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A team of researchers from the Johns Hopkins University School of Medicine say they may have found the mechanism that explains the “preference” of this autoimmune condition in women
The Autoimmune Diseases they are still, to a large extent, uncharted waters for scientists, who are in a constant process of searching for the causes that cause them and the factors that aggravate them. As part of this effort, a team of researchers from the Johns Hopkins University School of Medicine claims they may have found the answer that explains the prevalence of systemic lupus erythematosus. wolf and especially in the female population. The findings were published in JCI Insight.
Systemic lupus erythematosus is an autoimmune disease that occurs in women at a rate 9 times higher than in men. A number of dysregulated genetic and biological pathways contribute to the development of lupus and its varied symptoms, which include muscle and joint pain, skin rashes, kidney problems and other complications throughout the body.
The aim of the new study was to investigate the processes taking place in the immune system of lupus patients, as well as the role of the X chromosome. The researchers discovered that there is a protein in the immune system, called receptor 7 (TLR7), which, in lupus patients, reacts to the RNA, triggering an immune response that damages healthy tissue. The study team further investigated this TLR7 immune response in lupus, specifically wanting to discover how a piece of genetic material that exists only in females, known as X-inactive specific transcript (XIST), could trigger this response. XIST is a type of RNA, which plays a key role in inactivating one of the two X chromosomes found in female cells, so as to ensure their balanced gene expression.
«Previous studies have pointed to XIST as a factor in autoimmune diseases, but more as something that could prevent autoimmune conditions like lupus, rather than causing them to developcommented study author Erika Darrah, Ph.D., assistant professor of medicine at Johns Hopkins University. «Our findings show just the opposite, that XIST increases lupus susceptibility and severity in women».
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By performing a series of cellular tests, the researchers first examined whether XIST could bind to TLR7 and initiate the receptor’s immune response. They eventually noticed that the two were closely related, with XIST triggering the production interferon, an immune protein seen at high levels in people with lupus, contributing to tissue damage. Thus, it was found that, instead of protecting against the negative effects of TLR7 and interferon in the body, XIST led to an overactive immune response, promoting the development of lupus.
«We now know that XIST has a completely different role than we thought until nowsaid study author Brendan Antiochos, MD, assistant professor of medicine at Johns Hopkins University School of Medicine. «Immune system activation through XIST and TLR7 explains why lupus is much more common in women than in men».
Wanting to further study the role of XIST in lupus, researchers looked at XIST levels in patients from two studies. The team tested blood samples from patients at the Johns Hopkins Lupus Center for XIST levels and also used publicly available data from another study, which showed levels of XIST and interferon in white blood cells taken from the kidneys of people with lupus. The experts concluded that kidney XIST levels were not only associated with higher interferon levels, but also with greater disease severity and worsening of lupus symptoms.
Dr. Darrah and Dr. Antiochos say these findings may suggest that XIST is involved in other autoimmune diseases that occur more often in women, pointing to the need for more research to explore this special process that occurs in women. Finally, the researchers claim that understanding the role of XIST in the development of lupus may pave the way for new treatments for the condition and provide an additional explanation for what causes the disease.