Our results suggest that the imbalance in the expression of ER subtypes, i.e., the low expression of the anti-inflammatory ERβ and the consequent predominance of ERα signaling, in T cells from female patients with active SLE may impact lymphocyte sensitivity to E2 and to anti-ERα Ab stimulation, interfering with cell signaling and contributing to inflammation and disease activity. Here, ESR2 is linked to systemic lupus erythematosus.