SEX & GENDER
The Role of Sex in Autoimmune Diseases
SAEM PULSE | JANUARY-FEBRUARY 2023
By Miloni Shah on behalf of the SAEM Sex and Gender in Emergency Medicine Interest Group
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Autoimmune (AI) disease is a result of the inability of the body’s immune system to protect itself from selfantigens. Among the multiple factors that contribute, such as environmental triggers and human leukocyte antigens, the role of biological sex is crucial in the development of autoimmunity. Females have a more robust immune system than males in both humoral and cellular immunity. Additionally, sex hormones influence the propensity of AI conditions, with estrogen and progesterone stimulating immune effects and androgens largely suppressing them through autoimmune regulator (AIRE) expression that prevents autoreactive T cells. For this reason, females are more at risk of developing AI conditions, and currently, 80% of
“...it is vital to understand the current therapies used to treat both acute and chronic manifestations of AI conditions and whether these treatments have been studied based on sex differences.” individuals with AI diseases are female. Sex chromosomes also play a large role in the sex bias of autoimmunity, as the X chromosome contains many immune-related genes, including CD40 ligand, tyrosine-protein kinase BTK,
and chemokine CXCR3, among others. Lastly, immunity in the gut microbiota is influenced in a sex-specific manner, as seen by many animal models for type 1 diabetes, where male microbiota seems to play a protective role.