POS1407 UNBALANCED LEVELS OF CIRCULATING NEUROACTIVE STEROIDS IN NEUROPSYCHIATRIC SYSTEMIC LUPUS ERYTHEMATOSUS: A PILOT STUDY FOR AN UNEXPLORED SCENARIO

Background Sex hormones have effects on the development, progression and severity of SLE, prevalently affecting women (F:M=9:1). The neuroprotective, neurotrophic anti-inflammatory properties a class progesterone-derived NeuroActive Steroids (NASs), prompted numerous investigations about potential these GABAA receptor allosteric modulators. However, no data NASs neuropsychiatric SLE (NPSLE) are available. Objectives This exploratory pilot study aims to delve into new unexplored landscape by assessing circulating levels in NPSLE patients. Methods A cohort 16 patients without NP manifestations with onset diffuse symptoms was enrolled. Mood disorders cognitive dysfunction were defined according Center for Epidemiologic Studies Depression Scale (CES-D) battery neuropsychological tests, respectively, interpreted neuropsychologist. group 8 healthy controls (HCs) matched mean age gender ratio also recruited. Exclusion criteria: ongoing contraceptive or hormonal treatment; glucocorticoid pulse treatment variations 6-month before blood collection; anxiolitic, anticonvulsivant, antiepilettic drug intake; gonadal-adrenal surgical intervention pathologies. Data regarding demographics, SLEDAI andSLICC organ damage index (SDI) collected. serum their precursor measured ELISA assay, as listed: Progesterone, Diidroepiandrosterone (DHEA), Diidroepiandrosterone-Sulphate (DHEA-S), Allopregnanolone. To appreciate differences between groups, women’s fertile menopausal subgroups formed p-value <0.05 has been set. Results Table 1 reports from whole cohort. Progesterone significantly higher versus HCs (p=0.011). Progesterone-direct metabolite, Allopregnanolone, increased compared both groups (p=0.026) females (p=0.027). Inversely, low DHEA DHEA-S (p=0.025 p=0.005) found. Looking symptoms, titer inversely correlates deficit diagnosis (p=0.04), while depression (62.5% cohort) Allopregnanolone (p=0.042). Moreover, CES-D score (r=0.550, p=0.041) (r=0.712, p=0.004; Figure 1). At multivariate analysis after correction age, disease duration, SDI, confirmed its independent correlation (β=0.712, p=0.004) severity. Conclusion In this study, we describe first time unbalanced most potent neuroactive steroid manifestations. patients, associates that high levels, correlated manifestation. Since appropriate balance is needed optimal brain neuroimmune function, our preliminary observations – needs be validated an extended - open perspective field, where assessment patient could promising diagnostic preclinical research strategy. 1. Demographic clinical characteristics participants (16) HC (8) Age (DS) 48.2 (15.9) 42.1 (10.8) 49 Gender (F, %) 100 Fertile (%) 50 Menopausal Disease yrs median (IQR) 6(2.3-9.3) 6.7(3.0-10.4) 5 (1.8-11) 2 (0-4) Dose PDN mg/daily 9.5 (5.1-14.6) 3.8 (3.2-7) Cognitive disorder Major 62.5 Median value NPSLE/SLE/HCs female. * pvalue ≤ 0,05; ** 0,01 Acknowledgements All staff Rheumatology Unit AOU Cagliari, volunteer donors. Disclosure Interests Maria Maddalena Angioni: None declared, Elisabetta Chessa: alessandra perra: elisa pintus: Alberto Floris: MATTIA CONGIA: Mauro Giovanni Carta: Cauli: Matteo Piga Speakers bureau: GSK, Consultant of: GALAPAGOS, ASTRAZENECA.