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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-1β1. Serositis is a typical manifestation of SLE characterized by a marked inflammation, which has been suggested to be an “inflammasome driven” manifestation. Objectives: to investigate the role of 1513A>C (rs3751143) and 489C>T (rs208294) Single Nucleotide Polymorphisms (SNPs) which are differently associated with loss or gain of function, respectively, of P2X7R, a potent activator of the NLRP3 inflammasome and IL-1β release, in patients with SLE and with a history of serositis (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-1β following stimulation with lipopolysaccharide (LPS) and BzATP, either separately or in combination. 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 presented C/C, 12 C/T and 14 T/T phenotype with a comparable distribution between SLE-NS and SLE-S (table 1). After combination of different phenotypes, 9 pts presented normal function (NF), 22 gain of function (GOF) and 2 loss of function (LOF) with no significant difference between SLE-S and SLE-NS (table 1). P2X7R activity, (evaluated as IL-1 β production and [Ca2+]i increments,) and expression (evaluated with RT-PCR) were comparable between SLE-S and SLE-NS. No significant difference was found between expression and activity of P2X7R and NLRP3 and the two SNPs evaluated (table 2). Conclusion: our data indicate that the 1513A>C and 489C>T SNPs do not seem linked with reduced activity and expression of P2X7R that we previously observed in our cohort of lupus patients. Furthermore, no significant association was found between expression of these SNPs and development of serositis. References [1] P2X7 receptor in systemic lupus erythematosus (SLE). Exploring a novel pathogenetic pathway in lupus related serositis. F. Furini. Ann Rheum Dis, volume 77, supplement Suppl, year 2018, page A871 Disclosure of Interests: Federica Furini: None declared, Anna Lisa Giuliani: None declared, Mattia Erminio Parlati: None declared, Marcello Govoni Paid instructor for: Pfizer, Roche, Speakers bureau: Pfizer, Abbvie, MSD, Roche, Eli-Lilly, Celgene, Sanofi, Janssen, Francesco Di Virgilio: None declared, Alessandra Bortoluzzi: None declared

Background Antisynthetase syndrome (ASSD) is an autoimmune disease characterized by the clinical triad arthritis, myositis, and interstitial lung disease (ILD). As in inflammatory myopathies, nailfold videocapillaroscopy (NVC) alterations have been sporadically described also in ASSD patients, but no elucidating data are available. Objectives To investigate the possible specific NVC features of ASSD patients. Methods Within the framework of a multicenter study, we retrospectively analyzed NVC images of ASSD patients, after excluding patients with overlap syndrome with systemic sclerosis. Two operators in a blind manner re-evaluated all patients with at least one image per finger. For each patient, we examined number of capillaries (mean number of capillaries per mm in the distal row), enlarged and giant capillaries, micro-hemorrhages, avascular areas, ramified capillaries, and the presence of a scleroderma (SSc)-like pattern, according to Manfredi et al. Finally, we correlated NVC features with clinical and serological findings of ASSD patients. Results The NVC of 54 ASSD patients were analyzed (males/females 1/6.8, mean age 55.79, CI95% 51.9–59.9 years, mean disease duration 59.4, CI95% 27.9–90.9 months). Raynaud9s phenomenon (RP) was recorded in 51.9% of patients, arthritis in 79.6%, myositis in 53.7%, and ILD in 92.6%. NVC alterations were observed in 53.7% of AASD patients. Nineteen patients (35.2%) showed a SSc-like pattern; the main features were disarrangement of hairpin and angiogenetic aspects (42.6%), avascular areas (38.9%), giant capillaries (27.6%), and microhemorrhages (20.4%). Finally, the mean number of capillaries was reduced (7.8±2/mm). No significant association was recorded between SSc-like pattern and the presence of arthritis, myositis, and ILD, nor with RP. Among other NVC features, angiogenesis was significantly associated to female gender (p=0.031), while microhemorrhages were inversely associated to the presence of arthritis (0.033). No association was observed between NVC features and autoantibodies profile. Of interest, in 58% of patients with ILD we observed at least a NVC