ESR1 and systemic lupus erythematosus: Autoantibody generation and immune cell activation were drastically reduced when ERα was deleted from B cells.[47] In mouse models of SLE, ERα insufficiency significantly reduced disease severity and increased survival.[48] Liu’s findings suggested that estrogen and demethylated ERα promoter associated up-regulated ERα genes are 2 critical factors in the gender-biased development of autoimmune diseases in addition to genetic factor.[49] Lower genomic methylation levels in female SLE patients result in ER overexpression.