Differential expression of estrogen receptors in women with systemic lupus erythematosus.

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease primarily affecting women. T cell activation markers (calcineurin, CD154) increase in SLE T cells cultured with estradiol 17-beta. Biological effects of estradiol are mediated through 2 receptor proteins, estrogen receptor-alpha (ER-alpha) and estrogen receptor-beta (ER-beta). We compared the amount of estrogen receptor subtypes in T cells and measured the ability of receptor agonist-specific ligands to activate marker gene expression. T cells were isolated from 22 female patients with SLE and 17 control women. The amount of ER subtypes was measured by immunoblotting. Some T cells were cultured with ER-alpha or ER-beta-specific agonists. Receptor activation was measured by increased expression of the T cell activation markers CD154 and calcineurin. Although the amount of ER-alpha appeared to be less in SLE T cells than in control T cells, the difference was not statistically significant (p = 0.081). The quantity of ER-beta was similar in SLE and control T cells. The expression of ER-alpha or ER-beta was independent of menstrual cycle phase, age, or SLE disease activity. Calcineurin and CD154 expression increased in SLE T cells cultured in medium containing ER-alpha and ER-beta agonists. These data indicate that both ER subtypes activate calcineurin and CD154 in SLE but not in normal T cells. Variation in the amount of ER-alpha in SLE T cells suggests this receptor subtype participates in the sensitivity of SLE T cells to estrogen.