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Why are women more likely to develop autoimmune diseases such as multiple sclerosis? Lupus And rheumatoid arthritis is a long-standing medical mystery, and a team of researchers at Stanford University may now be one step closer to solving the problem.
How the female body handles the extra X chromosome (males only have one Y chromosome) may help explain why women are more susceptible to these diseases, new research suggests. Primarily chronic conditions involve the extracellular immune system attacking its own cells and tissues.
While the research in mice is preliminary, the observations could help inform new treatments and ways to diagnose the disease after further study, said Dr. Howard Chang Sr. Author of a paper published in Cell Journal On February 1.
Chang, a professor of dermatology and genetics at Stanford School of Medicine, was interested in the topic because the symptoms of some autoimmune diseases, such as lupus and scleroderma, manifest as rashes on the skin.
“A lot of the diseases we see in our clinics, especially immune-related diseases, show this really female bias. And I’ve always thought about this from my own clinical practice,” he said.
About 24 million people in the United States have more than 80 autoimmune diseases. The illness occurs when a person’s immune system becomes confused and begins to react as if it has an infection when none is present, explained Montserrat Angera, an associate professor in the Department of Biomedical Sciences at the University of Pennsylvania School of Veterinary Medicine.
They are the same players (those) who react to the virus or bacteria. They are in the immune system, but in autoimmune disease the ‘infection’ is not being cleared, it persists and persists, strengthens and damages the tissues, as in autoimmune disease,” Angurera, who was not involved in this. The study explained. “Some of them affect the whole body and Others are localized to a specific body.”
Other researchers focused on the “female bias” of the diseases by analyzing sex hormones or chromosome counts. Chang instead determined the role played by a molecule called Xist (pronounced as Xist), which is absent in male cells.
The main function of the Xist molecule is to inactivate the second female X chromosome in embryos, preventing the body’s cells from acquiring a potentially toxic double whammy of the chromosomal protein-coding genes.
“Xist is a very long RNA, 17,000 nucleotides or letters long, and it binds to about 100 proteins,” Chang said. Xist molecules work with those proteins to shut down gene expression in the second X chromosome.
Ten years ago, while studying for the exam to renew his medical license, Chang made a connection. He observed that many of the proteins that bind and silence the X chromosome are associated with skin-associated pathogens.
Chang hypothesized that a cluster of protein molecules formed when Xist binds to the X chromosome is the cause of autoimmune disease.
To investigate, Chang decided to study how it, which is naturally produced only by female cells, would work in male mice – something made possible by genetic engineering. This would be the first step to rule out competing explanations for women’s susceptibility to autoimmune disease, such as sex hormones or proteins made on the second X chromosome not being completely lost, he said.
When mice engineered to have the gene that produces Xist were injected with a lupus-like chemical irritant, the team found that the male mice developed autoantibodies. – At a faster rate in female mice, it shows that Xist-binding proteins can trigger an immune response. The experiments were not designed to show whether Xist or related proteins caused autoimmune disease in animals.
Chang and his colleagues analyzed blood serum samples from people with lupus, dermatomyositis and systemic sclerosis and compared them to samples from people without the autoimmune disease. The samples from patients with autoimmune diseases produced high levels of autoantibodies in response to Xist-related proteins, the researchers said.
Overall, the data point to a “significant role” for Xist in explaining why autoimmune disease affects women.
The research shows that the inactive X chromosome machinery is important and may play a role in autoimmune disease in women, Montserrat said.
But the latest discovery, she added, could be just one piece of a much larger puzzle — a “coral reef” in a larger ocean. It’s not clear whether the proteins associated with Xist are actually causing disease, she said. In addition, environmental factors play an important role in autoimmune disease.
“It’s not just an individual’s genetics…there’s a whole other aspect, which is the interaction with the environment,” Angera said. “So these are diets, MicrobiomeThen behaviors like smoking.
Read more: Lab rats are overwhelmingly male, and that’s a problem.
Autoimmune diseases are difficult to diagnose and take a long time to diagnose. Ultimately, Chang said, he hopes the findings can speed up that process.
“I think the potential of the probe[of Xist and IF]is there to track and explore,” Chang said. “The second area we are most interested in is therapeutics. Now that we know Xist is an important driver, how can we stop this process?”