WHY IS LUPUS MORE PREVALENT IN FEMALES?

-

 

WHY IS LUPUS MORE PREVALENT IN FEMALES?

A molecule associated with X chromosomes may contribute to developing lupus in females.

    


For years, researchers and clinicians have known that lupus, an autoimmune condition, occurs in women at a rate nine times higher than in men. Some of the factors that cause the disease's high prevalence in women have eluded discovery. Still, in a new study investigating the immune system processes in lupus and the X chromosome, Johns Hopkins Medicine researchers have uncovered answers about the disease's frequency in females.

Several dysregulated genetic and biological pathways contribute to the development of lupus and its varied symptoms of muscle and joint pain, skin rashes, kidney problems, and other complications throughout the body. One such pathway involves a protein in the immune system called toll-like receptor 7 (TLR7), which, in lupus, reacts to the body's own RNA. These molecules act as messengers of genetic information. TLR7's reaction to RNA triggers an immune response that damages healthy tissue.

In the full article, published in the October volume of the Journal of Clinical Investigation Insight, researchers honed in on this TLR7 immune response in lupus, looking specifically at how a piece of genetic material only found in women, known as X-inactive specific transcript (XIST), could trigger TLR7's immune system response. XIST is a type of RNA that plays a crucial role in inactivating one of the two X chromosomes found in female cells so that females do not have imbalanced gene expression.

"XIST has previously been implicated in autoimmunity, but more as something that could prevent autoimmune conditions like lupus, rather than drive the disease's development," says study author Erika Darrah, Ph.D., adjunct professor of medicine at Hopkins University School of Medicine. "Our findings show the opposite, that XIST actually plays a role in promoting autoimmunity -- increasing the susceptibility to lupus and its severity in women."

Using cellular experiments, the research team first tested whether XIST could bind to TLR7 and initiate the receptor's immune response. They observed that XIST could strongly bind to TLR7 and trigger the production of molecules called interferons, an immune system protein seen at high levels in lupus that contributes to tissue damage in this disease. Rather than protect from TLR7 and interferon's adverse effects on the body, these tests illustrated that XIST drove the process of an overactive immune response and contributed to lupus development.

"XIST has now taken on a different role, an alarm signal related to autoimmunity," says study author Brendan Antiochos, M.D., medicines Hopkins University School of Medicine. "The immune system activation through XIST and TLR7 is female-specific, helping explain the observation that lupus is so much more common in women compared to men."

To further study XIST's role in lupus, researchers also examined XIST levels in patients from two lupus cohorts. The team tested blood samples from patients at the Johns Hopkins Lupus Center for XIST levels. Also, it used publicly available data from another study that showed XIST and interferon levels in white blood cells taken from the kidneys of people with lupus. They assessed that the levels of XIST in the kidney correlate with higher interferon levels and that those with more XIST in their blood cells experienced greater disease severity and worsened lupus symptoms.

Darrah and Antiochos say these findings may implicate XIST in other autoimmune conditions more often seen in women. More research should be conducted to investigate this female-specific process.

Researchers also say that understanding XIST's role in lupus development may open the doors for creative therapies to treat the condition that targets the XIST-TLR7 pathway and provide additional explanations for patients who may wonder about the origins of their disease.

Additional study authors include Jonathan Crawford, Hong Wang, Daniela Trejo-Zambrano, Raffaello Cimbro, C. Conover Talbot Jr., Mekha Thomas, Ashley Curran, Alexander Girgis, John Schroeder, Andrea Fava, Daniel Goldman, Michelle Petri, and Antony Rosen, all from Johns Hopkins University School of Medicine.

C. Conover Talbot Jr. reports ownership of Merck & Co. common stock. Erika Darrah is an author of U.S. Patents 14/617,412 (awarded), 10,874,726 (awarded), 62/481,158 (provisional), 048317-642P01US (temporary), and 63/515,854 (temporary) and is a cofounder of Simmbion, LLC. Michell Petri receives research support from Eli Lilly & Co., GlaxoSmithKline, Janssen, and Aurinia. Erika Darrah and Raffaello Cimbro are current employees of AstraZeneca, and Jonathan Crawford is a current employee of Eli Lilly & Co. and may receive stock options.:

Comments

Post a Comment

Popular posts from this blog

BACK PAIN: TREATMENTS AND PREVENTION

-
Image
  BACK PAIN: TREATMENTS  AND PREVENTION Your back hurts. Join the club — you're one of millions dealing with this frustrating condition. Maybe it started after a long day at your desk or crept up slowly over the years. Either way, you're looking for answers. Let's cut through the noise and talk about what works. Why Your Back Might Be Complaining Think of your back as that friend who's always trying to tell you something. Sometimes, it's screaming for attention because you've been slouching at your desk for twelve hours straight. Other times, it's protesting your new workout routine without warming up. The usual suspects? Extra weight is significant — every pound you carry stresses your spine. Then there's how we live now: hunched over phones, slumped on couches, sitting for hours on end. Our bodies weren't built for this. But something that might surprise you: your mind has a more significant role in back pain than you'd think. Stress, anxiety, ...
Read more

DEPRESSION: CAUSES AND SOLUTIONS

-
Image
  DEPRESSION: CAUSES AND SOLUTIONS We've all had bad days, but depression is different. It's like wearing a heavy coat that weighs you down, even on the warmest days. And while we've come a long way in understanding this complex condition, there's still so much to learn. What Causes Depression? Your brain is like an incredibly complex orchestra. When everything's in harmony, it's beautiful. But sometimes, things get out of tune. Depression can stem from your genes, brain chemistry, life experiences, or, often, a mix of all three. Think of it this way: Some people inherit a tendency toward depression, just like they might inherit their grandmother's curly hair. But that's just part of the story. Your brain's chemical messengers (neurotransmitters) play their part,t too, along with things like chronic stress, trauma, or even ongoing health issues. Modern Treatment: Finding What Works for You Here's the good news: depression is treatable. The trick ...
Read more

Learn How the NEW Nutrition Facts Label Can Help You Improve Your Health

-
Image
  Learn How the NEW Nutrition Facts Label Can Help You Improve Your Health The US Food and Drug Administration (FDA) issued new regulations changing the  Nutrition Facts  label external  icon  on packaged foods. This is the first major change to the label since it was introduced in 1994. The changes are based on updated science, the most  recent dietary  recommendations, external  icon , and public input. Using the new label can help you choose foods for a healthy diet. The label will be required on all packaged foods made in the United States and imported from other countries. The new label is already appearing on packages. Most items will have the new label by January 1, 2021. What is changing? Calories & Fat Larger, darker letters make calories the easiest item to see on the new label. When it comes to health outcomes, the type of fat you eat matters more than the overall amount of fat. For this reason, the label will no longer show the per...
Read more