Sex Bias in Autoimmunity: New Findings and New Opportunities

Autoimmune diseases result from the immune system's inability to discriminate between self and foreign antigens, leading to development of self-reactive immune cells and autoantibodies that can cause organ damage and failure. It has long been known that many autoimmune diseases are more common in females. Although much progress has been made over the years, the exact mechanisms for this sex bias are not yet fully understood. In this review, we provide an overview and update on how chromosomes, genes, sex hormones (including gender-affirming hormone therapy), immunometabolism, and the skin can play a role in sex-biased autoimmunity. We also identify gaps in our understanding that require additional research. In an era of increased development of personalized medicine, a thorough understanding of sex bias in autoimmunity may facilitate the development of much-needed targeted therapeutics, thereby reducing the risks of broader immunosuppression and adverse effects that lead to premature termination of treatment by patients.