Mice Study Suggests Previously Unknown Trigger of Autoimmune Disorders
The finding opens up opportunities for more effective, targeted treatment.
Scientists have identified a molecule — of which women have more than men — found in skin cells, high levels of which can push the immune system into overdrive, and cause it to attack the body. Researchers say this finding from experiments on mice may help explain what causes autoimmune disorders and why women are more prone to them, and could inform better treatments for those affected.
Autoimmune disorders are a group of more than 80 conditions in which one’s immune system attacks the body’s own tissue. These conditions are three times as common among women as they are in men; some autoimmune conditions, like lupus, are found almost exclusively (90%) among women. The most common autoimmune condition is rheumatoid arthritis, a long-term, progressive deterioration of joint tissue that causes pain, inflammation and immobility.
Little data exists on the prevalence of autoimmune disorders in India; doctors report an uptick in the number of diagnoses in recent years, but in a 2016 report in The Telegraph say it is difficult to determine how much that represents an actual increase, and how much that reflects greater awareness and improved access to specialized care.
To date, most theories around why autoimmune disorders are more common in women than in men rest on the extra X chromosome that women have; X chromosomes contain more immune system-related genes than any other chromosome in the human genome. Since the female sex is determined by the presence of two X chromosomes (male sex is determined by the presence of an XY pair), women have more of these immune-influencing genes at work — and hence more opportunities for things to go wrong.
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But little is known about how this influence plays out in practice. Some research suggests the biological difference in sex hormone levels might affect immunity differences in men and women. This new finding, however, offers a different explanation of the cause.
The molecule, known as VGLL3, “appears to regulate immune response genes that have been implicated as important to autoimmune diseases that are more common in women, but that don’t appear to be regulated by sex hormones,” Dr Johann Gudjonsson, PhD, who led the research team and is a professor of dermatology at the University of Michigan Medical School in the U.S., said in a statement.
Previous research by Gudjonsson’s team found women’s skin cells generally contain higher levels of VGLL3 than men’s do. In the new study, the team found that in mice, high levels of VGLL3 can affect the expression of genes that regulate immunity, switching them to trigger a self-attacking response from the immune system that causes symptoms similar to those of lupus, such as skin rashes and kidney damage. In fact, the mice produced the same antibodies — blood proteins produced and used by the immune system to neutralize threats to health — known to attack kidney tissue in human lupus patients, among other immunity malfunctions.
The researchers don’t know why women’s skin cells contain more VGLL3, nor what could prompt their levels to increase to the point of causing an autoimmune response. More research is needed, but the initial finding suggests a pathway to regulate the triggers of autoimmune disorders and develop more effective treatments.
“Many patients are frustrated that they’ve had to try multiple therapies, and still nothing is working well,” Dr Allison Billi, PhD, a resident in the dermatology department of the University’s Medical School and one of the study’s authors, said in a statement. “To be able to tell them that we’re working on a mouse that has the same disease as them, and that we need their help, brings out their motivation and interest in research. They know that it’s a long game, and they’re in for it.”
Liesl Goecker is The Swaddle's managing editor.