Search

INTRODUCTION Like other autoimmune diseases, systemic sclerosis (SSc) has been described to be associated with accelerated atherosclerosis (ATS). Before clinical manifestations of cardiovascular disease (CVD) occur, subclinical ATS can be investigated in different ways. AIM To evaluate the presence of subclinical ATS in a group of patients with SSc, and to identify different risk profiles among patients. METHODS Subclinical ATS was reviewed in 43 SSc patients and 27 healthy controls, using 2 methods: carotid ultrasound and flow mediated dilation (FMD) of the brachial artery. RESULTS Plaques were statistically more frequent in SSc patients than in controls (65% vs 30%, P = .006); intima-media thickness of common carotid artery (CCA-IMT) resulted in statistically higher (median value 0.8 mm vs 0.55 mm; P

The concern about the offspring’s health is one of the reasons for a reduced family size of women with rheumatic diseases (RD). Increased risk of autoimmune diseases (AD) and neurodevelopmental disorders (ND) has been reported in children born to patients with RD. Within a nationwide survey about reproductive issues of women with RD, we aimed at exploring the long-term outcome of their children. By surveying 398 patients who received their diagnosis of RD during childbearing age (before the age of 45), information about the offspring were obtained from 230 women who declared to have had children. A total of 148 (64.3%) patients were affected by connective tissue diseases (CTD) and 82 (35.7%) by chronic arthritis. Data on 299 children (156 males, 52.1%; mean age at the time of interview 17.1 ± 9.7 years) were collected. Twelve children (4.0%), who were born to patients with CTD in 75% of the cases, were affected by AD (8 cases of celiac disease). Eleven children had a certified diagnosis of ND (3.6%; 6 cases of learning disabilities); 9 of them were born to mothers with CTD (5 after maternal diagnosis). No association was found between ND and prenatal exposure to either maternal autoantibodies or anti-rheumatic drugs. Absolute numbers of offspring affected by AD and ND were low in a multicentre cohort of Italian women with RD. This information can be helpful for the counselling about reproductive issues, as the health outcomes of the offspring might not be an issue which discourage women with RD from having children.

Specific indices are not available to evaluate systemic lupus erythematosus (SLE) joint involvement; indeed, the application of indices validated for rheumatoid arthritis has been suggested. We evaluated the usefulness of organ specific composite indices, i.e. the Disease Activity Score on 28 joints (DAS28), Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), and the ratio of swollen to tender joints (STR), to assess SLE joint activity by analyzing the correlation between these indices and ultrasonography (US) inflammatory status. We evaluated SLE patients with arthralgia and/or arthritis: the above-mentioned indices were calculated and the SLE Disease Activity Index 2000 (SLEDAI-2k) was applied to assess global disease activity. US of I–V metacarpophalangeal, I–V proximal interphalangeal, wrist, and knee bilateral was performed. Synovial effusion/hypertrophy and power Doppler findings were scored according to a semi-quantitative scale (0–3) to obtain an inflammatory total score (0–216). One hundred and six patients (M/F 7/99, median age 49.5 years (IQR 17.0), median disease duration 8.5 years (IQR 17.0)) were enrolled. We identified a positive correlation between US score and DAS28-CRP ( r = 0.3, p = 0.007), STR ( r = 0.42, p = 0.0005), SDAI ( r = 0.33, p = 0.02), CDAI ( r = 0.29, p = 0.03); US score reflected different levels of clinimetric joint activity. In conclusion, we suggest the ability of composite indices in detecting SLE joint inflammation and their possible real-life use.

Objective We investigated the genetic diversity, molecular epidemiology and evolutionary dynamics of Staphylococcus aureus (SA) isolated from SLE patients by means of phylogenetic analysis. Methods Consecutive SLE patients (ACR 1997 criteria) were enrolled: clinical/laboratory data were collected and nasal swab for SA identification was performed. On the basis of the translation elongation factor (tuf) gene, a phylogenetic analysis was performed to investigate relationships and to assess significant clades. Selective pressure analysis was used to investigate the evolution of the SA tuf gene. The gene sequences from non-SLE individuals, downloaded from the GenBank database, were compared through phylogenetic analysis with the tuf gene from SLE patients. Results We enrolled 118 patients [M/F 10/108; median (interquartile range (IQR)) age 45.5 (13.2) years; median (IQR) disease duration 120 (144) months]. Twenty-four patients (20.3%) were SA carriers (SA+), three of them MRSA. SA+ SLE showed significantly higher SLEDAI-2k values [SA+: median (IQR) 2 (3.75); SA−: 0 (2); P = 0.04]. The phylogenetic analysis, restricted to 21 non-MRSA SA+, revealed a statistically supported larger clade (A, n = 17) and a smaller one (B, n = 4). Patients located in clade A showed a significantly higher prevalence of joint involvement (88.2%) in comparison with clade B (50.0%, P Conclusion We suggest a possible role of SA nasal carriage status in SLE disease activity. Moreover, our findings support the hypothesis that bacterial genetic variants may be associated with specific disease features.

Objective SLE is an autoimmune disease, mainly affecting women of childbearing age, with possible impact on pregnancy. In this study, we evaluated pregnancy outcomes in all pregnant patients affected by SLE, followed in the context of a rheumatology/gynaecology multi-disciplinary team. Methods Since 2008, we evaluated 70 consecutive pregnancies occurring in 50 SLE patients referring to the Lupus Clinic of Sapienza University of Rome; as controls we evaluated 100 consecutive pregnancies in 100 women without autoimmune diseases. Results By comparing SLE patients and controls, we did not find differences in terms of pregnancy outcomes, except for the occurrence of small for gestational age, which was significantly higher in the SLE group (22.8% vs 11%, P =0.003). Small for gestational age was associated with the positivity for anti-dsDNA, anti-Sm and anti-RNP (P =0.009, P =0.02, P =0.002, respectively). A disease flare was reported in 28 pregnancies (40%) and in 31 puerperium periods (44.3%). Flare during pregnancy was associated with anti-SSA (P =0.02), while puerperium relapse with previous MMF treatment (P =0.01) and haematological flare during pregnancy (P =0.03). Conclusion The present study confirms how pre-gestational counselling and a multi-disciplinary approach could result in positive pregnancy outcomes for SLE patients. The high percentage of disease relapse justifies even more the need for multi-disciplinary management.

Background ICIs have strongly improved the outcome of NSCLC patients. However, primary and secondary resistance occur during treatment in most of the patients, with several of them developing fast progressions. Autoantibodies can be related with a dysfunctional immune system, although their association with immune-based anti-cancer therapies has never been investigated. Moreover, so far no reliable predictive factor is currently available to aid in treatment selection. CD137+T-cells are largely known to be the anti-tumor activated effector cells, but they have never been associated with the response to immunotherapies. Methods Forty-two patients with metastatic NSCLC receiving anti-PD-1 ICIs at Sant'Andrea Hospital and Policlinico Umberto I, from June 2016 to September 2018 were enrolled. Circulating levels of IgM-Rheumatoid Factor were evaluated at baseline and correlated with patients clinical response following the anti-PD-1 treatment. IgM-RF interaction and effect on T-cells in vivo and in vitro were investigated. Findings IgM-RF in NSCLC patient sera strongly predicted the development of early progression to ICIs. Also, a significant reduction of progression-free survival rate in anti-PD-1 treated patients could be identified when patients were stratified based on IgM-RF positivity and titers. IgM-RF bound preferentially circulating naive and central memory T-cells and a significant reduction of CD137+ anti-tumor T effector cells was found in IgM-RF positive patients. In addition, a higher percentage of CD137+T-cells in peripheral blood of NSCLC patients at baseline resulted as a strong independent prognostic factor for a better outcome in terms of PFS and OS after the anti-PD-1 treatment. Furthermore, T-cells exposed to IgM-RF showed a robust defect in their migratory ability in response to CCL19 chemokine. Interpretation In this study we showed that serum IgM-RF can be regarded as predictive factor for the development of early progression and prognostic factor of a reduced progression-free survival and overall-survival in anti-PD-1 treated NSCLC patients. The ability of IgM-RF to bind naive and central memory T-cells and impair their migration could make account for the reduction of the tumor-reactive CD137+ T-cells population that may cause a non-effectiveness of these T-cells targeting drugs. Fundings AIRC, MIUR and Sapienza University of Rome.

The aim of the study was to investigate the presence of subclinical vascular damage in polymyalgia rheumatica (PMR). We enrolled PMR patients having major cardiovascular risk factors (MCVRF) and, as controls, patients with MCVRF. All underwent: color Doppler ultrasound to evaluate the common carotid intima-media thickness (IMT), the anterior–posterior abdominal aortic diameter (APAD), and the prevalence of carotid artery stenosis; the cardio-ankle vascular index (CAVI) to measure arterial stiffness together with the ankle-brachial index (ABI) to investigate the presence of lower-extremity peripheral arterial disease. Finally, we measured the serum levels of adipocytokines implicated in vascular dysfunction. As a result, 48 PMR and 56 MCVRF patients were included. An increase of IMT (1.07/0.8–1.2 vs 0.8/0.8–1.05; p = 0.0001), CAVI (8.7/7.8–9.3 vs 7.6/6.9–7.8; p 2 = 0.845 and r2 = 0.556, respectively; p

Backgrounds The organization of minor salivary glands (MSG) infiltrates, in patients with Sjögren’s syndrome (SS), associates with disease severity and progression. Aberrant regulation of lymphocyte autophagy is involved in autoimmunity, and in previous work, we provided the first evidence of upregulated autophagy in CD4+ T cells infiltrating SS MSG. The aim of this study was to further explore autophagy in SS infiltrating and circulating lymphocytes and to investigate its role in disease histopathological progression. Methods After collection of 20 SS MSG, the presence of lymphocyte aggregates (foci) and the formation of germinal center (GC)-like structures were observed by H&E and confirmed by immunohistochemistry. The expression of autophagy-related genes, Atg5 and MAP1LC3A, was detected by RT-PCR on microdissected salivary gland tissue and control tonsils. In MSG and tonsils, autophagic lymphocytes were identified by the detection of the autophagosome protein LC3B visualized as LC3 puncta staining by immunofluorescence. Peripheral blood autophagy was assessed by flow cytometry in SS and healthy controls (HC). Results Real-time PCR demonstrated higher expression in the autophagy genes Atg5 and MAP1LC3A in MSG GCs as compared to both small foci (p = 0.0075, p = 0.0002) and GCs from tonsils (p = 0.0001, p = 0.0037). In MSG, LC3 puncta staining was detectable on both CD3+ and CD20+ lymphocytes; in tonsils, LC3 puncta was almost undetectable on all lymphocytes. Compared to HC (n = 20), flow cytometry did not reveal any increase of autophagy in SS circulating lymphocytes (n = 30). Conclusions In SS MSG, lymphocytes’ autophagy is a feature of infiltrating T and B cells and is associated with histological severity. Interestingly, in MSG aberrant regulation of autophagy is detectable in GC-like structures possibly indicating its involvement in the development and persistence of the autoimmune process within the lesions.

Background: Aim of this study was to search for any difference in the outcome of patients with adult onset Still's disease (AOSD) treated with anakinra (ANK) in relation with the interval between disease onset and the start of anti-interleukin(IL)-1 treatment and according with the different lines of ANK treatment. Patients and Methods: One hundred and forty-one AOSD patients treated with ANK have been retrospectively assessed. Statistically significant differences (p < 0.05) were analyzed in the frequency of ANK effectiveness, primary or secondary inefficacy to ANK and rate of resolution of clinical and laboratory AOSD manifestations after 3, 6, and 12 months since ANK treatment according with different lines of treatment and different times between AOSD onset and start of ANK. Results: No significant differences were identified in the ANK effectiveness and frequency of primary or secondary inefficacy for patients starting ANK within 6 months (p = 0.19, p = 0.14, and p = 0.81, respectively) or 12 months (p = 0.37, p = 0.23, and p = 0.81, respectively) since AOSD onset compared with patients starting ANK thereafter; no significant differences were identified in ANK effectiveness and primary or secondary inefficacy according with different lines of ANK treatment (p = 0.06, p = 0.19, and p = 0.13, respectively). Patients starting ANK within 6 and 12 months since AOSD onset showed a significantly quicker decrease of erythrocyte sedimentation rate and C-reactive protein than observed among patients undergoing ANK treatment after 6 and 12 months. The number of swollen joints at the 3 month follow-up visit was significantly lower among patients undergoing ANK within 6 months since AOSD onset (p = 0.01), while no significance was identified at the 6 and 12 month assessments (p = 0.23 and p = 0.45, respectively). At the 3 and 6 month visits, the number of swollen joints was significantly higher among patients previously treated with conventional and biological disease modifying anti-rheumatic drugs (DMARDs) compared with those formerly treated only with conventional DMARDs (p < 0.017). Conclusions: Clinical and therapeutic outcomes are substantially independent of how early ANK treatment is started in AOSD patients. However, a faster ANK effectiveness in controlling systemic inflammation and resolving articular manifestations may be observed in patients benefiting from IL-1 inhibition as soon as after disease onset.

