In this study, we observed that anti-ERα Abs in the presence of E2, thus mimicking the in vivo physiological conditions of premenopausal women with SLE, were able to activate ER-dependent signaling pathways, i.e., ERK, JNK, Akt, and NF-kB, in T lymphocytes from patient with SLEDAI-2K scores ≥6 but not from those with SLEDAI-2K scores <6. The gene discussed is NFKB1; the disease is systemic lupus erythematosus.