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SAT0397 Estrogen and Estrogens Receptors as Biomarker of Systemic Lupus Erythematosus

Background Systemic Lupus Erythematosus (SLE) affects mostly women in childbearing age, with a female:male ratio of 9:1. This gender discrepancy supports a role for estrogens and their receptors in the pathogenesis of the disease although the precise role of these hormones is not yet understood. Objectives Aim of the study was I) to evaluate ex vivo the estrogen receptor (ER) α and β expression in T lymphocytes of SLE patients and healthy subjects and their effects on T cell homeostasis; II) to investigate the humoral response against ERα and to correlate the levels of ER and anti-ERα antibodies with the clinical and serological features of SLE. Methods We enrolled consecutive female patients with SLE (diagnosed according to the 1997 ACR classification criteria) and healhty age-matched women. Pregnant and post-menopausal women and patients taking estrogens were excluded. Demographic, clinical and serological data and SLE disease activity (SLEDAI) were recorded. The expression of membrane and intracellular ER (mER and iER, respectively) were evaluated by flow cytometry in CD4+ and CD8+ T cell subsets. Anti-ERα antibodies were tested by ELISA. Estrogen-dependent cell signalling was investigated by analysing Akt, JNK, ERK, p38 and NFkB activation in T lymphocytes treated with 17β estradiol with or without anti-ERα antibodies or control human IgG. Data were expressed as mean ± standard deviation; Mann-Whitney and Pearson's correlations tests were used. A p value <0.005 was considered significant. Results We enrolled 50 SLE patients (age 34,3±7.19 years, disease duration 120,4± months) and 30 healthy females as control. The expression of mERα and iERα did not significantly differ between patients and controls in CD4+ and CD8+ T lymphocytes. Interestingly, iERβ expression in CD4+ and CD8+ T cells was significantly lower in SLE patients with active disease (SLEDAI >5) compared to those with SLEDAI <5 and to controls (p=0.023 and p=0.014; p=0.002 and p=0.0005, respectively). Anti-ERα antibodies induced ERK phosphorilation in T lymphocytes from active SLE patients (SLEDAI >5) and healthy subjects. Table 1 summarizes the correlations of ER and anti-ERα antibodies with clinical and serological features of SLE. Conclusions Results of this study show that ERα acts as an antigen in SLE; ERK phosphorilation induced by anti-ERα antibodies suggest that these antibodies may act as receptor agonist and induce proliferation of autoreactive lymphocytes. The correlation between ERα and β levels levels and skin involvement – one of the clinical features related to type I interferon (IFN) pathway – support the mutual positive regulation between ERα and IFN, already described. Finally, the different expression of ERβ accordine to disease activity suggests a role for these receptors as possible biomarkers of disease and offer new therapeutic Disclosure of Interest None declared