Dermatology Xagena

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Master regulator in genes may make women more susceptible to autoimmune diseases

Women represent nearly 8 out of every 10 people with autoimmune diseases. Although the hugely disproportionate statistics are well known, the scientific community is still trying to figure out why women's immune systems are more likely to become overactive and attack their own healthy cells.

Researchers at the University of Michigan released a study in Nature Immunology that explores why women are more often afflicted with autoimmune diseases. The paper propels their research, and eventual goal of finding successful treatment, in a different direction from existing work on sex hormones.

Researchers have identified a gene expression difference between the sexes that is associated with susceptibility to autoimmune disease.

Autoimmune diseases take many forms across the body, from psoriasis patches on the skin to lupus throughout the body to rheumatoid arthritis in the joints, yet all conditions affect women at a higher rate. It often takes years to get a correct diagnosis for these chronic diseases. There are no cures for the estimated 7.5% of people in the U.S. dealing with them, and current treatments come with devastating side effects.

It's important to examine changes to the skin in diagnosis and treatment of autoimmune disease. For example, four of 11 criteria for a lupus diagnosis relate to the skin, with features like rashes.

The researchers decided to take a broader approach with this study, investigating gene expression in the skin of healthy subjects, including skin biopsy samples from 31 females and 51 males.

Some striking differences in gene expression between the women and men were found. In total, 661 genes were expressed differently between the sexes.
Many of those genes had immune function, and overlapped with genetic pathways and risk genes that related to autoimmune diseases.

Following that finding, researchers were able to identify VGLL3, a master regulator of the female-biased immune network.
This inflammatory pathway promotes autoimmunity in women. VGLL3 was also active in men with autoimmune diseases.

Much of the existing work on gender differences in autoimmune diseases focuses on sex hormones, investigating the effects of hormones on women's immune systems to explain the disparity.

However, the novel inflammatory pathway, VGLL3, is not hormonally regulated.

Researchers found no evidence of involvement of estrogen or testosterone in the immune differences between women and men. ( Xagena )

Source: University of Michigan, 2016