Improper X Chromosome Inactivation and Hormonal Fluctuations Linked to Autoimmunity

Approximately 80% of autoimmune disease patients are women. A review article titled The Prevalence of Autoimmune Disorders in Women: A Narrative Review explores several possible reasons why women are more susceptible than men to autoimmune diseases including:

• Improper X chromosome inactivation: During embryonic development, one of the two X chromosomes in women becomes inactivated to prevent overexpression of genes. If X inactivation doesn’t occur properly, it can lead to the overexpression of immune-associated genes. This is a hypothesis behind why eight out of every nine people with systemic lupus erythematosus are women.
• Hormonal changes: It’s possible that rheumatoid arthritis, Sjogren’s syndrome, and psoriasis occur more in women because they typically experience more hormonal changes than men. Estrogen, which can decrease inflammation, is thought to protect against rheumatoid arthritis and Sjogren’s syndrome. These two diseases have been associated with decreased estrogen levels during menopause. Hormonal changes during pregnancy and puberty have also been linked to autoimmune disease onset.

Citation:

Angum, F., Khan, T., Kaler, J., Siddiqui, L., & Hussain, A. (2020). The prevalence of autoimmune disorders in women: A narrative review. Cureus. https://doi.org/10.7759/cureus.8094