Background:Systemic Lupus Erythematosus (SLE) related arthritis has been traditionally defined non-erosive and then considered a minor manifestation. Thanks to the application of more sensitive imaging techniques, such as ultrasonography (US), erosive damage has been identified in up to 40% of SLE patients with joint involvement, suggesting the need for more appropriate treatment (1). Antibodies directed against citrullinated and carbamilated proteins (ACPA and anti-CarP, respectively) have been associated with erosive damage and then proposed as biomarkers for this more aggressive phenotype (2).Objectives:Here, we evaluated a large SLE cohort with joint involvement by using cluster analysis, in order to identify the disease phenotype associated with erosive arthritis.Methods:For this analysis, we enrolled consecutive SLE patients (ACR 1997 criteria) with a clinical history of joint involvement (arthritis/arthralgia). Clinical and laboratory data were collected in a standardized computerized electronically filled form, including demographics, past medical history with the date of diagnosis, co-morbidities, previous and concomitant treatments, serological status. The presence of rheumatoid factor (RF), ACPA and anti-CarP was investigated by ELISA test. Erosive damage was assessed by ultrasonography at level of metacarpophalangeal, proximal interphalangeal and metatarsophalangeal joints (MyLab Eight Exp, Esaote, Florence, Italy). Data have been analysed by hierarchic cluster analysis (SPSS program, IBM).Results:We enrolled 203 patients [M/F 12/191, median age 46.0 years (IQR 18); median disease duration 120.0 months (IQR 108)]. Erosive damage was identified in 53 patients (26.1%), all of them referring at least one episode of arthritis during disease course. Moving on autoantibodies status, RF was positive in 29.5%, anti-CarP in 28.5% and ACPA in 11.2%. The univariate analysis demonstrated a significant association between US-detected erosive damage and anti-CarP (p=0.01), ACPA (p=0.03), and renal manifestations (p=0.03). In Figure 1 we reported the dendrogram obtained from cluster analysis, allowing the identification of four cluster. Positivity for ACPA, anti-CarP, erosive damage, Jaccoud’s arthropathy and renal manifestations were allocated in the same cluster. Interestingly, RF resulted allocated in a different cluster, including ENA, anti-SSA and anti-SSB antibodies.Conclusion:The application of cluster analysis allowed the identification of a specific SLE phenotype, characterized by erosive damage, renal manifestations and positivity for anti-CarP and ACPA. We could speculate about the presence of a shared pathogenic mechanism, involving NETosis, contributing to nephritis and erosive arthritis.References:[1]Ceccarelli F et al. Semin Arthritis Rheum 2017[2]Ceccarelli F et al. Arthritis Res Ther 2018Disclosure of Interests:Fulvia Ceccarelli: None declared, Francesco Natalucci: None declared, Carlo Perricone: None declared, enrica cipriano: None declared, Carmelo Pirone: None declared, Giulio Olivieri: None declared, Tania Colasanti: None declared, Francesca Romana Spinelli Grant/research support from: Pfizer, Consultant of: Novartis, Gilead, Lilly, Sanofi, Celgene, Speakers bureau: Lilly, cristiano alessandri Grant/research support from: Pfizer, Guido Valesini: None declared, fabrizio conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi

Rheumatoid arthritis (RA) is a chronic inflammatory disease with increased risk of cardiovascular events and mortality that can be attributed to accelerated atherosclerosis. This pilot study aimed to investigate if changes in blood parameters were compatible with atherosclerotic events in RA patients. To this aim, 45 RA women (aged more than 18 years), and 25 age and gender-matched healthy donors (HD) were included. Biomarkers of oxidative stress, platelet activation and platelet aggregation were analysed in RA patients at baseline and after six months of treatment with disease modifying anti-rheumatic drugs (DMARDs). Flow cytometry analysis revealed that ca. 4% of platelets was in activated state (evaluated in term of Annexin V and PAC-1 positivity) in RA patients at baseline, and that the 76% of platelets displayed mitochondrial hyperpolarization. Moreover, platelets from RA patients at baseline aggregated more than those from HD after whole blood treatment with adenosine diphosphate. Interestingly, platelet aggregation in patients at baseline positively correlated with disease activity measured by DAS28 score. After six months of treatment with DMARDs, platelet activation and platelet aggregation reached values comparable to those of HD. Our preliminary data suggest that platelets might play an active role in the atherosclerosis occurring in RA patients.

Objective To establish clinical consensus for the optimal placement of TNF inhibitor (TNFi) in DMARDs-naive RA patients. Methods The steering group was composed of 15 Italian rheumatologists expert in the field of RA, who proposed and selected by consensus the clinically relevant questions on the role of TNFi treatment in DMARDs-naive RA patients. The question was rephrased according to the population, intervention, comparison and outcome statement. The available scientific evidence on this topic were collected by updating the systematic literature reviews used for the EULAR 2013 recommendations up to January 2016. The aspects evaluated in the studies concerned clinical efficacy, radiographic structural damage and safety. After the systematic literature review the expert panel formulated a consensus statement, and a modified Delphi panel evaluated the level of agreement between panellists (strength of recommendation). Results From a total of 1080 records we have included 6 studies, 2 randomized clinical trials and 4 open-label extension trials. Evidence from publications generated three statements for the final consensus document. The systematic literature review and the consensus statements developed showed that, for patients with early RA and in the presence of a treat-to-target strategy, the immediate use of anti-TNFi compared with an early (within 12 weeks) step-up to anti-TNF therapy did not confer a significant advantage regarding clinical, functional and radiographic outcomes. Conclusion The most appropriate placement of the TNFi therapy in the treatment algorithm of early RA still remains a challenging clinical question that needs to be further addressed.

In a previous report of two married cohabiting couples affected by polymyalgia rheumatica (PMR), we noticed that the wife of one couple and both members of the other couple suffered from symptomatic diverticular disease (DD), whose diagnosis was made before the onset of PMR. We investigated whether DD might be a risk factor for the development of PMR. We conducted a case-control study informed on a database containing the prospectively collected medical records of consecutive PMR patients. Among comorbidities, attention was focused on symptomatic DD, provided that the diagnosis had been made by colonoscopy and/or computed tomography scan. As controls, we identified one control per case at random among those matched by age and sex attending the ophthalmic and orthopedic outpatient clinics, as long as a PMR diagnosis had been excluded. A logistic regression model was used, following a multiplicative model, and results were presented as odds ratio (OR) and 95% confidence intervals (95% CI). The most frequent comorbidities in the two groups of patients (121 cases and 121 controls) were chronic coronary artery disease, atrial fibrillation, diabetes mellitus, hypertension, DD, hypercholesterolemia, osteoporosis, chronic obstructive pulmonary disease, gastroesophageal reflux disease, and cholelithiasis. The association between PMR and DD (OR = 4.06; 95% CI: 1.76-9.35) was by far stronger than that found comparing PMR with the other comorbidities. The chronic bowel inflammation induced by dysbiosis in patients with symptomatic DD could be a critical immunopathological mechanism supporting the development or exacerbation of PMR in susceptible individuals.

Background Mycophenolate mofetil (MMF) is an immunosuppressive drug currently used to treat Systemic Lupus Erythematosus (SLE). In addition to clinical efficacy, MMF use is also supported by a favorable profile of tolerance, with main side effects being nausea, diarrhea, headache, and, less frequently, leucopoenia. Acne is a relatively frequent adverse reaction to MMF that requires specific treatment and drug suspension. Investigations Herein, we describe four cases of MMF-induced acne, none reporting past medical history of acne. The patients were diagnosed with SLE and lupus nephritis and treated with MMF. They developed papulo-pustular and nodular skin lesions consistent with acne. The lesions occasionally showed the appearance of macrocomedones or of unusual, nodular, oedematous lesions in gluteal region, or they had abscess-like features. Culture test demonstrated the presence of Staphylococcus Aureus. They resolved after MMF withdrawal and therapy with tetracycline and local pseudomonic-acid. Conclusions Staphylococcus Aureus skin-localized infections inducing inflammatory/infectious acne may be a relatively frequent side-effect of MMF therapy in SLE. As soon as generalized, severe infections, due to Staphylococcus Aureus, may also occur in patients treated with MMF and even if antibiotics therapy is usually relatively effective, at least temporary MMF suspension may be suggested.

The therapeutic approach to CNS demyelination associated to ankylosing spondylitis is a complex issue due to the contraindication of TNF inhibitors in demyelinating diseases. Secukinumab, a human IgG1κ monoclonal antibody that binds and inhibits IL-17A, was recently approved for the treatment of ankylosing spondylitis. We report the clinical cases of two patients affected by a CNS demyelinating disease and ankylosing spondylitis who were successfully treated with secukinumab, providing additional evidence of the feasibility of this therapeutic option when the use of TNF inhibitors is discouraged by challenging comorbidities.

Anti-synthetase syndrome is an autoimmune disease characterized by autoantibodies toward amino acyl-tRNA synthetases (ARS), anti-Jo 1 being the most commonly detected. Muscle damage develops in up to 90% of ARS-positive patients, characterized by a necrotizing myositis restricted to the perifascicular region. This topographic distribution of muscle damage may lead to a misdiagnosis of dermatomyositis (DM) at muscle biopsy. We compared morphological, immunohistochemical, and histoenzymatic features of muscle from ARS-positive patients (n = 11) with those of DM (n = 7) providing clues for their differential diagnosis. In addition, we evaluated markers of mitochondrial damage to provide a further distinction between these two entities. Necrosis occurred in the majority of ARS patients, mainly located in the perifascicular region. It was often limited to small foci of fibers, always associated with myocyte regeneration. This last often overwhelmed necrosis, representing occasionally the main finding. In DM, necrosis/regeneration was scarce while the peculiar feature was a diffuse atrophy of perifascicular fibers. These last showed decreased cytochrome c oxidase (COX) stain and mitochondrial DNA depletion, consistent with mitochondrial dysfunction. In contrast to DM, ARS displayed scattered COX-deficient fibers, not restricted to the perifascicular region. This feature occurred in up to 91% of patients, being prominent only in two.

Background: The primary objective of the present study was to provide an assessment of NK cells in patients with ANCA-associated vasculitis (AAV). Methods: Patients were classified based on the presence or absence of ANCAs and compared to healthy controls (HC). By multiparameter flow cytometry, we evaluated the number and proportion of NK cells (CD3-CD56+) and the CD56dim, CD56bright, CD56dimCD57bright subsets; TLR2 and TLR9 expression; intracellular IFN-γ production upon stimulation with TLR2 and TLR9 ligands; degranulation activity; serum cytokines; immunohistochemical staining of available biopsies. Results: No differences in the number and proportion of NK cells between patients and HC were observed, except for a lower proportion of CD56dim subset in ANCA-negative patients than in HC (P=0.02). With respect to HC, TLR2 expression levels were reduced in NK cells from ANCA-negative patients (P=0.03), in the CD56dim subset of ANCA-positive (P=0.02) and ANCA-negative patients (P=0.01), in the CD56bright subset of ANCA-positive patients (P=0.007), and in the CD56dimCD57bright subset of ANCA-positive (P=0.04) and ANCA-negative patients (P=0.03). No differences between patients and HC were found concerning IFN-γ production and degranulation activity. IL-22 levels were lower in ANCA-positive patients than in HC (P=0.01). The immunohistochemical analysis showed sporadic CD56+ cells in one renal biopsy, and a diffuse and moderate infiltrate of IL-22+ cells in all renal biopsies and in skin tissue. Conclusions: Our data suggest a role of infectious stimuli triggering NK cells in AAV pathogenesis. Poor detection of NK cells in affected tissues suggests a marginal involvement in local inflammatory responses. This article is protected by copyright. All rights reserved.

Author(s): Clowse, Megan EB; Wallace, Daniel J; Furie, Richard A; Petri, Michelle A; Pike, Marilyn C; Leszczynski, Piotr; Neuwelt, C Michael; Hobbs, Kathryn; Keiserman, Mauro; Duca, Liliana; Kalunian, Kenneth C; Galateanu, Catrinel; Bongardt, Sabine; Stach, Christian; Beaudot, Carolyn; Kilgallen, Brian; Gordon, Caroline; EMBODY Investigator Group | Abstract: ObjectiveEpratuzumab, a monoclonal antibody that targets CD22, modulates B cell signaling without substantial reductions in the number of B cells. The aim of this study was to report the results of 2 phase III multicenter randomized, double-blind, placebo-controlled trials, the EMBODY 1 and EMBODY 2 trials, assessing the efficacy and safety of epratuzumab in patients with moderately to severely active systemic lupus erythematosus (SLE).MethodsPatients met ≥4 of the American College of Rheumatology revised classification criteria for SLE, were positive for antinuclear antibodies and/or anti-double-stranded DNA antibodies, had an SLE Disease Activity Index 2000 (SLEDAI-2K) score of ≥6 (increased disease activity), had British Isles Lupus Assessment Group 2004 index (BILAG-2004) scores of grade A (severe disease activity) in ≥1 body system or grade B (moderate disease activity) in ≥2 body systems (in the mucocutaneous, musculoskeletal, or cardiorespiratory domains), and were receiving standard therapy, including mandatory treatment with corticosteroids (5-60 mg/day). BILAG-2004 grade A scores in the renal and central nervous system domains were excluded. Patients were randomized 1:1:1 to receive either placebo, epratuzumab 600 mg every week, or epratuzumab 1,200 mg every other week, with infusions delivered for the first 4 weeks of each 12-week dosing cycle, for 4 cycles. Patients across all 3 treatment groups also continued with their standard therapy. The primary end point was the response rate at week 48 according to the BILAG-based Combined Lupus Assessment (BICLA) definition, requiring improvement in the BILAG-2004 score, no worsening in the BILAG-2004 score, SLEDAI-2K score, or physician's global assessment of disease activity, and no disallowed changes in concomitant medications. Patients who discontinued the study medication were classified as nonresponders.ResultsIn the EMBODY 1 and EMBODY 2 trials of epratuzumab, 793 patients and 791 patients, respectively, were randomized, 786 (99.1%) and 788 (99.6%), respectively, received study medication, and 528 (66.6%) and 533 (67.4%), respectively, completed the study. There was no statistically significant difference in the primary end point between the groups, with the week 48 BICLA response rates being similar between the epratuzumab groups and the placebo group (response rates ranging from 33.5% to 39.8%). No new safety signals were identified.ConclusionIn patients with moderate or severely active SLE, treatment with epratuzumab + standard therapy did not result in improvements in response rates over that observed in the placebo + standard therapy group.

