosome-silencing process may have unintended consequences.

How Xist Links to Autoimmunity

When Xist coats an X chromosome, it interacts with DNA and proteins, forming an unusual complex not seen elsewhere in the cell. This odd structure can confuse the immune system, causing it to mount an attack against its own tissues and organs.

The study found autoantibodies (immune proteins that target the body) against Xist complexes in the blood of female lupus patients. And when Xist was activated in male mice genetically engineered to express the gene, autoimmune symptoms developed faster compared to normal males.

Although we need more research, these findings suggest Xist can spur the onset of autoimmunity – but primarily in females. Males with just one X chromosome are less affected because they either don’t produce Xist or generate lower levels.

Other Contributing Factors

While the Xist molecule offers clues, researchers stress it’s not the only factor behind women’s higher autoimmune risk. Genetics and hormones like estrogen also play a role by influencing immune pathways.

And environmental triggers push the female immune system out of balance. Women tend to live longer on average, have more infections, and are more often exposed to triggers like chemicals in personal care products.

Still, the Xist discovery adds a new dimension to understanding gender differences in autoimmunity.

The Gut Factor in Autoimmunity

The trillions of bacteria in our guts are emerging as hidden puppet masters when it comes to autoimmune diseases like diabetes or multiple sclerosis. Though genetics load the gun, gut bugs seem to pull the trigger in many cases.

New research reveals how these microbial communities can make disease risk a tale of two genders. Male mice house gut bacteria that elevate testosterone levels, shielding them from autoimmunity. Transfer this “protective” microbiome to females, and their diabetes risk drops. Yet the opposite transfer leaves males more vulnerable.

It’s a bacterial behind-the-scenes drama where microbes direct immune system development, intestinal barrier security, metabolism, and hormones – fundamentally manipulating disease susceptibility versus resilience.

Though human studies are still limited, fecal transplants from healthy donors to patients hint at the potential for microbiome-targeted therapies. Probiotic cocktails, prebiotic foods, and stool substitutes may one day replace or complement approaches like chemotherapy to prevent or treat autoimmunity.

Environmental factors also influence who develops autoimmunity by disrupting digestive ecosystems. The Western high-fat, low-fiber diet promotes an imbalance linked to higher disease risk. Toxins, infections, and smoking take their toll too.

In the complex interplay between genes and environment, gut microbes are the invisible orchestrators determining who develops autoimmune disease. Learning to conduct rather than disrupt this microbial symphony may open avenues for preventing or treating these mysterious illnesses.

Potential Impact on Treatment

Currently, most autoimmune drugs broadly suppress the immune system, leading to side effects. But if further studies cement Xist’s role, it could spur therapies that target the molecule or its genetic signaling pathways.

“Maybe that’s a better strategy than just giving people higher and higher doses of steroids,” says Stanford geneticist Howard Chang, who led the Cell study.

The research also showed blood tests can detect autoantibodies against Xist complexes. So, alongside genetics, these antibodies could serve as predictive biomarkers to screen women early for autoimmune risk.

While we need more research, the Xist molecule may one day provide healthcare providers with an important new lever to pull in the fight against autoimmune illness. Understanding this RNA and its mechanisms inside women’s cells could be the key to locking up these diseases for good.

Lowering Your Risk of Autoimmune Diseases

There are ways to lower your risk of autoimmune disease:

Don’t smoke. Smoking is a major risk factor for autoimmune conditions like rheumatoid arthritis, lupus, and multiple sclerosis. Quitting can significantly lower disease risk over time.
Manage stress levels. Chronic stress takes a major toll on immune function, inflammation levels, and gut health – all contributors to autoimmunity. Practicing stress-relieving activities like yoga, meditation, or just setting aside daily relaxation time can help stabilize these systems.
Get enough sleep. Skimping on sleep promotes inflammation and throws off important immune cell functions. Aim for 7-9 hours per night to support healthy immunity. Establishing consistent bed and wake times can help optimize sleep quality too.
Exercise regularly. Regular physical activity keeps inflammation in check and may help regulate immune function. Aim for 30-60 minutes per day of moderate exercise like brisk walking, swimming, or cycling. Any movement is better than none.
Eat a nutrient-rich diet. Minimize processed foods and emphasize a balanced anti-inflammatory diet with plenty of fruits, vegetables, whole grains, healthy fats, and lean protein. Key nutrients like vitamin D, zinc, and omega-3 fatty acids support immune resilience.
Maintain a healthy gut. The gut microbiome directs immune function, so optimizing gut health can lower autoimmune risk. Consider taking a probiotic supplement and eating prebiotic fiber from foods like onions, garlic, bananas, and oats.
Know your family history. Many autoimmune conditions have genetic ties. Getting the right screening and being proactive with lifestyle changes can help those with higher inherited risk.

Implementing these strategies can tip the scales in your favor when it comes to avoiding autoimmune illness down the road. Small daily efforts add up to better lifelong immune defense and health.

Conclusion

As researchers learn to decipher this molecular code, we move closer to unlocking personalized prevention and treatment for the millions affected. For women especially, innovations like Xist-targeted therapies or predictive blood tests represent new rays of hope. While autoimmune conditions remain puzzling, progress continues.

And step-by-step, science is unraveling the mystery, so that one day in the not-too-distant future, we may finally witness the grand finale of these diseases – the moment the curtain closes and the lights go dark on autoimmunity forever.

References:

Wosen, Jonathan. “Clues from Mice Could Help Explain Why Women Face a Higher Risk of Autoimmune Disorders.” STAT, February 2024. https://www.statnews.com/2024/02/01/autoimmune-disease-research-why-women-at-higher-risk/.
‌Melinda Wenner Moyer. “Why Nearly 80 Percent of Autoimmune Sufferers Are Female.” Scientific American, September 2021. https://www.scientificamerican.com/article/why-nearly-80-percent-of-autoimmune-sufferers-are-
“What Are Common Symptoms of Autoimmune Disease?” https://www.hopkinsmedicine.org/health/wellness-and-prevention/what-are-common-symptoms-of-autoimmune-disease.
“Autoimmune Diseases: Causes, Symptoms, What Is It & Treatment.” https://my.clevelandclinic.org/health/diseases/21624-autoimmune-diseases.