The Biology Behind the Autoimmunity Gender Divide
The Minerva Project • November 21, 2025
While prevalent in wider health policies and care practices, gender differences also exist within clinical science and diseases, most notably in autoimmune disease in which women constitute up to 80% of those affected.
X-chromosomes are responsible for hundreds of active protein-specifying genes, but having two copies, like in females, risks the production of those proteins. The body solves this via X-chromosome inactivation, enabled by a long non-coding RNA strand called Xist. This molecule stretches across long sections of the X-chromosome, limiting the chromosome’s expression to close to zero. However, the combinations of RNA, proteins, and DNA this creates can sometimes trigger strong immune responses. In 2015, researcher Howard Chang and his team identified almost 100 proteins that allowed Xist to bind to the chromosome, proteins that were also known to be associated with autoimmune disorders.
To eliminate other factors like hormone action, the researchers then inserted the Xist gene into a group of male mice, whilst also injecting an autoimmune disease-inducing irritant in mice both with and without the inserted gene. They found that the mice with the Xist gene developed autoimmunity, where the immune system attacks healthy cells, at a rate much higher than that of non-modified males, approaching that of females.
For decades, this process was unknown because only male cells were primarily used for research, and Xist only activates when dual copies of the X-chromosome are present. Though gender differences exist in the biology, the way we practice science and medicine should work to mitigate—not expand—those gaps. Understanding these dynamics pushes us to design research and clinical care that helps us move toward a more equitable system of healthcare.