Background:Few studies have examined the correlation between clinical demographic and laboratory parameters with peripherical radiological erosive disease in PsA pts.Objectives:To examine the association between clinical, demographical and laboratory data and the presence of radiographic erosions (RE) in the peripheral joints of psoriatic arthritis (PsA) pts.Methods:A cross-sectional study was conducted in consecutive patients with PsA afferring 7 rheumatological italian tertiary care centers. Demographical, clinical, laboratory and imaging data were collected according to a standardized protocol. A patient was considered as affected by erosive disease (ED) if at least one joint presented radiographic erosions at hand and/or feet rx examination. Patients with ED at early rx examination (before 5 y from disease diagnosis) were considered as early ED (EED) pts and pts without ED at 6 y or more rx examination from disease diagnosis were considered as not EED (NEED).The association between the presence of joint erosions and demographical, clinical and laboratory data was assessed using logistic regression analysis. The results were expressed in terms odds ratios (OR), and 95% confidence intervals (CI).Results:Rx hand and feet examination were available for analysis in 492/794 (39.9 % females, mean age 53.3 ± 13.2 y, mean PsA duration 16.9 ± 16.8 y, ED 171 pts). 48 pts had EED and 133 pts had NEED. At univariate analyses factors significantly associated with EED (p < 0.20) were PsA duration (OR=0.979,95%CI 0.953-1.006, p = 0.119), diagnostic delay (OR=1.077, 95%CI 1.018-1.138, p = 0.009), history of peripheral enthesitis (OR=2.308,95%CI 0.904-5.888, p= 0.080), hypertrigliceridemia (OR=2.756,95%CI 0.997-7.618, p = 0.0.051), hypercholesterolemia (OR=1.687, 95%CI 0.777-3.661, p = 0.186), hyperuricemia (OR=0.450, 95%CI 0.174-1.166, p = 0.10), use of biological agents (OR=1.712, 95%CI 0.873-3.355, p=0.118). Factors significantly associated with EED at multivariate regression analyses were diagnostic delay (OR = 1.11, 95% CI: 1.01, 1.22), history of enthesitis (OR = 3.15, 95% CI: 1.23, 8.22), use of therapy with biological agents (OR = 3.60, 95% CI: 1.31, 9.85) with protective effect of hyperuricemia (OR = 0.25, 95% CI: 0.07, 0.90).Conclusion:The presence of EED in a group of consecutive PsA patients is correlated to diagnostic delay and history of enthesitis. Longitudinal study may confirm these associations.Disclosure of Interests:Maria Grazia Catanoso: None declared, Pierluigi Macchioni: None declared, Antonio Marchesoni Speakers bureau: Abbvie, Pfizer, UCB, Novartis, Celgene, Eli Lilly, Salvatore D’Angelo Speakers bureau: AbbVie, Biogen, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, Sanofi, and UCB, Roberta Ramonda Speakers bureau: Novartis, Celgene, Janssen, Pfizer, Abbvie, Lilly, Alberto Cauli: None declared, fabio perrotta: None declared, Roberto Bortolotti: None declared, mariana lofrano: None declared, laura rotunno: None declared, maria grazia lorenzin: None declared, Guido Valesini: None declared, giovanni mathieu: None declared, Giuseppe Paolazzi: None declared, Carlo Salvarani Grant/research support from: consulting and investigator fees from Abbvie, Pfizer, MSD, Roche, Celgene, Novartis, Consultant of: consulting and investigator fees from Abbvie, Pfizer, MSD, Roche, Celgene, Novartis

Background:Therapeutic approach of rheumatoid arthritis (RA) patients has been enriched by the introduction of small molecules. In particular Jak inhibitors (JAKi), baricitinib and tofacitinib, demonstrated their efficacy in patients naïve or resistant to biological treatments in randomized controlled trials. Moreover, these drugs seem to be able to prevent radiographic progression. To date few data are available from the real life context. Ultrasonographic (US) assessment has became a valid imaging tool in the management of RA patients in clinical practice, allowing the evaluation of joint inflammatory status. Together with clinimetric assessment, US could provide a comprehensive assessment of drug response.Objectives:In the present study we aimed at assessing the early response to JAKi treatment by using musculoskeletal US.Methods:In this prospective longitudinal study, we collected data about all consecutive active RA patients starting treatment with JAKi. RA was diagnosed according to the 2010 ACR/EULAR criteria. At each visit, clinical and laboratory data were collected in a standardized and computerized form, including demographics, past medical history, co-morbidities, previous and concomitant treatments. According with study protocol, all patients underwent clinical and US assessment at the following time-points: baseline (T0), 4 weeks (T1) and 12 weeks (T2). Clinical evaluation included tender and swollen joint counts (0-28), patients global health assessment. C-reactive protein (CRP) levels were registered and disease activity was calculated by disease activity score (DAS) in 28 joints by using CRP (DAS28-CRP). A systematic multiplanar grey-scale and power Doppler (pD) US examination was performed by using MyLab Eight Exp Machine (Esaote, Florence, Italy) at level of 22 joints (bilateral I-V metacarpophalangeal, I-V proximal interphalangeal, wrist). According with OMERACT definitions (1) we assessed the presence of synovial effusion, hypertrophy and pD, that were scored according to a semi-quantitative scale (0-3). A total US inflammatory score (0-198) was obtained by their sum.Results:We enrolled 91 patients [F/M 77/14; median age 60.0 years (IQR 15.5); median disease duration 144 months (IQR 126)]. Of these patients, 54 (59.3%) were treated by baricitinib and the remaining 37 by tofacitinib. At baseline we found a median US inflammatory score of 20 (IQR 18.7) and a median DAS28-CRP of 5.0 (IQR 1.56). US assessment demonstrated significant reduction in the median values of inflammatory score already at T1 [median 13 (IQR 14.7), pConclusion:In the present study, specifically designed to evaluate the US-detected efficacy of JAKi in RA patients, we demonstrated in a real life setting a significant, early and sustained improvement of inflammatory joint status.References:[1]Wakefield et al, J Rheumatol 2005Disclosure of Interests:enrica cipriano: None declared, Fulvia Ceccarelli: None declared, Francesca Romana Spinelli Grant/research support from: Pfizer, Consultant of: Novartis, Gilead, Lilly, Sanofi, Celgene, Speakers bureau: Lilly, Cristina Garufi: None declared, Ilaria Duca: None declared, Silvia Mancuso: None declared, cristiano alessandri Grant/research support from: Pfizer, Manuela Di Franco: None declared, Roberta Priori: None declared, Valeria Riccieri: None declared, Rossana Scrivo: None declared, Carlo Perricone: None declared, Guido Valesini: None declared, fabrizio conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi

Background:Joint involvement is one of the most common features observed in Systemic Lupus Erythematosus (SLE), potentially involving up to 90% of patients [1]. Several patients’ reported outcomes (PROs) have been employed to measure Quality of life (QoL) in SLE patients, but frequently not specifically developed for SLE patients. More recently, the LupusQoL has been validated, a disease specific questionnaire[2,3].Objectives:We focused at assessing the relationship between musculoskeletal manifestations and QoL in a large SLE cohort, by using the LupusQoL.Methods:SLE patients with a clinical history of joint involvement (arthralgia/arthritis – group A) were enrolled in the present study. SLE diagnosis was performed according to the revised 1997 ACR criteria. As a control group, we enrolled SLE patients without history of joint involvement (group B).Disease activity was assessed by the SLE Disease Activity Index-2000 (SLEDAI-2k). The activity of joint involvement was assessed by using the disease activity score on 28 joints (DAS28ESR). The LupusQoL was administered to the enrolled patients (Group A and Group B). It consists of 34 items referring to eight domains: physical health (PH), pain (P), planning (PL), intimate relationships (IR), burden to others (BO), emotional health (EH), body image (BI) and fatigue (F).Results:Group A included 110 patients [M/F 8/102; median age 49 years (IQR 13), median disease duration 156 months (IQR 216)], while group B included 58 patients [M/F 11/47; median age 40 years (IQR 15), median disease duration 84 months (IQR 108)]. Group A showed a significantly lower disease duration and mean age in comparison with group B (P< 0.001 for both comparisons). As represented in figure 1, group A showed significantly lower values in all LupusQoL domains except for “burden to others” domain. Moreover, we observed an inverse correlation between DAS28ESRand all the LupusQoL domains in group A patients [PH (r=-0.5, P>0.0001), P (r=-0.5, PFigure 1.Conclusion:In the present study, by using a disease specific PRO, we found a poorer QoL in SLE patients with joint involvement in comparison with those without this manifestation. Moreover,DAS28ESRsignificantly correlated with all LupusQol domains, differently from SLEDAI-2k, suggesting the need to evaluate joint involvement with a specific activity index.References:[1]Cervera R et al. Medicine 1993[2]McElhone K. et al. Arthritis Rheum 2007.[3]Conti F et al. Lupus 2014Group (A)Group (B)pPH80,38 ± 21,4362,88 ± 23.28< 0.0001P82,36 ± 25.0862,30± 26.02< 0.0001PL83,04 ± 27.8270,58± 29.450.001IR84,49± 25.9965,36± 36.330.0005BO69,58 ± 28.4663,45± 28.950.129EH71,98 ± 24.6964,69± 23.050.0169F73,69 ± 24.2959,78±26.060.0004B78,14 ± 24.6156,28±30.14Disclosure of Interests:Francesco Natalucci: None declared, Fulvia Ceccarelli: None declared, enrica cipriano: None declared, Giulio Olivieri: None declared, Carlo Perricone: None declared, Francesca Romana Spinelli Grant/research support from: Pfizer, Consultant of: Novartis, Gilead, Lilly, Sanofi, Celgene, Speakers bureau: Lilly, Simona Truglia: None declared, Francesca Miranda: None declared, cristiano alessandri Grant/research support from: Pfizer, fabrizio conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi, Guido Valesini: None declared

Background:Rheumatoid arthritis (AR) is an autoimmune systemic inflammatory disease characterized by chronic synovial inflammation resulting in bone damage and erosions, with consequently functional disability. Currently, attempts for regenerative therapies for osteo-cartilage pathologies have proved unsuccessful. Recently, a “pool” of skeletal stem cells (hSSCs: human skeletal stem cells) able to generating bone cells, has been identified in human bone (1).Objectives:In light of these observations, we aim at characterizing skeletal stem cells in peripheral blood from RA patients candidate to Tofacitinib treatment.Methods:In this pilot study 4 RA patients [4F; mean age 65 years; mean disease duration 19 years] candidate to Tofacitinib treatment and 4 healthy donors (HD), matched by gender and age, were enrolled. Blood samples were collected from each subject of the study, at baseline (T0) and for RA patients, after 1 month of Tofacitinib (T1), to evaluatinghSSC(CD45-, CD146-, CD73+, PDPN+, CD164+) by flow cytometry. For this purpose, we performed on whole blood a negative magnetic selection for CD45 cells. Then, the eluate was labeled with antibodies anti CD146-PE, anti CD73-APC, anti CD164 - FITC and anti-Podoplanin (PDPN) PerCP/Cyanine5.5. The acquisition was performed using a FACS Calibur, which included 100,000 events per sample (Figure 1).Results:ThehSSCspercentage was significantly lower in RA patients than in HD (p = 0.0286). At T1, after treatment with Tofacitinib, meanhSSCspercentage significantly increased from 1.8% to 4.2 % (p = 0.016 vs RA T0) (Figure 2A). Correlation analysis showed a significant indirect relation between the percentage ofhSSCand disease activity measured by DAS28ESR, SDAI and CDAI (Figure 2B).Conclusion:The results of this study demonstrate, for the first time, circulating skeletal stem cells and their reduced expression in active RA patients. Tofacitinib treatment leads to a significant increase inhSSCspercentage. This evidence opens up new perspectives on bone repair mechanisms and on deepening of current therapeutic strategies.References:[1]Chan CKF, Gulati GS, Sinha R, Tompkins JV, Lopez M, Carter AC, Ransom RC, Reinisch A, Wearda T, Murphy M, Brewer RE, Koepke LS, Marecic O, Manjunath A, Seo EY, Leavitt T, Lu WJ, Nguyen A, Conley SD, Salhotra A, Ambrosi TH, Borrelli MR, Siebel T, Chan K, Schallmoser K, Seita J, Sahoo D, Goodnough H, Bishop J, Gardner M, Majeti R, Wan DC, Goodman S, Weissman IL, Chang HY, Longaker MT.Identification of the Human Skeletal Stem Cell.Cell. 2018 Sep 20;175(1):43-56.e21. doi: 10.1016/j.cell.2018.07.029.Acknowledgments:noneDisclosure of Interests:cristiana barbati: None declared, Francesca Romana Spinelli Grant/research support from: Pfizer, Consultant of: Novartis, Gilead, Lilly, Sanofi, Celgene, Speakers bureau: Lilly, cristina garufi: None declared, Ilaria Duca: None declared, fulvia ceccarelli: None declared, Tania Colasanti: None declared, Marta Vomero: None declared, cristiano alessandri Grant/research support from: Pfizer, Guido Valesini: None declared, fabrizio conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi

