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Thread: Why women get autoimmune diseases in greater numbers than men....from The Atlantic

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    Distinguished Community Member Lazarus's Avatar
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    Default Why women get autoimmune diseases in greater numbers than men....from The Atlantic

    A Breakthrough in the Mystery of Why Women Get So Many Autoimmune Diseases
    Evolution might have played a trick on women’s immune systems.

    OLGA KHAZAN
    10:40 AM ET
    An illustration of a placenta
    ILBUSCA / GETTY
    About 65 million years ago, shortly after the time of the dinosaurs, a new critter popped up on the evolutionary scene. This “scampering animal,” as researchers described it, was likely small, ate bugs, and had a furry tail. It looked, according to artistic renderings, like an especially aggressive New York City rat. And it had a placenta, an organ that grows deep into the maternal body in order to nourish the fetus during pregnancy.


    The rodentlike thing would become the common ancestor of the world’s placental mammals, with descendants that include whales, bats, dogs, and humans, among many other species. And today, the placenta might hold the key to one of the most enduring mysteries in human medicine: Why do women suffer much higher rates of autoimmune disease than men do?

    Autoimmune diseases turn people’s own immune systems against their bodies. In the United States alone, women represent 80 percent of all cases of autoimmune disease. Women are 16 times more likely than men to get Sjogren’s syndrome, in which the immune system goes after the glands that make tears and saliva, and nine times more likely to have Hashimoto’s thyroiditis, in which it sets its sights on the thyroid. Sjogren’s forced Venus Williams to drop out of the U.S. Open in 2011. The singer Selena Gomez underwent a kidney transplant after suffering complications from lupus, which is eight times more common in women than in men



    Some scientists now think the placenta itself might be the reason why women are so disproportionately affected. In a paper published last week in the journal Trends in Genetics, Melissa Wilson, an evolutionary biologist, along with her colleagues from Arizona State University, put forward an explanation called the “pregnancy-compensation hypothesis.” It suggests that women’s immune systems are engaged in a fierce tug of war with placentas, even when the organs aren’t actually present.

    Here’s how the theory goes: Women—and all other placental mammals—evolved such that they would be pregnant for many of their adult years. Before the advent of birth control, that was pretty much the fate of the female sex. In modern hunter-gatherer populations, Wilson told me, women typically have eight to 12 children each.

    Though bearing so many babies might sound grueling, women’s bodies evolved to cope. When the placenta grows during pregnancy, the organ sends signals to the mother’s immune system to change its activity so that the mother’s body doesn’t eject the placenta and the fetus. This might even mean turning down the immune system in some ways, or for some periods of time. Turning down the immune system too much, though, risks leaving women sensitive to pathogens, which would also be bad for the fetus. So instead the mother’s immune system ramps up in other ways throughout adulthood, Wilson and her colleagues think, so as to remain vigilant against germs even when some of its parts become dormant during pregnancies.

    Things get complicated, however, when those pregnancies don’t actually occur. Women today tend to have far fewer children—fewer than two on average in the United States, according to the CDC. Wilson reasons that without a more or less constant pushback from placentas during pregnancies—the pushback that women’s immune systems have evolved to anticipate—the immune system can get too aggressive, too ramped up. It starts looking for things to attack that aren’t dangerous, which is how autoimmune diseases set in.

    For millions of years, minus the past 100, “the immune system was expecting to have exposure to a placenta,” Wilson says. Imagine if you’re pulling on something heavy, and then the rope snaps. “If you suddenly don’t have that heavy thing anymore,” she says, “you’re gonna go off the moon.”

    This is certainly not the first theory for why women suffer from more autoimmune disease than men do. One has to do with a protein called BAFF; another has to do with the fact that women have two X chromosomes instead of one. The way Wilson sees it, the pregnancy-compensation hypothesis synthesizes many of the previous theories into one and provides the evolutionary explanation behind them. “They were all right,” she says. “But everyone was looking under their own streetlight, and we just waited for it to be daytime.”

    Wilson says that so far, no one has come forward to attack her for being wrong, despite the seeming boldness of this theory. Several experts I spoke with—even those who have competing theories for the sex difference in autoimmune disease—say Wilson’s theory might fit with what we already know. “I would say there’s not one theory that explains all [autoimmune diseases],” says Nikolaos Patsopoulos, an assistant professor of neurology at Brigham and Women’s Hospital. “This isn’t Lord of the Rings.” Still, he says, “this theory puts together a lot of things we know that are true and some that we’re still trying to understand.”

    Johann E. Gudjonsson, a professor of skin molecular immunology at the University of Michigan, found that women have more of a molecular switch called VGLL3 in their skin than men do, and that all this VGLL3 might be what causes a heightened immune response in women. In this case, then, the VGLL3 might be how the body ramps up the immune system, but the pregnancy-compensation hypothesis might be why it does so.

    Similarly, Hal Scofield, a professor of pathology and medicine at the University of Oklahoma, says that it appears there are lots of genes involved in the immune response on the X chromosome, and because women have two X chromosomes while men have only one, women have more of those immune genes. The placental theory that Wilson’s team devised could be the reason this happens. Because women have to have strong immune systems that buck against the placenta, they evolved to produce more genes involved in the immune response. “I don’t think there’s any way out of thinking that placental pregnancy has to have influenced the evolutionary immune system,” Scofield told me.

    Not everyone I reached was impressed by the paper. David Hafler, a professor of neurology at the Yale School of Medicine, told me, “Ideas are cheap. It’s data which is hard to get.” In other words, sure, the pregnancy-compensation hypothesis is an interesting idea, but it still has to be tested.

