Sex and autoimmune disease: Four mechanisms pointing at women

The ultimate goal of modern medicine is a personalized approach being tailored on the single patient, ie, tailored, based on a finely tuned definition of the immunogenetics, epigenetics, microbiome, and biomarkers, to maximize results and minimize risks particularly of new targeted treatments. Among individual factors around which to tailor the patient management are sex and age, with gender-medicine finally becoming central to the research agenda. Of note, we are not convinced that a whole personalized medicine approach in its current form will necessarily include gender medicine and thus this should remain central to the research agenda. To tackle this crucial issue, however, we should first be able to answer a question of paramount importance, that is, why does autoimmunity affect women more than men? The growing number of experimental works in this area militate against an easy answer to this question, but we will herein briefly discuss four major candidates (sex hormones, sex chromosomes, environmental factors, and the microbiome) to which some unsuspected others may be ancillary.