Background Endothelial-to-mesenchymal transition (EndoMT), a newly recognized type of cellular transdifferentiation, seems to be involved in Systemic Sclerosis (SSc) pathogenesis. In this process endothelial cells lose their specific markers, and acquire a mesenchymal phenotype, thus expressing cell products such as alpha smooth muscle actin (α-SMA) (1,2). Circulating endothelial progenitors cells (EPCs) derive from bone marrow stem cells and contribute to de novo vessels formation. Several studies, although with conflicting results, have shown that EPCs in the peripheral blood of patients with SSc are impaired in their number and function (3). Objectives to assess the expression of α-SMA, possibly associated with a pro-mesenchymal switch (EndoMT) of the circulating Early (CD34+KDR+CD 133+) and Late (CD34+KDR+) EPCs in the peripheral blood of SSc patients and of patients with Very Early Diagnosis of SSc (VEDOSS) compared with healthy controls (HC) using flow cytometry. Methods we enrolled 11 patients (7 SSc and 4 VEDOSS), classified according to the classification criteria for SSc (4) and for VEDOSS not fulfilling SSc criteria (5), and 10 HC. Phenotypic characterization was performed as previously described by Vasa et al. using a FACS Calibur (BD Immunocytometry Systems). EPCs number was expressed as a percentage of cells within the lymphocyte gate. Results we found a significantly higher percentage of α-SMA positive Early EPCs (CD34+KDR+CD 133+αSMA+) in all patients respect to HC (0,06% ±0,03 vs 0,03% ± 0,01; p=0,0149) particularly in VEDOSS patients (0,07%±0,01 vs 0,03±0,01 p=0,008). Moreover, in VEDOSS patients, also the percentage of Early EPCs (CD34+KDR+CD 133+), Late EPCs (CD34+KDR+)and α-SMA positive Late EPCs (CD34+KDR+αSMA+) were significantly higher than in HC (0,05%±0,01 vs 0,03%±0,01 p=0,05; 0,07%±0,01 vs 0,04%±002 p=0,04; 0,06%±0,01 vs 0,04%±0,02 p=0,05). Besides Early EPCs and α-SMA positive Early EPCs percentages seem to be significantly reduced in patients taking iloprost (p=0,05 and p=0,01 respectively), calcium channel blockers (CCB) (p=0,05 and p=0,03) and DMARDs (p=0,017 and p=0,013). Conclusion EndoMT seems to be involved in the pathogenesis of SSc and circulating EPCs seem to be impaired in number and function in SSc patients. In our study we found higher levels of EPCs, in particular α-SMA positive Early EPCs in both groups of patients (SSc and VEDOSS) respect to HC. Thus we can hypothesize a predominant pro-mesenchymal phenotype of this kind of EPCs. This could be considered the expression of the involvement of EPCs in EndoMT process and could better explain the controversial role of EPCs in SSc pathogenesis. Very interesting is the finding of a lower percentage of Early EPCs, and in particular of α-SMA positive Early EPCs, in those patients taking iloprost, CCB and DMARDs, suggesting a potential effect of these drugs on this subgroup of EPCs. References [1] Corallo C, et al. Arthritis Res Ther2016; [2] Manetti M, et al. Ann Rheum Dis2017; [3] Del Papa N, et al. Front. Immunol2018; [4] Van den Hoogen F, et al. Ann Rheum Dis2013; [5] Avouac J, et al. Ann Rheum Dis2011. Disclosure of Interests Katia Stefanantoni Consultant for: Only 1 scientific advice for Italfarmaco in 2016, cristiana barbati: None declared, Carlotta Angelelli: None declared, Greta Pellegrino: None declared, cristiano alessandri: None declared, Guido Valesini: None declared, Valeria Riccieri: None declared

Background: Lupus nephritis (LN) occurs up to 50% of patients affected by Systemic Lupus Erythematosus (SLE) representing one of the major causes of morbidity and mortality in lupus population (1). Kidney biopsy is a fundamental tool for the diagnosis and management of lupus nephritis. The presence of pathological changes such as inflammatory infiltrate in glomeruli and/or in tubulo-interstitium are relevant in terms of prognosis and response to therapy (2). Objectives: The aim of the study was to correlate the clinical and laboratory findings and the response to therapy with presence of glomerular and/or interstitial infiltrate in kidney section of patients with a biopsy-proven LN. Methods: Kidney sections of patients with SLE undergoing a renal biopsy for diagnostically purpose were studied; samples were classified according to the 2004 International Society of Nephrology/Renal Pathology Society classification criteria (3). Clinical, laboratory and histological data were collected in a standardized, computerized and electronically filled form, including demographics, past medical history, autoantibody profile, previous and concomitant treatments. We assessed the disease activity by using SLEDAI-2K and remission in response to therapy was defined as the absence of renal impairment and as a score 0 of renal SLEDAI (proteinuria Results: We evaluated 53 kidney samples from patients with LN (F:M = 51:2, mean age at biopsy 35±7.7 years; mean disease duration at date of biopsy 8±8.3 years). Class IV (46%) was the most common class followed by class III (29%), class II (13%), class V (11.5%) and class VI (0,5%). Tubulo-interstitial infiltrate was found in 33 kidney specimens, with germinal centres (GC)-like features in 13 renal samples (Figure 1). During the follow up (6±3.8 years) the tubulo-insterstitial infiltrate, either diffuse or with GC-like feature, was negatively correlated with renal remission (P=0.03). Conclusion: Assessment and management of patients with LN are greatly facilitated by information obtained by renal biopsy. In the present study we demonstrate that the presence of tubulo-interstital infiltrate is associated with a worse outcome in response to therapy. Our data highlight the importance of tubulo-interstitium damage, scarcely considered in the current classification criteria, since it represents a key point to predict long-term prognosis. References: [1] Schwartz N, et al. Curr Opin Rheumatol. (2014) [2] Giannakakis K, et al. Clinic Rev Allerg Immunol (2011) [3] Weening JJ, et al. J Am Soc Nephrol (2004) [4] Gladman DD, et al. J Rheumatol (2002) [5] Houssiau FA, et al. Arthritis Rheum (2002) [6] Hahn BH, et al. Arthritis Care & Research (2012) Disclosure of Interests: None declared

Background: Cognitive impairment (CI) in Systemic Lupus Erythematosus (SLE) is a frequent neuropsychiatric manifestation affecting several domains, even in apparently asymptomatic patients. Current research revealed that the typical CI pattern affects frontal-subcortical circuit and thus executive functions. The impairment of non-literal language or Pragmatic Language (PL), including metaphors, idioms, inferences or irony has been well described in several conditions such as autism disorders, Parkinson’s disease, brain injury and even in earlier phases of neurodegenerative processes. Even if PL neuro-anatomy remains controversial, correlation between executive dysfunctions and non-literal language involvement has been reported both in traumatic injury and mild cognitive impairment patients. Nonetheless, no specific study has been performed to evaluate PL impairment in SLE patients so far. Objectives: We aimed at assessing the PL domain in a monocentric SLE cohort in comparison to healthy controls, matched to age and education, through a specific battery, BLED [1]. Secondly, we focused attention on possible correlations between CI and clinical and laboratory SLE-related features. Methods: Forty adult patients affected by SLE, according to the ACR criteria, and thirty healthy subjects were enrolled consecutively in this cross-sectional study. The protocol included complete physical examination, extensive clinical and laboratory data collection (comprehensive of demographics, past medical history, co-morbidities, disease activity, chronic damage evaluation, previous and concomitant treatments) and cognitive assessment for five different domains: memory, attention, pragmatic language, executive and visuospatial functions. Self-reported scale for anxiety and depression were performed to exclude the influence of mood disorders on cognitive dysfunction. Results: We enrolled forty Caucasian SLE patients (M/F 3/37; mean±SD age 45.9±10.1 years, mean±SD disease duration 120.8±81.2 months) and thirty healthy subjects (M/F 9/21; mean±SD age 41.3±13 years). According to the low level of disease activity and damage (mean±SD SLEDAI-2K of 1.3±2.3, mean±SD SDI of 0.2±0.5), only 30% of patients was on glucocorticoid treatment at the study entry. PL was the most compromised domain in terms of Mean Domain Z scores (Fig. 1). As regards the Domain Cognitive Dysfunction score, a deficit of PL was observed in 45% of patients and resulted significantly more prevalent than memory, executive and visuospatial functions impairment (P=0.0002, P=0.0002 and P Conclusion: We evaluated for the first time PL in a single center SLE cohort finding a dysfunction in almost half of patients enrolled, significantly more frequent than the other assessed domains. Reference: [1] Rinaldi C, Marangolo P, Lauriola M. “BLED Santa Lucia: Batteria sul Linguaggio dell’Emisfero Destro Santa Lucia” Giunti O.S., 2006. Disclosure of Interests: Carmelo Pirone: None declared, Fulvia Ceccarelli: None declared, Concetta Mina: None declared, Alfredo Mascolo: None declared, Carlo Perricone Speakers bureau: BMS; Lilly, Celgene, Sanofi, Barbara Mazzotta: None declared, Laura Massaro: None declared, francesca spinelli: None declared, cristiano alessandri: None declared, Guido Valesini: None declared, fabrizio conti: None declared

Background: Baricitinib, a newly approved drug for the treatment of patients with moderate to severe rheumatoid arthritis (RA), is a selective inhibitor of Janus kinase 1 and 2. In a patient-centered care, patient-reported outcomes (PROs) are really helpful to better evaluate the disease activity and the response to therapy. Between them, Patient Acceptable Symptom State (PASS) is defined as the highest level of symptoms beyond which patients consider themselves well [1], and consists of a single question with dichotomized answer (yes or no): “Considering all the different ways your disease is affecting you, if you would stay in this state for the next months, do you consider that your current state is satisfactory?”. In randomized controlled trials baricitinib showed significant improvement of pain, fatigue, tiredness and assessment of disease [2]. Objectives: The aim of the present study was to investigate the effect of baricitinib on PASS one month from the beginning of therapy. Further aim was to quantify the time patients needed to reach an acceptable state of health and determine the clinical variables associated with PASS. Methods: Patients affected by RA according to 2010 ACR criteria, starting treatment with baricitinib as clinically indicated, were consecutively enrolled; PASS was determined after 1 month of treatment (T1); days to achieve PASS were estimated at T1; activity indices were calculated after 1 month of therapy and correlated with PASS. Results: Thirty-four RA patients were enrolled (age median-IQR 58-16 years; disease duration median-IQR 144-138 months; DAS-28 median-IQR 5.09-1.92). After 1 month of therapy, 30 of 34 patients achieved PASS, of which 73% in the first 2 weeks of treatment (days to achieve PASS median-IQR 12-22) (figure). At T1, patients achieving PASS, compared to those who did not, reported less pain (median VAS 30/100 vs 72/100, p= 0.025), a better global assessment of disease (median 40/100 vs 72/100, p=0.023), lower CDAI (median 12 vs 31, p= 0.048), SDAI (median 12.8 vs 33.95, p=0.011) and DAS-28 (median 3.67 vs 5.54, p= 0.082). 10 out of 30 PASS positive patients (33%) achieved a DAS-28 low-disease activity or remission at T1 vs 0% of the PASS negative cohort (p= 0.169). Age, disease duration and number of previous bDMARDs did not significantly differ between the two subgroups. Conclusion: Baricitinib was able to induce an acceptable state of health in about 90% of patients after the first month of therapy. The prompt effect of baricitinib on pain and fatigue could partially explain the rapid achievement of PASS, as shown by the decrease of VAS and improvement of the global assessment of disease. References [1] Maksymowych WP, et al. Evaluation and validation of the patient acceptable symptom state (PASS) in patients with ankylosing spondylitis. Arthritis Rheum 2007 [2] Schiff, et al. Patient-reported outcomes of baricitinib in patients with rheumatoid arthritis and no or limited prior disease-modifying antirheumatic drug treatment. Arthritis Res Ther. 2017 Disclosure of Interests: None declared

