New Study Reveals Lupus Condition Is Higher Among Women: Here's Why

New findings in a Johns Hopkins Medicine research for Lupus have been found, relating to the variables that cause the high incidence of the autoimmune disease in women. The research published in the Journal of Clinical Investigation Insight details the relation between the X chromosome and the immune system mechanisms.

Lupus is an autoimmune disease which affects women nine times more than males. Several dysregulated genes and biochemical pathways lead to the development of lupus and its various symptoms of muscle and joint pain, skin rashes, renal issues, and other complications throughout the body. 

The research detailed that a protein in the immune system, known as Toll-Like Receptor 7, is triggered by genetic material only found in women, known as X-inactive specific transcript (XIST). XIST is a type of RNA that plays a crucial role in inactivating one of the two X chromosomes found in female cells so that females do not have imbalanced gene expression.

Vital Findings in the Study

Erika Darrah, a former adjunct professor at Johns Hopkins Medicine, was the lead researcher of this study. She said that the findings show that XIST plays a role in promoting autoimmunity, thus increasing the susceptibility to lupus and its severity in women; this is contrary to what XIST has been implicated to earlier that it could prevent autoimmune conditions like lupus.

"XIST has now taken on a different role, an alarm signal related to autoimmunity," says study author Brendan Antiochos, assistant professor of medicine at Johns Hopkins. "The immune system activation through XIST and TLR7 is female-specific, helping explain the observation that lupus is so much more common in women compared to men."

The research team observed that XIST could strongly bind to TLR7 and trigger the production of molecules called interferons, an immune system protein seen at high levels in lupus that contributes to tissue damage in this disease. Rather than protect from TLR7 and interferon's negative effects on the body, these tests illustrated that XIST drove the process of an overactive immune response and therefore contributed to lupus development.

To further study XIST's role in lupus, researchers also examined XIST levels in patients from two lupus cohorts. The team tested blood samples from XIST levels of patients at the Johns Hopkins Lupus Center, and also used publicly available data from another study that showed the XIST and interferon levels in white blood cells taken from the kidneys of people with lupus. They assessed that not only did the levels of XIST in the kidney correlate with higher interferon levels but also, those with more XIST in their blood cells experienced greater disease severity and worsened lupus symptoms.

Researchers said that these findings may implicate XIST in other autoimmune conditions that are more often seen in women and that more research should be conducted to investigate this female-specific process, which may in turn open doors for creative therapies, as well as offer additional explanation for patients who may wonder about the origins of their disease. 

Suggested reading: Let There Be Hysteria: Why We Must Clamour For Women’s Health Research