Hydroxychloroquine dose for autoimmune diseases
Tips on Autoimmune Diseases
Women are much more likely than men to develop autoimmune diseases like rheumatoid arthritis, multiple sclerosis and lupus.
Now, researchers have come up with a potential explanation for that—one that's rooted in genes that drive a person’s gender.
The female body has a complex means by which it handles the additional X chromosome, and it appears this process also renders some women more susceptible to autoimmune diseases, according to a report published Feb. 1 in the journal Cell.
This finding helps explain why women account for about 80% of all cases of autoimmune disease, in which the immune system turns on the body and attacks its tissues and organs.
More importantly, it could lead to better ways to detect and treat dozens of these disorders, researchers say.
“It’s a question that’s been irking immunologists and rheumatologists for the past 60 or 70 years,” Dr. Robert Lahita, a rheumatologist at the Hackensack Meridian School of Medicine in Nutley, N.J., told the journal Nature. Lahita was not involved in the study.
Biological sex is determined in mammals by the presence of two X chromosomes in every female cell. Males have just one X chromosome, paired with a shorter Y chromosome.
The X chromosome carries hundreds of active genes that support life, while the Y chromosome contains only a handful, researchers explained.
Unfortunately, having two X chromosomes increases the risk that the female body will produce a lethal double dose of these proteins, so nature has devised a way to deactivate one of them.
A special type of RNA
A special type of RNA called Xist—pronounced “exist"—is p produced by the extra copy in an XX pair.
Xist attaches to long sections of the extra X chromosome, cutting its genetic output to zero or close to it while leaving the other X chromosome alone to do its job.
Unfortunately, Xist also attracts odd combinations of proteins that clump together with it, and many of those close to 100 proteins are associated with autoimmune disorders, researchers realized.
That led them to suspect that the protein clumps created by Xist’s X-chromosome deactivation could be triggering autoimmune diseases in women. To test this, researchers inserted the gene for Xist into male lab mice bred to be susceptible to a lupus-like autoimmune disorder.
Xist could be turned on and off using chemicals, so it would only produce Xist when researchers wanted.
The mere insertion of the Xist gene had no noticeable effect on the male mice, researchers said. But once the Xist gene was activated, the typical protein clumps began forming in the male mice.
To see whether that made an autoimmune disorder more likely, researchers injected both those mice and non-bioengineered male mice with an irritant known to induce that lupus-like disorder.
It turned out that male mice with an active Xist gene developed the lupus-like condition at rates approaching those of females.
Because not all female or Xist-activated male mice developed the autoimmune disorder, it shows that some kind of trigger is required to activate such a disease, the researchers noted.
“We think that’s really important for Xist RNA to leak out of the cell to where the immune system gets to see it. You still needed this environmental trigger to cause the whole thing to kick off,” researcher Dr. Howard Chang, a professor of dermatology and genetics at Stanford University, told the Associated Press.
TIPS and Autoimmune DCS
But even the irritant trigger used in the mice didn’t cause all of them to develop the lupus-like disorder. That means that other genetic influences might come into play in determining whether a person develops an autoimmune disease, researchers said.
Because these Xist-linked protein clumps are tied to autoimmune disorders, researchers might be able to use them as the basis for a test to determine a person’s susceptibility.
Researchers examined blood samples from about 100 patients with autoimmune problems, looking for autoantibodies—antibodies that target the proteins that clump with Xist.
They found a list of autoantibodies that could potentially be used as a test for autoimmune susceptibility.
Gender bias in medical research could be one reason why it’s taken so long for scientists to figure this out.
Every cell in a woman’s body produces Xist,” Chang said in a university news release. 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 been used since the test. So, all of a female patient’s anti-Xist complex antibodies—a huge source of women’s autoimmune susceptibility—go unseen.
Why Are Women More Prone to Autoimmune Conditions?
Compared to men, women are up to four times more likely to develop an autoimmune disease. Numerous theories have been put forth, such as microchimerism, the X chromosome, sex hormones, environmental variables, and the microbiome. The exact cause of this autoimmune sex bias is still unknown, though.
Why Are Women More Prone to Disease?
Women are more likely than men to contract many infectious diseases, and their illness tends to progress more severely due to a variety of factors, such as biological differences, social injustices, and limiting cultural norms.
Do Women's Immune Systems Differ from Men's?
Compared to males, females are more resistant to bacterial, fungal, viral, and parasitic organisms. It is less common for females to contract microbial infections. Compared to men, females have a stronger innate immune response.
What Are the Top 5 Worst Autoimmune Diseases?
Life expectancy may be impacted by some of the worst autoimmune disease conditions.
Myocarditis autoimmune.
Sclerosis multiplex.
Lupin disease.
diabetic type 1.
vascular disease.
Myasthenia gravis.
arthritic rheumatism.
The psoriasis.
Myocarditis autoimmune.
Sclerosis multiplex.
Lupin disease.
diabetic type 1.
vascular disease.
Myasthenia gravis.
arthritic rheumatism.
The psoriasis.
Who Is More Susceptible to Autoimmune Conditions?
A study led by Stanford Medicine explains why women are more likely to develop autoimmune diseases. The reason why women are significantly more likely to develop autoimmune disorders is revealed by research: Every female cell contains a single X chromosome, which forms a molecule that can produce antibodies against a woman's own tissues.
Which Autoimmune Disease Is the Most Difficult to Diagnose?
While some common autoimmune diseases like Addison's disease, lupus, vasculitis, and other rheumatic diseases are easier to diagnose, others like Type 1 diabetes mellitus are more challenging.
Who Among the Successful Has an Autoimmune Disease?
Thank goodness for all the celebrities who have opened up about their struggles with chronic illness. Christina Applegate has multiple sclerosis, just like Blair. It is Hashimoto's disease that Gigi Hadid and Zoe Saldana had. Lupus affects Selena Gomez; Sjögren's syndrome affects Venus Williams; Graves' disease affects Missy Elliott; and fibromyalgia affects Lady Gaga.
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More information
The National Institutes of Health have more about autoimmune diseases.
SOURCE: Stanford University, news release, Feb. 1, 2024; Associated Press
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