Background The PDE4-inhibitor apremilast has been recently introduced in the treatment of Psoriatic Arthritis (PsA). It acts by down-regulating intracellular inflammatory mediators synthesis by elevating cAMP levels. Tregs, a subset of FOXP3+ CD4 T cells, play a key role in preventing immune responses and could exert their suppressive function via cAMP (1). Reduced frequencies of circulating Tregs have been observed in inflammatory disorders, nonetheless very few data are available on PsA patients. Objectives We evaluated peripheral Tregs in a cohort of PsA patients treated by apremilast. Methods Seventeen PsA patients (M/F 3/14; median age 56.0 years, IQR 20.0; median disease duration 15.0 years, IQR 11.0) with polyarticular subset treated by apremilast, were evaluated at baseline (T0) and after 6 (T1) and 12 weeks (T1). Clinimetric evaluation included DAS28, DAPSA, CDAI, and SDAI. Moreover, US assessment was performed at wrists, metacarpophalangeal (MCP), and proximal interphalangeal (PIP) joints: synovial effusion/hypertrophy and power Doppler were scored by a semi-quantitative scale (0-3), obtaining a total score (0-198). Treg frequency was assessed in peripheral blood mononuclear cells by flow cytometry, as the percentage of CD127low FOXP3+ in live CD4+ T cells (%Treg). Results At baseline we identified a median%Tregs of 4.6 (IQR 1.1), inversely correlating with DAS28 (r=-0.5, p=0.02), DAPSA (r=-0.7, p=0.003), CDAI (r=-0.6, p=0.01), SDAI (r=-0.6, p=0.003 and US inflammatory score (r=-0.6, p=0.01) (Figure 1). Treatment with apremilast was able to induce a significant improvement in all activity indices at T1 (DAS28, P=0.009; DAPSA, P=0.01; CDAI, P=0.005; SDAI, P=0.006; US score, P Conclusion The results of our study demonstrate that%Treg is a marker of disease activity in PsA patients. Moreover, the baseline value of Tregs could predict the response to apremilast after 12 weeks of treatment. Reference: [1] Chavele KMet al, FEBS Lett2011. Disclosure of Interests Fulvia Ceccarelli: None declared, Ilenia Pacella: None declared, Ramona Lucchetti: None declared, Arianna Forniti: None declared, francesca spinelli: None declared, enrica cipriano: None declared, Carlo Perricone Speakers bureau: BMS; Lilly, Celgene, Sanofi, Simona Truglia: None declared, Francesca Miranda: None declared, Rossana Scrivo: None declared, cristiano alessandri: None declared, Vincenzo Barnaba: None declared, Guido Valesini: None declared, Silvia Piconese: None declared, fabrizio conti: None declared

Background The introduction of TNF inhibitors have revolutionized the outcome of patients affected by Rheumatoid Arthritis (RA). In the last years, pharmaco-economic implications determined the introduction of biosimilar as alternative to originator biological drugs. Phase I and head-to-head phase III clinical studies demonstrated pharmacokinetic equivalence and comparability in terms of efficacy, safety, immunogenicity and tolerability. However, biosimilar drugs demonstrated some differences related to charge and glycosylation, not influencing the function and the ability to bind the soluble TNF. To date, very few data are available concerning the use of biosimilar drugs in a real-life setting. Results from DANBIO registry suggested a lower retention rate in RA patients switchers from Etanercept originator (ETA) to biosimilar (SB4) versus the historic ETA cohort and higher in comparison with historic SB4 patients (1). Objectives To compare the efficacy of ETA versus SB4 in a cohort of RA patients in a real life setting. Methods In this monocentric case-control prospective study, we consecutively enrolled RA patients starting ETA or SB4 treatment from 2015. RA diagnosis was made according with ACR/EULAR 2010 criteria (2). Data were collected and entered into a standardized, computerized, electronically filled-in form. We included patient demographics, date of diagnosis, comorbidities and previous and concomitant medications. The clinical evaluation included the count of swollen and tender joints and the patient‘s and physician’s global disease assessment based on a visual analogue scale (VAS; range, 0 to 100 mm). Disease activity was measured according to the disease activity score in 28 joints (DAS28ESR) (3). The patients were asked to fill in the Health Assessment Questionnaire (HAQ). All the patients were evaluated at the beginning of treatment (T0) and after 4 (T1) and 12 months (T2). Clinical response to treatment was evaluated by using EULAR criteria (4). Results We evaluated 35 RA patients treated with SB4 (M/F 2/33; median age 63 years, IQR 21; median disease duration 108 months, IQR 138) and 40 with ETA (M/F 5/35; median age 60.5 years, IQR 20; median disease duration 102 months, IQR 141). Biologic drug was prescribed as first-line biological treatment in 71.4% of SB4 cohort and in 80.0% of ETA. At T0 no significant differences were observed among the two groups in terms of DAS28ESR [SB4 median 4.6 (IQR 1.8), ETA 4.3 (IQR 1.9), p=ns] and HAQ [SB4: median 1 (IQR 1.05), ETA median 1 (IQR 0.85), p=ns]. In both groups we observed a significant reduction of DAS28 values at T1 (BS4 p=0.01; ETA p Conclusion The results of our study confirmed in a real-life setting the efficacy of SB4 in RA patients, as demonstrated by the significant reduction of DAS28ESR values after 4 and 12 months of treatment, similarly to ETA. Nonetheless, ETA seems to be able to induce a remission status earlier than SB4. References [1] Glintborg B, et al. Ann Rheum Dis. 2018 [2] Aletaha D, et al. Arthritis Rheum. 2010 [3] Anderson JK, et al. Arthritis Care Res. 2011 [4] van Gestel AM, et al. Arthritis Rheum. 1996 Disclosure of Interests Ramona Lucchetti: None declared, Fulvia Ceccarelli: None declared, Carlo Perricone Speakers bureau: BMS; Lilly, Celgene, Sanofi, Simona Truglia: None declared, Francesca Miranda: None declared, Manuela Di Franco: None declared, Valeria Riccieri: None declared, Rossana Scrivo: None declared, Antonio Sili Scavalli: None declared, francesca spinelli: None declared, cristiano alessandri: None declared, Guido Valesini: None declared, Roberta Priori: None declared, fabrizio conti: None declared

Background: an increased risk of malignancies (1.5-5 times) was found in Systemic Sclerosis (SSc). Well recognized risk factors are the diffuse form, advanced age and (1), more recently, the positivity for anti-RNA Polimerase III antibodies (aRNAP3) has assumed considerable importance (2). Objectives: the aim of this study was to evaluate the frequency of neoplasms and precancerous conditions, as well as the main risk factors, in our cohort of patients with SSc. Methods: we enrolled 312 consecutive patients (288/92% females and 24/8% males, mean age 62.3 years, average disease duration 108 months) afferent at our department from 2000 to 2018, with a diagnosis of SSc confirmed according to the 2013 aCR/EULAR criteria (3). All patients underwent clinical, instrumental and laboratory evaluation. In 93 patients, negative for anti-topoisomerase I antibodies (aScl70) and anti-centromere antibodies (ACA), the presence of aRNAP3 antibodies was evaluated by an ELISA method (QUANTA LiteTM RNA Pol III). Results: we found a limited form of disease in 229 patients (73.4%) and a diffuse form in 83 (26.6%). Eighty eight (28.2%) patients were positive for aScl70, 112 (35.9%) for aCA and 17 (5.4%) for aRNAP3. In the whole group, 44 (14%) patients had a positive familiar history for neoplasm while 105 (33.65%) had a history of neoplasms and/or precancerous conditions. Among these 105 cases, 44 (41.9%) were malignant, 50 (47.6%) benign and 11 (10.5%) had precancerous conditions. The most frequent neoplasms were breast carcinomas (14 cases/14.9%), thyroid (7 cases/7.4%), lung and kidney (3 cases/3.1%), melanomas (5 cases/5.3%). The most frequent precancerous condition was Barrett’s esophagus (7 cases/63.3%). Regarding the antibody profile, 5 (4.8%) patients were positive for anti-RNAP3 and only 2 (1.9%) of these patients presented a malignant neoplasm, breast cancer in both cases. In 30 cases (28.6%) these neoplastic/precancerous conditions had arisen in the close period (± 36 months) at the SSc diagnosis and only 3 of them were anti-RNAP3 positive. Among the evaluated risk factors. Only familiarity was significantly associated with the development of neoplasia (p = 0.003), confirmed at the multivariate analysis (OR 2.9, IC95% [1,5-5,7]; p=0,002). Conclusion: our study evaluated not only malignant neoplasms, but also benign neoplasms and precancerous conditions and identified familiarity as the only significant risk factor. In our cohort we did’nt find any relationship between the presence of anti-RNAP3 antibodies and the development of neoplasms, not even stratifying for the type of neoplasm. However, to better define our data, we should analyze anti-RNAP3 also in the double negative (antiScl70 and aCA) cases, in light of the recent evidence of double antibody positivity, as well as other newly investigated rare autoantibodies, associated with neoplasm in many connective tissue diseases, including SSc. References [1] Szekanecz E, et al. (2012) autoimmun Rev11, 852; [2] Shaha aAet al(2017) J Scleroderma Relat Disord. 2, 153; [3] Van den Hoogen F, et al. (2013) ann Rheum Dis72, 1747–55. Disclosure of interests: Katia Stefanantoni Consultant for: only 1 scientific advice for Italfarmaco in 2016, Natalia Di Tommaso: None declared, Nicoletta Iannace: None declared, Iliana Sciarra: None declared, Carlotta angelelli: None declared, Elena Marafioti: None declared, Greta Pellegrino: None declared, massimiliano vasile: None declared, Guido Valesini: None declared, Valeria Riccieri: None declared

Background: Frailty is a condition characterized by the reduction of the individual’s homeostatic reserves, leading to an increased vulnerability to stressors and an increased risk of unfavourable events. The aging of the population and the consequent need to implement new paradigms of care and assistance, have given this tool a growing interest in many medical disciplines1. In rheumatology, however, the interest is still limited2. The Frailty Index (FI), developed on an arithmetical model of deficit accumulation, is an accurate tool for assessing frailty, providing an estimate of the biological aging. Objectives: Creation of a FI to be used in clinical practice in patients with Sjogren’s syndrome (SS) and evaluation of the correlations with patient‘s age, duration of illness, activity and disease damage at baseline and in the following 5 years. Methods: The FI is composed by a checklist of non-predefined variables (deficits) constituted by symptoms, signs, diseases, disabilities, and laboratory findings. The deficits must meet these criteria: age-related; associated with negative outcomes; multidimensional (referring to different domains of the health status); present in at least 1%, but not more than 80% of the sample. To each variable is assigned the value of 0 (= no deficit) or 1 (= deficit). The FI is the ratio between deficits presented by the individual and the total number of deficits considered, thus providing a measure of frailty ranging between 0 (no frailty) and 1 (maximum of frailty)3. A FI was developed for patients with SS consisting of 43 items (17 comorbidities, 14 signs and symptoms, 5 disabilities and 7 laboratory findings). Statistical analysis was performed with Spearman’s test for correlation assessment, the Mann Whitney test for comparing non-parametric variables was used. Results: FI was administered to a first small group of 30 female consecutive patients recruited as outpatients at the clinic dedicated to SS. The average age was 57.2 yrs, mean age at diagnosis 52.7 yrs and average disease duration 4.7 yrs. At the time of completing the FI, the average disease activity (ESSDAI) was 3.4, the mean value of the damage (SjSDDI) 1.6 and the average score of FI equal to 0.21. A statistically significant correlation between FI and age has been reported (p = 0.017). No significant correlations between frailty and duration, activity and disease damage have been highlighted at the moment. Conclusion: For the first time a FI was developed for patients with SS consisting of 43 items. The data shows a relationship between age andFI. The correlation is statistically significant, similarly to what is reported in the literature for other conditions. This confirms that FI is indeed an objective marker of aging and even though the sample population is young (average age = 57.2 years), FI maintains its main properties. This tool can be used to assess the health status of patients, making it possible to identify those at greater risk of trajectories or unfavourable outcomes. It is currently being administered the FI to patients with SS whose clinical course will be evaluated in the next 5 years (complications, mortality, hospitalization, institutionalization and disability). References [1] Canevelli M, et al, Promoting the Assessment of Frailty in the Clinical Approach to Cognitive Disorders, Front. Aging Neurosc 2017 [2] Rockwood MR, et al, FI to Measure Health Status in People with SSc, J Rheum 2014 [3] Searle SD, et al, A standard procedure for creating a FI, BMC Geriatrics2008 Disclosure of Interests: None declared

