Sex/Gender Differences in Rheumatic Diseases: A Focus on Lupus and Rheumatoid Arthritis

Rheumatic diseases are much more common among women than men, suggesting that the X chromosome and sex hormones are actively involved in the sex difference of the diseases. In particular, X chromosome inactivation is one of the key determinants of sex difference in rheumatic diseases, causing a different gene-dose effect between the two sexes. Another important mechanism is microRNAs (miRNAs), 10% of which are residing in the X chromosome, while a few are found in Y. These small noncoding RNAs regulate the translation of a specific gene and many of X-chromosome-residing miRNAs are related to immune genes. The third factor contributing to the sex difference in rheumatic diseases is sex hormones. In general, testosterones negatively regulate immune response, while estrogens reinforce it. In addition, estrogens can activate or inhibit miRNA related to immune functions, further contributing to the sex difference of rheumatic diseases. This chapter will present how these mechanisms work in rheumatic diseases by taking examples of systemic lupus erythematosus and rheumatoid arthritis.