Background: our preliminary data demonstrated that expression and activity of P2X7R was impaired in Systemic Lupus Erythematosus (SLE) and associated with a reduced production of IL-1 β 1 . Serositis is a typical manifestation of SLE characterized by a marked inflammation, which has been suggested to be an “ inflammasomedriven ” manifestation. Objectives: to investigate the role of 1513A>C (rs3751143) and 489C>T (rs208294)SingleNucleotidePolymorphisms(SNPs)whicharedifferentlyassoci-atedwithlossorgainoffunction,respectively,ofP2X7R,apotentactivatorofthe NLRP3 inflammasome and IL-1 β release, in patients with SLE and with a history ofserositis(SLE-S). Methods: DNA was extracted from whole blood and used for evaluation of 2 P2X7R SNPs (1513A>C and 489C>T). Considering the combined action of these two SNPs, the overall activity of P2X7R was divided, into three groups: GOF (gain of function), normal function (NF), and LOF (loss of function). In addition, peripheral blood mononuclear cells (PBMCs) were isolated from venous blood and employed to evaluate P2X7R and NLRP3 expression by RT-PCR, assess P2X7R activity as Benzoyl ATP (BzATP)-induced intracellular Calcium ([Ca2+]i) increments and evaluate in vitro IL-1 β following stimulation with lipopolysaccharide (LPS) andBzATP,eitherseparately orincombination. Results: 33 SLE patients (pts), 11 with (SLE-S) and 22 without serositis (SLE-NS) were enrolled. Mean age was 40.9±10.9 years and disease duration was 135.3± 108.6 months. No significant difference in disease activity and clinical characteristic was found between the two groups (table 1). Evaluating 1513A>C SNP, 20 pts were positive for A/A and 13 for A/C phenotype respectively, while in case of 489C>T SNP, 7 pts