Background: Immune checkpoint inhibitors (ICIs) has radically changed the oncology field: the blockade of co-stimulatory molecules on T cells, antigen presenting cells and tumor cells induces unchecked T cell activation with subsequent immune response targeting malignant cells. In the last years, different ICIs have been approved for the treatment of several malignancies. The stimulation of the immune response could be associated with the development of immune-related adverse events (irAEs), potentially involving every organ/system (1). Musculo-skeletal manifestations represent one of the most common irAEs developing during ICIs treatment: up to 40% of treated patients could experience arthralgia or arthritis. Moving from these evidences, the role of the rheumatologist became very important in the management of ICIs treated patients (2). Objectives: To determine the frequency of musculo-skeletal manifestations in patients treated with ICIs in a combined rheumatology/oncology outpatient clinic. Methods: From January 2015 we organised a rheumatology/oncology combined outpatient clinic: all patients starting an ICIs treatment were referred from oncologist to rheumatologist. Data from patients, including demographic features, date of diagnosis, comorbidities and previous and concomitant medications, smoke habit, were collected and registered into a standardized, computerized, electronically filled-in form. All the patients underwent to a physical and laboratory evaluation in order to assess the presence of tender and swollen joints. In case of joint involvement, we assessed disease activity by clinimetric evaluation (DAS28) and ultrasonographic assessment of involved joints (presence of active synovitis as for presence of power Doppler). Moreover, a laboratory evaluation including, ESR, CRP, and autoantibodies (ANA, ACPA, RF) was performed. Results: Seventy-two patients were evaluated (M/F 48/24, median age 66.0 years, IQR 13.0; median disease duration 7 months, IQR 13.0). Concerning malignant disease, 75.1% were affected by non-small cell lung cancer, 15.3% by renal cell carcinoma, 6.9% by melanoma, 2.7% by other malignancies; all patients were treated with anti-PD-1, 67 (93.1%) with nivolumab and 5 (6.9%) with pembrolizumab. During ICIs treatment, 7 patients (9.7%) developed clinically evident synovitis (absolute risk: 0.1; incidence rate 0.01 patients/month): table 1 reports the main features of these 7 patients. According with ACR/EULAR 2010 criteria, two patients could be classified as affected by rheumatoid arthritis (RA). Six patients (85.7%) were treated by prednisone (dosage range 10-12.5mg/daily) or NSAIDs, experiencing a rapid, complete and persistent response. Patient 2, due to resistance to prednisone, was treated by methotrexate 10mg/weekly achieving remission after 6 weeks. Conclusion: The present study represents the first attempt to apply a multidisciplinary approach involving rheumatologists and oncologists in the evaluation of patients treated with ICIs. We found a high absolute risk (10%) to develop synovitis in patients treated by ICIs. Interestingly, the majority of these patients experienced a clinically evident synovitis promptly responding to glucocorticoids and not requiring further DMARDs treatment. This could suggest a peculiar pathogenesis of such ICIs-induced arthritis. References: [1] Calabrese L & Velcheti V, Ann Rheum Diseases 2016; 2. Mooradian MJ et al, Semin Arthritis Rheum 2018 Disclosure of Interests: Fulvia Ceccarelli: None declared, Andrea Botticelli: None declared, Alain Gelibter: None declared, Ilaria Leccese: None declared, Ilaria Zizzari: None declared, Grazia Sirgiovanni: None declared, Francesca Romana Di Pietro: None declared, Ramona Lucchetti: None declared, Carlo Perricone Speakers bureau: BMS; Lilly, Celgene, Sanofi, Enrico Cortesi: None declared, Marianna Nuti: None declared, fabrizio conti: None declared, Paolo Marchetti: None declared, Guido Valesini: None declared

Background Rheumatoid arthritis (RA) is more prevalent in women than men (F:M=4:1), due to hormonal, genetic and environment factors. Women present higher disease activity markers as Disease Activity Score-28 (DAS28) and Health Assessment Questionnaire (HAQ), at the onset and after c-DMARDs therapy, without correlation with radiographic damage. Objectives The purpose of this study was to assess gender differences in RA patients after anti- tumor necrosis factor (TNF) α treatment. Methods Ninety-six patients were enrolled at the beginning of anti-TNF α therapy (etanercept and adalimumab). All patients satisfied 1987 and 2010 ACR criteria for RA. They underwent to clinical and clinimetric evaluation at baseline (T0) and after three (T3) and six (T6) months of therapy with: tender and swollen joints, Visual Analogic Scale (VAS) pain, VAS patient and physician, DAS28, Clinical/Simplified clinical disease activity index (CDAI/SDAI) and HAQ. The evaluation of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Rheumatoid Factor (RF) and anti-citrullinated protein antibody (ACPA) was performed in all patients. Results Among these patients, 70 were women and 26 men; 81 patients (58 female, 23 male) started etanercept and 15 adalimumab (12 female, 3 male). They presented a mean age of 56.4 ± 14.5 years (women 55.2 ± 15.4, men 60 ± 11.2) and mean disease duration of 11 ± 6.8 years (woman 11.51 ± 6.3, men 9.6 ± 8.1). Both women and men had a DAS28 reduction after 3 and 6 months therapy (p Conclusion In this study, both women and men had a good response to anti-TNF treatment but women presented worse clinical response. Female gender resulted the only variable associated with DAS28 reduction differences. We could hypothesize that beyond to biological factors, also social contest, daily life and work activity could explain a worse impact of disease on women. References [1] Neovius M, Ann Rheum Dis 2011; [2] O.L. Quintero, et al., Journal of Autoimmunity 2012. [3] M Ahlm aen, Ann Rheum Dis 2010. [4] Jawaheer, et al, The Journal of Rheumatology 2010. [5] Jawaheer, et al, The Journal of Rheumatology 2012. [6] Arnett FC, Arthritis Rheum 1988. [7] Aletaha D, Arthritis Rheum 2010. Disclosure of Interests None declared

Background Nailfold capillaroscopy (NC) is a simple and non-invasive diagnostic technique, able to investigate microvascular features. In subjects with anti-phospholipid autoantibodies (aPL) many different endothelial abnormalities have been described. Objectives We aimed to investigate the role of NC in aPL positive (aPL+) subjects, highlighting the main microvascular alterations, detected by NC. Methods We enrolled 39 patients with primary anti-phospholipids syndrome (pAPS) (32 females, mean age 43 years, mean disease duration 7 years), 47 patients with secondary anti-phospholipis syndrome (sAPS) due to Systemic Lupus Erythematosus (36 females, mean age 44 years, mean disease duration 15.5 years) and 17 aPL+ subjects without any autoimmune disease, defined as aPL carriers (16 females, mean age 42 years). All subjects underwent clinical and laboratory evaluations as well as NC with both characterization of morfological parameters and attribution of a semiquantitative score. Results The main NC findings were: morphological alterations (tortuous, bushy and/or ramified capillary) in 100% patients with pAPS, in 77% sAPS patients and in 88% aPL carriers; microhaemorragies in 56% pAPS patients, in 49% sAPS patients and 24% aPL carriers; enlarged hairpins in 23%, 41% and 18% subjects with pAPS, sAPS and aPL carriers respectively. In 6.3% sAPS patients, an early scleroderma pattern was detected. A NC semiquantitative score 1 was found in 58.9% pAPS patients, in 57.4% sAPS patients and in 70.5% aPL carriers. Among those cases with abnormal NC findings, we found that a higher NC score (>2) was significantly more frequent in pAPS (21.7%) and sAPS (22.2%) patients respect to aPL carrier cases (8.3%) (p We also found, among the main cardiovascular risk factors, that a higher score (1) was significantly associated with the presence of diabetes mellitus in pAPS patients (p Conclusion Our findings show that some NC aspecific abnormalities are more frequently found in aPL positive subjects, mainly in pAPS and sAPS ones. Altough not specific, such NC features seem to be associated with the presence of vascular risk factors. Thus NC could be regarded as a useful tool in order to evaluate microcirculation in aPL positive cases. References [1] Tavakol MEet al, Biomed Res Int2015; 2015: 974530. [2] Maricq HRet al, Arthritis Rheum1980; 23: 183 – 188. [3] Vaz JLPet al, Rheumatology2004;43:1025–7. [4] Sulli A, J Rheum2000;27:1574–6. [5] Aslanidis S, Clin Exp Rheum2011;29:307–9. Disclosure of Interests massimiliano vasile: None declared, Katia Stefanantoni Consultant for: Only 1 scientific advice for Italfarmaco in 2016, Fulvia Ceccarelli: None declared, Elena Marafioti: None declared, fabrizio conti: None declared, Valeria Riccieri: None declared, Guido Valesini: None declared

Background Women suffering from autoimmune diseases, such as Systemic Lupus Erythematosus (SLE), could develop menopause at a younger age in comparison with healthy population. In particular, a higher frequency of abnormal ovarian function has been described in SLE cohorts1-4. The presence of a cause-effect link between the disease and such modifications remains poorly understood. The role of disease activity and chronic damage, combined with the intake of some drugs, such as cyclophosphamide (CYC), has been suggested2. Objectives We evaluated the age at natural menopause and the prevalence of premature ovarian failure (POF) in a monocentric Caucasian SLE cohort. Additionally, we analyzed the possible association with the disease features. Methods We performed a cross-sectional case-control study, enrolling consecutive SLE women and reporting their clinical and laboratory data. As control group (healthy controls - HC), women without autoimmune diseases were enrolled. By using an interview, gynecological characteristics were investigated in patients and controls: in particular, we registered age at menarche, occurrence and age of menopause, history of hysterectomy. Natural menopause was defined as the absence of menses for at least 12 months in women aged ≥40 years and POF as amenorrhea of at least 12 months in women Results We enrolled 196 Caucasian women with SLE (median age 47.0 years, IQR 16.7; median disease duration 132 months, IQR 180) and 90 HC (median age 49.9 years, IQR 15.0). Ninety-four SLE patients (48.0%) and 26 HC (23.4%) referred a condition of menopause: the median age at occurrence was significantly lower in SLE than HC (47 years, IQR 8.0 versus 50.5 years, IQR 4; P=0.0001). Among the SLE patients, a natural menopause was observed in 70 subjects (74.4%), surgical in 7 (7.4%), iatrogenic in 17 (18.1%). In particular, 13 (13.8%) SLE patients referred the occurrence of menopause after CYC exposure. Excluding SLE patients with surgical menopause, we registered POF in 16 patients (17%); this prevalence was significantly higher in comparison with HC group, in which none of subjects experienced POF (P=0.0001). The comparison between SLE patients developing POF and those with natural menopause history demonstrated a significant higher prevalence of anti-Sm (31.2% versus 10.2%; P=0.0004), anti-RNP (25.0% versus 12.8%; P=0.02), anti-cardiolipin (aCL) IgG/IgM (50.0% versus 26.9%; P=0.0008) and lupus anticoagulant (37.5% versus 17.9%; P=0.002). As expected, a significant more frequent CYC treatment was identified in patients developing POF (56.0% versus 11.0%; P=0.0001). Moreover, POF subjects showed a significant more frequent history of treatment with azathioprine (62.5% versus 30.7; P=0.0001), mycophenolate mofetil (50% versus 20.5%; P=0.0001) and cyclosporine A (37.5% versus 19.2%; P=007). No significant differences were found in terms of clinical manifestations and mean SLICC/ACR damage index (SDI). Conclusion In the present study, we observed a significantly lower age at menopause in SLE patients in comparison with HC; in addition, a significantly higher frequency of POF was observed. POF was associated with a more active disease, in terms of autoantibodies prevalence and use of immunosuppressant drugs. Finally, for the first time, it was found an association between POF and antiphospholipid positivity, suggesting a possible role of these antibodies, in particular aCL, in POF development. References [1] Mayorga J, et al. Lupus 2016 [2] Malheiro, et al. Gynecol Endocrinol 2014 [3] Fatnoon NN, et al. Singapore Med J 2008 [4] Lawrenz, et al. Lupus 2011. Disclosure of Interests Valeria Orefice: None declared, Fulvia Ceccarelli: None declared, Giuseppina Perrone: None declared, Carmelo Pirone: None declared, Carlo Perricone Speakers bureau: BMS; Lilly, Celgene, Sanofi, Simona Truglia: None declared, Francesca Miranda: None declared, viviana antonella pacucci: None declared, francesca spinelli: None declared, Paola Galoppi: None declared, cristiano alessandri: None declared, Guido Valesini: None declared, fabrizio conti: None declared

Career situation of first and presenting author Post-doctoral fellow. Introduction Sjogren’s syndrome (SS) is an autoimmune condition characterised by systemic B cell activation, autoantibody production and ectopic germinal centers (GC) formation within salivary gland (SG). The extent of SG infiltrate has been proposed as biomarker of disease severity. Plasma levels of CXCL13 correlate with GC activity in animal models and disease severity in SS, suggesting its potential use as a surrogate serum marker to monitor local B cell activation. Objectives To evaluate the potential role of CXCL13 as biomarker of SG pathology in two independent SS cohorts. Methods 109 patients with SS were recruited at Sapienza University of Rome (Italy) (n=60), or at Queen Elizabeth Hospital in Birmingham and Barts Health NHS Trust in London (n=49). Both sera and matched paraffin-embedded minor SG biopsy were available. Sicca (n=57) and healthy subjects (HS) (n=19) sera were used as control. CXCL13 gene expression was also assessed in 25 frozen SGs. Results CXCL13 serum levels were higher in SS patients [90.3 (84.2) pg/ml], compared to both sicca [61.9 (38.6) pg/ml), p=0.0005] and HS [36.5 (40.18) pg/ml, p Conclusions Our data foster the use of CXCL13 to monitor the extent of local pathology in SS and its validation in longitudinal clinical studies. Both serum and tissue expression of CXCL13 correlate with SS histological severity, suggesting a major role of this chemokine in SG lymphocytes recruitment and organization. Disclosure of Interest None declared.

