Did Researchers Finally Discover Why Multiple Sclerosis is More Common in Women?

Women are more likely to develop autoimmune diseases like multiple sclerosis (MS), and a lab accident has come closer to determining the reasoning behind this, according to findings published in The Journal of Immunology.

Researchers from Northwestern University accidentally used all female mice instead of all male mice in an experiment which lead to the discovery that the innate lymphoid cell, a type of white blood cell, exhibits different immune activities in males versus females. A mouse model of MS was induced into the animals and essentially 100% of the mice got sick if they were female. However, a notable difference the researchers found was that male mice either do not get sick or experience lesser symptoms. That’s the reason behind typically using all female mice in studies of autoimmune diseases.

“Women are three to four times more likely than men to develop MS, and much of the current research focuses on the question, ‘Why do females get worse disease?’” lead author Melissa Brown, PhD, explained in a press release. “Now, thanks to a serendipitous moment in the laboratory, we are approaching this research from the opposite way, asking, ‘Why are males protected from disease?’”

In the original study, it was planned that two groups of female mice were going to be observed. The first group was normal while the other group had a genetic mutation in a growth factor receptor called c-kit, which prevented the development of specific immune cells. In prior experiments similar to this study, the female mice with the mutation did not get as sick as the normal mice. Instead of using females for this study, however, male mice were used.

“It was an honest mistake, but the results were striking; the male mice with the mutation got very, very sick,” Brown said. “Because this strain of male mice never get very sick, I thought there was some sort of mistake, so I asked the student to repeat the experiment.”

In the repeated experiment, the results were duplicated. The mice with the c-kit mutation lacked type 2 innate lymphoid cells, typically present in bone marrow, lymph nodes, and thymuses of both males and females. The researchers hypothesized that male mice produced a protein that could have protected them from the disease in a way that interfered with the inflammatory immune response.

Using this information, future studies can further uncover why males are more protected and develop methods that block diseases in females.

“The hope is to target these cells in a sex specific way and provide a therapy with fewer side effects,” Brown concluded. “This early research may have implications for understanding other diseases such as lupus and rheumatoid arthritis, which also show a female bias.”