Sex and autoimmunity: proposed mechanisms of disease onset and severity

Introduction: Chronic autoimmune diseases affect 5–10% of the population worldwide and are largely predominant in women. Sex hormone changes have been widely investigated based on changes in the clinical phenotypes observed during pregnancy and menopause.

It is known that females with autoimmune diseases manifest a higher rate of circulating leukocytes with a single X chromosome, and there have been several reports on the role of X chromosome gene dosage through inactivation or duplication in autoimmunity. However, it is also important not to overlook men with autoimmune diseases, who might manifest a more frequent loss of the Y chromosome in circulating leukocytes.

Areas covered: In the present review, we will discuss the current evidence supporting the mechanisms of female predominance in rheumatic diseases, by discussing the role of reproductive history, sex hormones and abnormalities related to them, clinical differences between male and female patients, and epigenetic changes that have been evaluated through twin studies on genetic and environmental changes in rheumatic patients.

Expert opinion: The influence of sex hormones and chromosomes on the function of the innate and adaptive immune systems needs to be clarified, to better understand the risk of autoimmune diseases, early diagnostic tools, and therapeutic response.