    Wilson says there are opportunities to do just that. Scientists could try to determine whether the number of pregnancies a woman has is predictive of her risk of autoimmune disease. If Wilson’s theory holds, women who have more pregnancies should have a lower risk. Or scientists could study the differences between mammals in the wild and zoo animals, which are sometimes on birth control, to determine whether they have differences in their autoimmune function.

    Some people might take Wilson’s findings to mean that women should simply be pregnant all the time, but that’s far from the takeaway here. Pregnancy, after all, also carries major health risks, and not all women want to have 12 kids. And Wilson’s findings suggest that women’s extra-strong immune systems might protect them in some cases. Women are less likely than men to get certain kinds of nonreproductive cancers, for example.

    Wilson says that the hope is to eventually learn what it is in the immune system that’s trying to respond to the placenta, and to target that thing with vaccines or treatments. More research could mean major improvements in the way women’s autoimmune diseases are treated. “I’ve never been more excited about an idea than I am about this,” Wilson told me. “This is the first time that I can see my work having a direct impact in the next 10 years on human health.”

    We want to hear what you think about this article. Submit a letter to the editor or write to letters@theatlantic.com.

    OLGA KHAZAN is a staff writer at The Atlantic.
    Last edited by Lazarus; 06-18-2019 at 04:02 PM.
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    Thanks for sharing! I am always interested in all aspects of how pregnancy effects women and fetuses and this would make sense. The fetus has separate DNA so the mother's body has to take extra steps not to reject the fetus the way it would a foreign body. Some studies I read years ago mentioned that miscarriage could be caused by the mother's immune system rejecting the fetus. I'v also seen some articles saying if a vaccine(I'm for vaccines) is given at the wrong time it could trigger autoimmune disease like diabetes type 1. I wonder if there are any studies on having vaccines during pregnancy recently...
    Last edited by funnylegs4; 06-18-2019 at 09:08 PM.
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    And I wonder if there are any studies exploring whether women with a larger number of children are less apt to have MS than childless women or women with only a couple of children.
    MS diagnosed 1980. Avonex 2002-2005. Copaxone 6/07 - 5/10.
    Member of this MS board since 2001.

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    I donít know. Good that the researcher is thinking about this. But, it just doesnt seem correct. The Yale prof of Neurology echoes my sentiment.

    Other things come along with women of few or no children. Lack of intense busyness in family life puts them more in the outside the family world, where they are exposed to more pathogens, for example. Or more stresses of the kind that arent affiliated with raising children....

    Collecting data to prove or disprove this hypothesis of the author, can , though , be fruitful. While doing the research, other findings might come to light that create new ideas on why women get these diseases more often.

    And how about all the female children who develop autoimmune disorders?

    Or perhaps its because males tend to get down and dirty in childhood, more often than females,conferring some type of immunity to these autoimmune disorderó talk is cheap. Data are hard to come by.

    Having placentas is only one factor that differentiate females from males.

    Do Nuns have more autoimmune disorders than non-Nuns?

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    Quote Originally Posted by agate View Post
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    And I wonder if there are any studies exploring whether women with a larger number of children are less apt to have MS than childless women or women with only a couple of children.
    It is an interesting vein of investigation.
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    Quote Originally Posted by funnylegs4 View Post
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    Thanks for sharing! I am always interested in all aspects of how pregnancy effects women and fetuses and this would make sense. The fetus has separate DNA so the mother's body has to take extra steps not to reject the fetus the way it would a foreign body. Some studies I read years ago mentioned that miscarriage could be caused by the mother's immune system rejecting the fetus. I'v also seen some articles saying if a vaccine(I'm for vaccines) is given at the wrong time it could trigger autoimmune disease like diabetes type 1. I wonder if there are any studies on having vaccines during pregnancy recently...
    The pregnancy and estrogen issue has always attracted my reading attention.
    I too like it when a researcher looks at a seemingly obvious situation (more MSers are women) and asks why.
    Linda~~~~

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    But then there's Howie. Has anyone seen my placenta? It seems to be missing.
    Evolution spans the Universe.

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    When I began to have more and more symptoms there were several factors that came into play. The estrogen thing was one of them. I had been on 1.25mg of Premarin since in my 30s due to early hysterectomy. My PCP cut me back to .625mg all at once. So I was getting 1/2 the amount of estrogen all of a sudden. I know it was not a great deal of time before my MS became very active, though I did not know at the time it was MS. But it was after that sudden drop that I began to have problems with walking more often. I remember stumbling and trying to blame it on my shoes. I remember trying to walk in a hurry down a hall at work and while looking down at some papers I veered off to the left, my bad side, and walked into a wall, and on and on. Any correlation? I certainly don't know, but I do know I wish my PCP had left that part of my treatment up to my Gyn because he would have kept me on the 1.25mg.

    Anything that comes up about estrogen, like Linda, I sit tall and pay attention.

    After my diagnosis I attended a Newly Diagnosed Seminar. It was presented by a lady who was like Cherie. She had MS and was a Nurse, she spoke for the MS Society, also at live research programs, she attended many things that were put on by professionals across the country and went on some of the cruises. She is my age and told me that she had had a hard time early on, but then in about her 50s was put on estrogen and she said it was after that that she began to get better. She was doing very well the last time I spoke with her. That has been quite awhile. The only other thing she did was exercise. When she was diagnosed there were no DMTs and she watched her diet and exercised, but periodically had pretty bad spells. She did not know if the estrogen had anything to do with it or not, but told me she hoped they never took her off it.
    Virginia

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    Thats interesting Virginia! I wish I could recall when I stopped estrogen, whether it was right before my first MS attack.

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