Why Women Are More Prone to Autoimmune Diseases

An estimated 75% of people with autoimmune diseases are female, according to the American Autoimmune Related Diseases Association. In the case of lupus, the gender difference is even more severe, as nine out of 10 of those afflicted are women.

What’s more, autoimmune diseases are among the leading causes of death and disability in girls and women 65 years of age and younger.

Asa Tivesten, MD, professor of medicine at Sahlgrenska Academy, Sweden, was part of a team of researchers who recently explored why women are more susceptible to these diseases, hoping to provide better treatment for the diseases in the future.

“We know testosterone reduces the number of B cells, a type of lymphocyte that releases harmful antibodies,” she says. “Our scientific question was we wanted to find out what the mechanism behind testosterone to the relation of the number of B cells in the spleen was. We wanted to understand what the connection actually looks like, mechanisms that have so far been unknown.”

The study, published in Nature Communications, provided findings on possible mechanisms behind gender differences in the occurrence of rheumatism and other autoimmune diseases.

Read: How Using DNA Banks Can Improve Autoimmune Disease Treatment

Tivesten and her research team began studying mice, as there are cell-specific knockouts and castration experiments where you take away the testes and thereby take away the testosterone production of the mouse. It next confirmed its results in a cohort of healthy men, studying blood samples from 128 males.

“We looked at the testosterone levels in these men and we defined a subpopulation of them as having low testosterone levels and we saw that those men with low testosterone levels had higher BAFF levels,” Tivesten says.

The data revealed that if you eliminate testosterone, you get more BAFF and thereby more B cells in the spleen because they survive to a greater extent. This recognition of a link between testosterone and BAFF is something that hasn’t been known before.

“What we have found is a physiological regulation, a hormone regulates an important factor in the immune system and that is actually physiology,” Tivesten says. “But the finding has implications for pathophysiology, we think, because BAFF is so tightly coupled to development of autoimmune disorders and especially SLE.”

BAFF inhibitors is the first drug that has become registered for SLE in more than 30 years, which Tivesten notes is an extremely long time without any new medications for this very serious disease. And yet in her clinic, these BAFF inhibitors have been a little bit of a disappointment and haven’t lived up to expectations.

“So, there has been a question of how well is BAFF coupled to autoimmune pathophysiology?” she says. “There was a very important paper in the New England Journal of Medicine last summer where they looked at genetic variations in the BAFF gene and they could see that people with genetic variants that resulted in higher BAFF levels are more prone to develop SLE and multiple sclerosis. I think those were the major diseases that could be coupled to BAFF.”

Additionally, the findings compare closely to a previous study showing that genetic variations in BAFF could be connected to the risk of diseases such as lupus.

“That’s why understanding how the body regulates the levels of BAFF is so important, so we’re able to continue to put the pieces together and try to understand which patients should have BAFF inhibitors and which should not,” Tivesten says. “Our study serves as a basis for further research on how the medicine can be used in a better way. I think this information is important for those that treat and form and design clinical studies with BAFF inhibitors and it will be interesting to see if the findings will lead to any new study schemes or stratifications of patients.”

Keith Loria is an award-winning journalist who has been writing for major newspapers and magazines for close to 20 years, on topics as diverse as sports, business, and healthcare.