Sjogren’s syndrome (SS) is a chronic autoimmune disease characterised by B-cell hyper-activation and exocrine gland infiltration that results in loss of glandular function, systemic manifestations and autoantibody production. The phosphatidylinositol 3–kinase delta isoform (PI3Kδ) belongs to a family of intracellular lipid kinases that regulate metabolism, survival, proliferation, apoptosis, growth, and cell migration and has been successfully targeted in B-cell malignancies. Given the central role of the B-cells in the pathogenesis of SS we investigated evidence for the engagement of the PI3Kδ pathway in SS and the functional consequences of blocking PI3Kδ in an animal model of SS. PI3K pathway activation was investigated in salivary gland (SG) biopsies from patients with SS or non-specific chronic sialoadenitis (NSCS). Samples were stained for phosphorylated ribosomal protein S6 (pS6), a downstream effector in the PI3Kδ pathway. UCB5857, a small molecule inhibitor of PI3Kδ, was used either prophylactically or therapeutically in vivo in an inducible model of ectopic lymphoneogenesis in murine SGs that mimics SS. Flow cytometry, immunofluorescence and quantitative PCR was used on the murine isolated SG to evaluate the samples at peak of inflammation which is day 15 post-cannulation. Histological staining for pS6 showed significant expression of pS6 in SS samples relative to NSCS control, confirming engagement of the PI3K pathway. pS6 was detected within lymphoid aggregates in both T- and B-cell areas and on the periphery of the lymphoid foci in SG biopsies. pS6 staining was predominantly found on CD138 + plasma cells in SG biopsies. Mice treated either prophylactically or therapeutically with UCB5857 displayed decreased lymphocyte infiltration in cannulated salivary glands relative to vehicle treated mice. Additionally, a gene expression profile associated with ectopic lymphoneogenesis (CXCL13, CCL19, CCL21) was significantly impaired in mice treated with UCB5857. Lymphoid aggregates in these mice were characterised by decrease in focus score, smaller size and reduced T/B-cell follicular organisation. Preliminary data implicates activation of PI3Kδ pathway in several cells within the SGs of SS patients that may contribute towards pathology. Accordingly, prophylactic and therapeutic blocking of PI3Kδ results in disaggregation of the inflammatory foci and resolution of SG inflammation in an animal model of SS.

Apremilast, PDE4 competitive inhibitor, has been recently introduced in the treatment of adult psoriatic arthritis (PsA) patients, but only preliminary data are available on imaging evaluation. Thus, we evaluated the response to apremilast in PsA patients by ultrasonographic (US) assessment.Thirty-four patients (M/F 7/27; median age 61 years, IQR 15; median disease duration 10 years, IQR 13) treated for polyarticular involvement were longitudinally evaluated. All the patients were assessed at baseline (T0), and after 6 (T1), 12 (T2), and 24 weeks (T3) by DAS28, CDAI, SDAI, and DAPSA. At the same time-points, US assessment was performed in 22 sites (wrists, MCPs, PIPs): synovial effusion/hypertrophy and power Doppler were scored with a semi-quantitative scale (0-3). A total score, corresponding to patient's inflammatory status, was obtained by their sum (0-198). We assessed also the presence of tenosynovitis of flexorWe found a significant reduction in the US inflammatory score values after 6 weeks (T0, median 15 (IQR 11.2); T1, 6 (10.0); P = 0.0002), confirmed at T2 (4.0 (4.0), P = 0.0002) and T3 (4.0 (6.0); P = 0.0003). Finally, US-detected tenosynovitis was observed in 44.1% of patients: a significant improvement in tenosynovitis score was identified at 6 weeks (T0, median 4 (IQR 4); T1, 1 (2); P 0.0001) and maintained at T2 (0 (IQR 1); P 0.0001) and T3 ((IQR 1.25); P 0.0001).Apremilast is able to induce an early and sustained improvement of ultrasonographic inflammatory status at articular and peri-articular level. Key points •Apremilast induces a significant, early, and sustained improvement of inflammatory joint status in psoriatic arthritis patients. •Ultrasonographic assessment is able to monitor articular and peri-articular response to apremilast.

Association of celiac disease (CD) with systemic autoimmune diseases (ADs) remains controversial. Awareness of CD in these patients is important to prevent complications, including lymphoproliferative disorders. We evaluated previously diagnosed CD prevalence in systemic lupus erythematosus (SLE), primary Sj&ouml, gren&rsquo, s syndrome (pSS) and systemic sclerosis (SSc) patients in comparison to 14,298 matched controls. All patients were screened for subclinical CD. Data from 1458 unselected consecutive SLE (580), pSS (354) and SSc (524) patients were collected. Previously biopsy-proven CD diagnosis and both CD- and AD-specific features were registered. All patients without previous CD were tested for IgA transglutaminase (TG). Anti-endomysium were tested in positive/borderline IgA TG. Duodenal biopsy was performed in IgA TG/endomysium+ to confirm CD. CD prevalence in AD was compared to that observed in 14,298 unselected sex- and age-matched adults who acted as controls. CD was more prevalent in pSS vs controls (6.78% vs 0.64%, p &lt, 0.0001). A trend towards higher prevalence was observed in SLE (1.38%, p = 0.058) and SSc (1.34%, p = 0.096). Higher CD prevalence was observed in diffuse cutaneous SSc (4.5%, p &le, 0.002 vs controls). Subclinical CD was found in two SLE patients and one pSS patient. CD diagnosis usually preceded that of AD. Primary SS and SSc&ndash, CD patients were younger at AD diagnosis in comparison to non-celiac patients. Autoimmune thyroiditis was associated with pSS and CD. CD prevalence is clearly increased in pSS and diffuse SSc in comparison to the general population. The association of CD with diffuse but not limited SSc may suggest different immunopathogenic mechanisms characterizing the two subsets. CD screening may be considered in pSS and diffuse SSc in young patients, particularly at the time of diagnosis.

Objective The reproductive choices of women affected by rheumatic diseases (RD) can be influenced by several factors, including the quality of physician-patient communication. We conducted a survey on reproductive issues aiming at exploring the unmet needs of women with RD during childbearing age. Methods We administered 65 multiple-choice and 12 open-answer questions about pregnancy counselling, contraception, use of drugs during pregnancy and other women reproductive issues to 477 consecutive women with RD aged 18–55 years followed-up in 24 rheumatology centres in Italy. Analysis was restricted to 398 patients who received their diagnosis of RD before the age of 45. According to the RD diagnosis, patients were subdivided into 2 groups: connective tissue diseases (n = 249) and chronic arthritis (n = 149). Results At the time of interview, women in both groups had a mean age of 40 years. Nearly one third of patients in each group declared not to have received any counselling about either pregnancy desire nor contraception. A smaller family size than desired was reported by nearly 37% of patients, because of concerns related to maternal disease in one fourth of the cases. A “Disease Knowledge Index” (DKI) was created to investigate the degree of patients’ information about the implications of their RD on reproductive issues. Having received counselling was associated with higher DKI values and with a positive impact on family planning. Conclusion Italian women of childbearing age affected by RD reported several unmet needs in their knowledge about reproductive issues. Strategies are needed to implement and facilitate physician-patient communication.

Background: Rheumatoid Arthritis (RA) is more prevalent among female individuals. Sex and gender differences may influence disease’s progression and prognosis. To date, the influence of physicians’ gender in the evaluation of RA activity is still largely unknown. Objectives: aim of the study was to investigate a possible discrepancy in the assessment of disease activity in RA patients evaluated by male and female physicians. Further aim was to compare patient and evaluator perceptions about disease activity and global health status. Methods: we enrolled consecutive RA patients. Each patient was separately visited by a female and a male rheumatologist of the same age and training level. Tender (TJ) and swollen joints (SJ) count was performed. Global Health (GH), physician’s (E-VAS) and patient’s (P-VAS) disease activity were reported using a visual analogue scale (VAS 0-100). Both examiners were blinded on ESR and CRP. A third rheumatologist assessed disease activity by DAS28-ESR, CDAI and SDAI. Results: we enrolled 154 patients (122 F, 32 M). GH and P-VAS were significantly higher when collected by the female examiner compared to the male one (respectively, 41,1 ± 24,4 vs 36,1 ± 24,3, p Conclusion: subjective measure of global health status and disease activity (GH, P-VAS) are generally higher when collected by a female examiner compared to a male one, especially among female patients. This gender discrepancy in subjective measures could influence the evaluation of disease activity indices; however, this does not affect the probability of being defined in remission. Overall, patients have a higher perception of disease activity compared to the health care providers, and the agreement between physician and patients is only moderate, with female patients having the worst perception. Female physician tend to be more in agreement with the patients’ judgement of disease activity maybe because of a more emphatic setting established by the female health care provider. Disclosure of Interests: None declared

BackgroundCognitive impairment (CI) in systemic lupus erythematosus (SLE) is a frequent neuropsychiatric manifestation affecting several domains, even in apparently asymptomatic patients. Current research revealed that the typical CI pattern affects frontal-subcortical circuit and thus executive functions. The impairment of non-literal language or pragmatic language (PL), including metaphors, idioms, inferences or irony has been well described in several conditions such as autism disorders, Parkinson's disease, brain injury and even in earlier phases of neurodegenerative processes. Even if PL neuro-anatomy remains controversial, correlation between executive dysfunctions and non-literal language involvement has been reported both in traumatic injury and mild cognitive impairment patients. Nonetheless, no specific study has been performed to evaluate PL impairment in SLE patients so far.ObjectivesWe aimed at assessing the PL domain in a Italian monocentric SLE cohort in comparison to healthy controls, matched to age and education, through a specific battery, the batteria sul linguaggio dell'emisfero destro (BLED). Secondly, we focused attention on possible correlations between CI and clinical and laboratory SLE-related features.MethodsForty adult patients affected by SLE, according to the American College of Rheumatology (ACR) criteria, and thirty healthy subjects were enrolled consecutively in this cross-sectional study. The protocol included complete physical examination, extensive clinical and laboratory data collection (comprehensive of demographics, past medical history, co-morbidities, disease activity, chronic damage evaluation, previous and concomitant treatments) and cognitive assessment for five different domains: memory, attention, pragmatic language, executive and visuospatial functions. Self-reported scale for anxiety and depression were performed to exclude the influence of mood disorders on cognitive dysfunction.ResultsWe studied 40 Caucasian SLE patients [male (M)/ female (F) 3/37; mean±standard deviation (SD) age 45.9±10.1 years, mean±SD disease duration 120.8±81.2 months] and 30 healthy subjects (M/F 9/21; mean±SD age 41.3±13 years). According to the low level of disease activity and damage (mean±SD Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) of 1.3±2.3, mean±SD Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) Damage Index (SDI) of 0.2±0.5), only 30% of patients was on glucocorticoid treatment at the study entry. PL was the most compromised domain in terms of Mean Domain Z scores. As for the Domain Cognitive Dysfunction score, a deficit of PL was observed in 45% of patients and was significantly more prevalent than memory, executive and visuospatial functions impairment (P = 0.0002, P = 0.0002 and PConclusionIn this study we evaluated for the first time PL in SLE patients finding a dysfunction in almost half of patients. The dysfunction of PL was significantly more frequent than the other domains assessed.

Objectives The aim was to determine whether assisted reproductive technologies (ARTs) confer additional risk in rheumatic patients (in terms of disease flare and fetal–maternal complications) and whether, if performed, their efficacy is affected by maternal disease. Methods Sixty infertile rheumatic women undergoing 111 ART cycles were included. Clinical pregnancy rate, live birth rate, maternal disease flares and maternal–fetal complications were recorded. Results One hundred and eleven ART cycles in 60 women were analysed. We reported 46 pregnancies (41.4%), 3 (3.1%) cases of ovarian hyperstimulation syndrome and no cases of thrombosis during stimulation, pregnancy and puerperium. One or more maternal complication was reported in 13 (30.2%) pregnancies, and fetal complications occurred in 11 fetuses (21.1%). The live birth rate was 98%, but we reported three (6%) perinatal deaths in the first days of life. During puerperium, we recorded one (2.5%) post-partum haemorrhage and one (2.5%) articular flare. Conclusion The safety and efficacy of the ARTs, demonstrated in the general population, seems to be confirmed also in rheumatic patients. No evidence was found to advise against their application, and the choice of therapy should be made depending on the patient’s risk profile, irrespective of whether the pregnancy is natural or artificial induced.

