Mechanisms underlying sex differences in autoimmunity

• Published in: The Journal of clinical investigation 2024-09, Vol.134 (18), p.1-10
• Main Authors: Fairweather, DeLisa, Beetler, Danielle J, McCabe, Elizabeth J, Lieberman, Scott M
• Format: Article
• Language: English
• Subjects: Androgens; Animal experimentation; Animal models; Animals; Antibodies; Antigens; Autoantibodies; Autoantibodies - immunology; Autoimmune diseases; Autoimmune Diseases - genetics; Autoimmune Diseases - immunology; Autoimmunity; B cells; Cell culture; Chromosomes, Human, X - genetics; Chromosomes, Human, X - immunology; Cisgender; Demographic aspects; Development and progression; Disease; Diseases; Drug development; Environmental law; Epigenesis, Genetic; Epigenetic inheritance; Epigenetics; Estrogen; Estrogens; Female; Females; Gender differences; Gene regulation; Genes; Genetic aspects; Gonadal Steroid Hormones - immunology; Gonadal Steroid Hormones - metabolism; Haplotypes; Health aspects; Hormones; Hormones, Sex; Humans; Immunity (Disease); Immunosuppressive agents; Influenza; Lymphocytes; Male; Males; Medical research; Medicine, Experimental; MicroRNAs - genetics; MicroRNAs - immunology; MicroRNAs - metabolism; miRNA; Mitochondria - genetics; Mitochondria - immunology; Mitochondria - metabolism; mRNA; Pathogenesis; Pathogens; Physiological aspects; Review Series; RNA; RNA viruses; Sex Characteristics; Sex differences; Sex hormones; Thymus gland; Toxins; Vaccines; Womens health
• ISSN: 0021-9738; 1558-8238; 1558-8238
• DOI: 10.1172/JCI180076

Autoimmune diseases are a leading cause of disability worldwide. Most autoimmune diseases occur more often in women than men, with rheumatic autoimmune diseases being among those most highly expressed in women. Several key factors, identified mainly in animal models and cell culture experiments, are important in increasing autoimmune disease in females. These include sex hormones, immune genes including those found on the X chromosome, sex-specific epigenetic effects on genes by estrogen and the environment, and regulation of genes and messenger RNA by microRNAs found in extracellular vesicles. Evidence is also emerging that viruses as well as drugs or toxins that damage mitochondria may contribute to increased levels of autoantibodies against nuclear and mitochondrial antigens, which are common in many autoimmune diseases. The purpose of this Review is to summarize our current understanding of mechanisms that may determine sex differences in autoimmune disease.