alteration vs no patients without ILD (p=0.04). Finally, in patients with RP NVC alterations were recorded in 15/28 patients (53.6%) and a SSc-like pattern in 11/28 (39.3%), while only 57.9% of patients with SSc-like pattern had a clinically manifest Raynaud9s phenomenon. Conclusions Despite preliminary, the present is the first study concerning NVC in AASD patients. Regardless of the presence of Raynaud9s phenomenon, NVC alterations are frequently observed; in particular, a SSc-like pattern is recorded in more than 1/3 of patients. NVC should be performed in all ASSD patients at diagnosis regardless of the presence of RP in the patient history and during follow-up. ASSD should be always considered in the screening of RP. A prospective multicenter study has been planned to identify specific patterns and possible associations between NVC findings and clinical and serological features of ASSD. References Manfredi A, et al. 2015. Sebastiani M, et al. 2014. Disclosure of Interest None declared

Background The occurrence of osteoporosis (OP) and fragility fractures (FF) is a frequent comorbidity in patients with systemic lupus erythematosus (SLE), mainly due to the concomitant presence of many risks factors for secondary osteoporosis (drugs, gender, concomitant diseases). The use of corticosteroids (CS) increases the risk of osteoporosis induced by corticosteroid (GIOP) and FF [1]. Denosumab is monoclonal antibody that binds to RANKL, inhibiting osteoclast formation and activation, used for both male and women OP to prevent FFx [2,3]. Previous RCT [2] reported a numerically higher serious adverse events of infections in the denosumab users. In particular severe skin infections were significantly more frequent [4]. The possible increase in infection risk might be a concern in subjects treated with CS. The use of denosumab in SLE with GIOP patients is recently reported in 17 cases within a RCT [5]. Anyway, no data regarding the tolerability and disease activity during therapy were reported Objectives Our aim was to analyze the prevalence, the tolerability, and relevant changes in disease activity or damage in a cohort of SLE patients treated with denosumab Methods among all SLE patients currently followed in two referral Center we selected the ones that received at least one dose of denosumab. Clinical, serological manifestations, concomitant diseases and therapies were collected from clinical charts. Damage index (SDI), activity index (SLEDAI-2K) were calculated when denosumab was introduced (first cycle) and at the last evaluation (last cycle). For statistical analysis Chi-squared test or Fisher exact test was used Results Among 793 patients in our cohorts, 21 (2.6%) were treated with denosumab. Demographic data reported a female prevalence (19 cases,90%), mean age at onset of 38±12years, mean duration of disease of 28±10years and mean follow-up of 21±7.8years; most frequent manifestations were arthritis (90%), cutaneous (67%) and neurological (67%). All patients were still treated with CS (mean duration of 25±6.8 years) with a daily dose of 8.5±3.5mg/day. Other risk factors for OP were present in the majority of them: drugs (anticoagulants in 6pts, cyclosporin in 3 and antiepileptic in 2), chronic kidney disease (CKD) (4pts), hypovitaminosis D (15pts), anorexia, celiac disease and hemochromatosis (1pt, each). Indication for denosumab was OP with FFx in 17 cases: denosumab was used for a new FF during biphosphonates or after teriparatide. In the other 4 the indication was primary prevention with contraindications at the use of biphosphonates for concomitant severe CKD. Mean duration therapy was 4 cycles (range 1–8): data regarding disease activity, damage and adverse events are reported in table 1. No new FFx developed in any of the included patients at the last evaluation available. Conclusions In our cohorts denosumab is still used in few selected patients. However it could be considered as a valid option in GIOP patients because it was globally well tolerated and in our cohort it9s efficacy in the prevention of new fragility fractures was confirmed References Gudbjornsson, et al. Ann Rheum Dis 2002;61,32–36. Cummings SR et al. N Eng J Med 2009; 61:756–65. Austin M et al. J Bone Miner Res 2012;27:687–93. Watts NB, Osteoporos Int 2012;23:327–37. Mok CC, et al. Bone 2015;75:222–8. Disclosure of Interest None declared