United States: When out of balance, the immune system attacks the very bodies it’s supposed to defend: this condition is called autoimmune disease, and women are far more likely to get it. Finally, new knowledge on why this happens may be revealed in the latest study.
The X Chromosome Factor
On Thursday, Standford University investigators said that it just has to do with how the body copes with the extra X chromosome in females. This investigation could pave the path for better methods of delivering what are not simple illnesses to identify and treat.
“This transforms the way we think about this whole process of autoimmunity, especially the male-female bias,” said University of Pennsylvania immunologist E-John Wherry, who wasn’t involved in the study.
Some researchers estimated that autoimmune disorders comprise up to 24 million citizens, but authorities suggested as many as 50 million Americans irrespective of their gender, all ages, and race – may carry one of over a dozen illnesses, including lupus, rheumatoid arthritis, or multiple sclerosis app. Throughout their pursuit of discovering this flaw, for over five decades, scientists have been unwaveringly surprised by the fact that 4 out of every five patients are women.
One logical explanation for this could be the X chromosome. For one, females have two X chromosomes, while males have a combination of one X and Y.
Further research, which appeared in the Cell Journal, confirmed that there was another thing about extra X, but this one came up as a surprise.
In each of the cells, there are 23 pairs of chromosomes that contain our DNA (also the final pair of chromosomes, which dictates natural gender).
There are hundreds of genes in the X chromosome, and this is more than what males have so far as the Y chromosome, which lacks or contains fewer genes. To ensure that cells are not infested with excess goodies, the X chromosome genes should either inactivate each other so one copy of this chromosome is switched off, or the cells will behave like some three-lettered words (talk about intoxication).
Xist RNA’s Role
Xist — short for the so-called inactivation of the X chromosome — is a unique type of RNA that settles on specific locations along the second, extra X chromosome present in cells and attracts proteins that fortify it with dense patches attached. In this way, it shuts down an otherwise functioning copy of an entire chromosome without affecting another special.
Dr. Howard Chang, a Stanford dermatologist, enquired what Xist was up to in his lab to find close to 100 of these proteins glued on by the activity of their own mechanisms. Chang identified most as related to types of autoimmune disorders affecting the skin – patients can have “autoantibodies” that incorrectly target these normal proteins.
“That got us thinking: These are the known ones. What about the other proteins in Xist?” Chang said. Maybe this molecule, found only in women, “could somehow organize proteins in such a way as to activate the immune system.”
However, it is true that Xist alone does not cause autoimmune events, nor do women live as such. The mainstream idea for a good while has been that susceptibility to immune dysregulation requires an additive interaction between genetic makeup and an environmental trigger, point mutation alone not being enough.
Mice Model Experiment
Chang’s team then decided to construct male lab mice to produce Xist –control of inhibiting a single X chromosome. They watched out for the consequences later on, and this was done.
Additionally, scientists developed mice specifically that might develop a lupus-like illness that could be brought on by a chemical irritant.
It was observed that Xist-producing mice gave rise to specific hallmark-signal protein aggregates, which induced lupus-like autoimmunity when challenged at almost female levels — consistent with the fertility-blocking effect of primordial germ cell failure.
“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,” explained Chang, who also supports The Associated Press Health and Science Department.
Implications for Future Treatment
Besides mice, investigators also analyzed blood sera from 100 patients and identified unprecedented autoantibodies to the Xist-associated proteins, which were not known as markers of autoimmune disorders. A potential reason, Chang suggests, is that the autoimmunity tests that were standardly used had cells of male males.
A lot more studies are needed, but the results “could lead us to a quicker way, so we don’t even have to test for all the things we do or measure in people who look clinically and immunologically completely different,” suggested Wherry from Penn.
“You may have autoantibodies to Protein A, and another patient may have autoantibodies to Proteins C and D,” but knowing they’re all part of the larger Xist complex allows doctors to better hunt disease patterns, he added. “Now we have at least one big part of the puzzle of biological context.”
Stanford’s Chang wonders if it may even be possible to interrupt the process one day.
“How does that go from RNA to abnormal cells? This will be the next step of the investigation.”