Pregnancy requires a special management in women with inflammatory rheumatic diseases (RDs), with the aim of controlling maternal disease activity and avoiding fetal complications. Despite the heterogeneous course of RDs during pregnancy, their impact on pregnancy largely relates to the extent of active inflammation at the time of conception. Therefore, accurate evaluation of disease activity is crucial for the best management of pregnant patients. Nevertheless, there are limitations in using conventional measures of disease activity in pregnancy, as some items included in these instruments can be biased by symptoms or by physiological changes related to pregnancy and the pregnancy itself may influence laboratory parameters used to assess disease activity. This article aims to summarize the current literature about the available instruments to measure disease activity during pregnancy in RDs. Systemic lupus erythematosus is the only disease with instruments that have been modified to account for several adaptations which might interfere with the attribution of signs or symptoms to disease activity during pregnancy. No modified-pregnancy indices exist for women affected by other RDs, but standard indices have been applied to pregnant patients. The current body of knowledge shows that the physiologic changes that occur during pregnancy need to be either adapted from existing instruments or developed to improve the management of pregnant women with RDs. Standardized instruments to assess disease activity during pregnancy would be helpful not only for clinical practice but also for research purposes. info:eu-repo/semantics/publishedVersion

Background: Anakinra (ANA) is an effective treatment choice in patients with adult onset Still’s disease (AOSD). Variables affecting treatment survival include loss of efficacy or adverse events, but also the decision to discontinue treatment after long-term clinical remission. Objectives: Aims of this study were: (i) to assess the drug retention rate (DRR) of ANA during a long-term follow-up looking for any difference related to the line of biologic treatment, the concomitant use of conventional disease modifying anti-rheumatic drugs (cDMARDs) and the different type of AOSD (systemic versus chronic articular); (ii) to identify predictive factors of lack of efficacy, loss of efficacy, and ANA withdrawal owing to long-term remission. Methods: AOSD patients classified according with Yamaguchi criteria and treated with ANA were retrospectively enrolled in 18 Italian tertiary Centers. Demographic, laboratory, clinical and therapeutic data related to the start of ANA (baseline), the 3-month assessment and the last follow-up visit while on ANA treatment were retrospectively collected and statistically analyzed. Results: One hundred and forty-one AOSD patients (48 males, 93 females) treated with ANA for a mean period of 35.96 ± 36.05 months were enrolled. The overall DRR of ANA was 44.6 and 30.5% at the 60- and 120-month assessments, respectively, with no significant differences between: (i) biologic naïve patients and those previously treated with other biologics (log-rank p = 0.97); (ii) monotherapy and concomitant use of cDMARDs (log-rank p = 0.45); (iii) systemic and chronic articular types of AOSD (log-rank p = 0.67). No variables collected at baseline could predict primary inefficacy, while the number of swollen joints at baseline was significantly associated with secondary inefficacy (p = 0.01, OR = 1.194, C.I. 1.043–1.367). The typical AOSD skin rash was negatively related with ANA withdrawal owing to long-term remission (p = 0.03, OR = 0.224, C.I. 0.058–0.863). Conclusion: Long-term DRR of ANA has been found excellent and is not affected by different lines of biologic treatment, concomitant use of cDMARDs, or type of AOSD. The risk of losing ANA efficacy increases along with the number of swollen joints at the start of therapy, while the typical skin rash is a negative predictor of ANA withdrawal related to sustained remission.

Objectives SS is an autoimmune condition characterized by systemic B-cell activation, autoantibody production and ectopic germinal centres’ formation within the salivary gland (SG). The extent of SG infiltrate has been proposed as a biomarker of disease severity. Plasma levels of CXCL13 correlate with germinal centres’ activity in animal models and disease severity in SS, suggesting its potential use as a surrogate serum marker to monitor local B-cell activation. The aim of this study was to evaluate the potential role of CXCL13 as a biomarker of SG pathology in two independent SS cohorts. Methods 109 patients with SS were recruited at Sapienza University of Rome (Italy) (n = 60), or at Queen Elizabeth Hospital in Birmingham and Barts Health NHS Trust in London (n = 49). Both sera and matched minor SG biopsy were available. Sicca (n = 57) and healthy subjects’ (n = 19) sera were used as control. Results CXCL13 serum level was higher in SS patients compared with controls. Correlations between its serum levels and a series of histomorphological parameters, including size of the aggregates and the presence germinal centres', were observed. Conclusion Our data foster the use of CXCL13 to monitor the extent of local pathology in SS and its validation in longitudinal clinical studies.

Infectious sacroiliitis is an infection of the sacroiliac joint, not easy to diagnose because of its non-specific signs, symptoms and laboratory abnormalities. We describe a case of a 16 year-old male with 5 days’ history of fever, abdominal pain, constipation, low-back and left hip pain extended to the left knee associated with sudden inability to walk. In the first place, magnetic resonance imaging (MRI) examination of his sacroiliac joint revealed an enlarged corpuscolated fluid collection near the left iliopsoas muscle, extended to homolateral paravertebral muscles and a little fluid at the left sacroiliac joint. Drainage by aspiration of the iliopsoas abscess was applied; Staphylococcus aureus was found in the aspirated fluid and isolated from the blood too. Therefore intravenous antibiotic therapy was begun. Follow-up MRI exams confirmed the muscle abscess and revealed also a spongy bone edema of the left sacroiliac joint, persisting despite the disappearance of symptoms and the normalization of inflammatory values. It is important to make an early diagnosis of infectious sacroiliitis in order to begin antibiotic therapy as soon as possible, because of the increasing morbidity of infection of sacroiliac joint. In our case MR findings have provided significant orientation towards the final diagnosis of infectious sacroiliitis.

Renal Doppler ultrasound is increasingly used in nephrology for the evaluation of renovascular disease, allograft dysfunction, and chronic nephropathies. We compared intrarenal hemodynamic parameters to biopsy findings of glomerular sclerosis, tubular atrophy, interstitial fibrosis, crescents, arteriolosclerosis, and clinical variables in 100 patients. A positive correlation exists between renal function and percentage of glomerular sclerosis ( P

Background:Thymic stromal lymphopoietin (TSLP) has been implicated in primary Sjögren’s syndrome (pSS) and related B-cell lymphoproliferation/lymphoma (NHL) by tissue studies on salivary glands (SG) (1). It resulted significantly higher in the serum of pSS patients compared to non-pSS sicca and to healthy subjects, with the highest levels found in NHL.Objectives:The purpose of this work was to confirm that serum TSLP is elevated in pSS by the study of independent cohorts.Methods:Serum TSLP levels were measured by ELISA in 91 pSS patients (F=86, 94.5%; mean age 57.2 years, 25-80) from the Udine cohort (cohort 1, UD), Italy. One additional multicentre cohort (cohort 2) from the Italian SS Study Group (GRISS) was studied, including 125 pSS patients from the Universities of Roma (RO), L’Aquila (L’AQ), Pisa (PI) and Perugia (PG). pSS patients with active NHL (n=12 in cohort 1; n=1 in cohort 2) were excluded from comparative analyses to avoid bias. Secondly, additional serum samples from pSS-related NHL in stable and complete remission, from both cohort 1 and 2, were analysed in a separate subgroup (n = 12). Thirdly, a preliminary evaluation of serum TSLP was performed in pSS patients from a different geographical area (University of Athens, Greece; cohort 3).Results:Cohort 2 included 125 pSS patients (F=114, 91.2%; mean age 58.1 years, 23-84): 124 benign, 1 with NHL. In this cohort, serum TSLP levels were confirmed to be high (mean 30.26 pg/mL, 0.41-95.21) and comparable to cohort 1 (mean 33.81 pg/mL, 0-140.8; p=ns). No difference was found by the separate analysis of pSS from each single Centres (RO n=49, mean 33.21, 1.4-95.21; L’AQ n=34, mean 38.6, 16.31-85.11; PI n=28, mean 20.23, 0.41-56.67; PG n=13, mean 19.39, 1.03-68.38; p=ns), and vs cohort 1 (p=ns). The only patient in cohort 2 with NHL showed serum TSLP of 160.91 pg/mL, comparable to the mean TSLP in the 12 UD pSS-NHL (151.96 pg/mL). Importantly, in pSS-related NHL in stable remission, serum TSLP resulted undetectable (7/13) or detectable at very low levels (6/13) (mean 10.46, 0-38.5), and significantly lower than in benign pSS patients from the two cohorts (n=203, mean 31.48, 0-140.8; p=0.0022). Metachronous samples from one patient, at the stage of NHL activity and then at NHL remission, showed a decrease in TSLP from 128.04 pg/mL to undetectable levels. Finally, TSLP levels were increased also in the Greek cohort (mean 54.9, 26.72-78.95), and significantly higher than the two Italian cohorts (p=0.0085 and pConclusion:Serum TSLP levels are increased in pSS, as herein confirmed in independent cohorts. TSLP might be important in the disease pathophysiology and mirrors the course of pSS-related B-cell lymphoproliferation itself. It may thus represent a novel important biomarker.References:[1]Gandolfo S. et al, Clin Exp Rheumatol. 2019 May-Jun;37 Suppl 118(3):55-64.Disclosure of Interests:Saviana Gandolfo: None declared, Cinzia Fabro: None declared, Serena Colafrancesco: None declared, Francesco Carubbi Speakers bureau: Francesco Carubbi received speaker honoraria from Abbvie and Celgene outside this work., Francesco Ferro: None declared, Elena Bartoloni Bocci: None declared, Efstathia Kapsogeorgou: None declared, Andreas Goules: None declared, Luca Quartuccio Consultant of: Abbvie, Bristol, Speakers bureau: Abbvie, Pfizer, Roberta Priori: None declared, Alessia Alunno: None declared, Guido Valesini: None declared, Roberto Giacomelli Grant/research support from: Actelion, Pfizer, Speakers bureau: Abbvie, Roche, Actelion, BMS, MSD, Ely Lilly, SOBI, Pfizer, Roberto Gerli: None declared, Chiara Baldini: None declared, Athanasios Tzioufas: None declared, Salvatore De Vita Consultant of: Roche, Human Genome Science, Glaxo Smith Kline and Novartis

Background:Carbamylation is a post-translational modification occurring under several conditions such as uremia, smoking and chronic inflammation as in rheumatoid arthritis (RA). Low-density lipoproteins (LDL) represent a target of carbamylation. Carbamylated-LDL (cLDL) have an increased inflammatory and atherogenic potential. Growing evidence supports an influence of modified lipids on bone cells homeostasis. However, the role of cLDL on bone cells physiology is still unknown.Objectives:Considering the rate of carbamylation and the role of anti-carbamylated proteins antibodies as markers of erosive disease in RA, the purpose of this study is to investigate the effect of cLDL on bone homeostasis.Methods:In-vitrocarbamylation of LDL was performed as previously described by Ok et al. (Kidney Int. 2005). Briefly, native LDL (nLDL) were treated with potassium cyanate (KOCN) for 4 hours, followed by excessive dialysis for 36 hours to remove KOCN. Both osteoclasts (OCs) and osteoblasts (OBLs) were treated at baseline with 20 μg/ml, 100 μg/ml and 200 μg/ml of cLDL or nLDL. To induce osteoclast differentiation, CD14+ monocytes were isolated from peripheral blood of healthy donors by magnetic microbeads separation and then cultured on a 96-wells plate in DMEM media supplemented with RANKL and M-CSF. After 10 days cells were fixed, stained for tartrate-resistant acid phosphatase (TRAP), a marker of OC differentiation, and counted. OBLs were isolated from bone specimens of 3 patients who had undergone to knee or hip arthroplasty for osteoarthritis and treated for 5 days with different concentrations of cLDL and nLDL. OBLs were fixed and stained for alkaline phosphatase positive activity (ALP), a marker of osteogenic differentiation. Total RNA was extracted from cell lysates. Copies of single-stranded complementary DNA (cDNA) were synthesized and analyzed by real-time PCR to evaluate RANKL and Osteoprotegerin (OPG) mRNA expression levels.Results:In OCLs culture, cLDL significantly decreased the number of OC compared to untreated cells (200 μg/ml p=0,0015) and nLDL treated cells (200 μg/ml p= 0,011; 20 μg/ml p= 0,0014) (Fig 1). Moreover, treatment with cLDL induced an increase of not terminally differentiated OCs, reduced dimensions of OCs, less intense TRAP staining and vacuolization (Fig 2). In OBLs culture, cLDL (20, 100 μg/ml) significantly reduced the ALP activity of OBLs compared with untreated cells (pFig 1.Fig 2.Fig 3.Fig 4.Conclusion:cLDL induce a significant depression of OC and OBL differentiation. Moreover, cLDL increase RANKL expression in OBL, unbalancing bone tissue turnover towards bone resorption. Accordingly, cLDL could be implicated in the bone loss characterizing several conditions associated to an increased carbamylation, such as RADisclosure of Interests:Bruno Lucchino: None declared, Martina Leopizzi: None declared, Tania Colasanti: None declared, Valeria Di Maio: None declared, cristiano alessandri Grant/research support from: Pfizer, Guido Valesini: None declared, fabrizio conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi, Manuela Di Franco: None declared, Francesca Romana Spinelli Grant/research support from: Pfizer, Consultant of: Novartis, Gilead, Lilly, Sanofi, Celgene, Speakers bureau: Lilly