Published: December 13, 2019 1:22:28 pm
Researchers have discovered a potential reason for why autoimmune diseases are more prevalent in women than in men, an advance that may lead to early diagnosis and better treatment of conditions such as rheumatoid arthritis.
The researchers, including those from the University of California Los Angeles (UCLA), said autoimmune conditions affect the body’s ability to fight viruses, bacteria and infections as they cause a person’s immune cells to attack the body instead.
They said in humans, male children are born with an X and a Y chromosome, while female infants have two X chromosomes in each of their body cells.
Chromosomes are thread like coiled structures containing the genetic material Deoxyribonucleic Acid (DNA) molecules, and proteins bound to them. They carry, and transmit the hereditary unit, gene, from one generation to another.
The researchers explained that while males inherit their mother’s X chromosome and father’s Y chromosome, females inherit X chromosomes from both parents.
The study, published in the journal PNAS, showed differences in how each of the female offspring’s X chromosomes is regulated, suggesting that the X chromosome they get from their father may help to explain their misfiring immune system in the case of autoimmune diseases.
“It’s been known for many years that women are more susceptible to autoimmune diseases than men are,” said lead study author Rhonda Voskuhl, a UCLA professor.
“Figuring out why can help us develop new drugs to treat these autoimmune diseases,” Voskuhl said.
While women generally have stronger immune responses than men, with more robust responses to some vaccinations and infections, the researchers said this heightened immune system also makes women to develop autoimmune diseases.
Voskuhl said women are three times more likely than men multiple sclerosis, nine times more likely to develop lupus, and more prone to a host of other autoimmune diseases.
Voskuhl and her colleagues analysed the differences between the X chromosomes inherited from each parent, looking at the expression levels of genes in mice with the male (XY) and female (XX) chromosome set.
They identified a handful of immune system-related genes on the X chromosome which were less active, producing fewer corresponding molecules in the immune cells of female mice.
The researchers then compared mice with just one X chromosome — either a maternal or paternal X chromosome.
They determined the levels by which the chromosome had an addition of methyl chemical groups to their DNA — a process known to turn down, or block, the expression of genes.
While the methyl chemical groups aren’t part of the DNA sequence itself, the researchers said, the patterns by which these molecules are added to DNA can be passed from parent to child.
The scientists found that there was more methylation on the X chromosome inherited from the father than the one from the mother.
They confirmed that several genes on the X chromosome were less active when the X chromosome was of paternal as compared to maternal origin.
“What we’re talking about here is not mutations that affect gene sequences, but instead signals that affect how the same sequence of genes are differentially expressed in females versus males. These differences would be missed in traditional genetic studies,” Voskuhl said.
According to the researchers, the X chromosomes packaged into sperm and develops into a female offspring may have higher levels of methylation than the X chromosomes passed along in eggs from a mother to the next generation.
They said, this methylation dampens the activity levels of some immune system genes in females, making their immune activity different from those in males.
“If you can find regulators of methylation that target these differences, you might be able to reduce the immune responses of females to treat autoimmune diseases,” Voskuhl said.
“Going forward, when one considers sex as a biologic variable in diseases, it can lead to new treatment strategies,” she added.
According to the researchers, the current study is also an important step towards better understanding of sex differences in disease conditions.