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Objectives Smoking has been connected to citrullination of antigens and formation of anti-citrullinated peptide antibodies (ACPAs) in rheumatoid arthritis (RA). Since smoking can modify proteins by carbamylation (formation of homocitrulline), this study was conducted to investigate these effects on vimentin in animal models and RA. Methods The efficiency of enzymatic carbamylation of vimentin was characterised. B-cell response was investigated after immunisation of rabbits with different vimentin isoforms. Effects of tobacco smoke exposure on carbamylation of vimentin and formation of autoantibodies were analysed in mice. The antibody responses against isoforms of vimentin were characterised with respect to disease duration and smoking status of patients with RA. Results Enzymatic carbamylation of vimentin was efficiently achieved. Subsequent citrullination of vimentin was not disturbed by homocitrullination. Sera from rabbits immunised with carbamylated vimentin (carbVim), in addition to carbVim also recognised human IgG-Fc showing rheumatoid factor-like reactivity. Smoke-exposed mice contained detectable amounts of carbVim and developed a broad immune response against carbamylated antigens. Although the prevalence of anti-carbamylated antibodies in smokers and non-smokers was similar, the titres of carbamylated antibodies were significantly increased in sera of smoking compared with non-smoking RA. CarbVim antibodies were observed independently of ACPAs in early phases of disease and double-positive patients for anti-mutated citrullinated vimentin (MCV) and anti-carbVim antibodies showed an extended epitope recognition pattern towards MCV. Conclusions Carbamylation of vimentin is inducible by cigarette smoke exposure. The polyclonal immune response against modified antigens in patients with RA is not exclusively citrulline-specific and carbamylation of antigens could be involved in the pathogenesis of disease. Trial registration number ISRCTN36745608; EudraCT Number: 2006-003146-41.

ObjectivesRheumatoid arthritis (RA)-specific anti-citrullinated protein/peptide antibodies (ACPAs) might contribute to bone loss and arthralgia before the onset of joint inflammation. We aimed to dissect additional mechanisms by which ACPAs might contribute to development of joint pathology.MethodsFibroblast-like synoviocytes (FLS) were isolated from the synovial membrane of patients with RA. The FLS cultures were stimulated with polyclonal ACPAs (anti-CCP-2 antibodies) purified from the peripheral blood of patients with RA or with monoclonal ACPAs derived from single synovial fluid B cells. We analysed how ACPAs modulate FLS by measuring cell adhesion and mobility as well as cytokine production. Expression of protein arginine deiminase (PAD) enzymes and protein citrullination were analysed by immunofluorescence, and signal transduction was studied using immunoblotting.ResultsChallenge of FLS by starvation-induced stress or by exposure to the chemokine interleukin-8 was essential to sensitise the cells to ACPAs. These challenges led to an increased PAD expression and protein citrullination and an ACPA-mediated induction of FLS migration through a mechanism involving phosphoinositide 3-kinase activation. Inhibition of the PAD enzymes or competition with soluble citrullinated proteins or peptides completely abolished the ACPA-induced FLS migration. Different monoclonal ACPAs triggered distinct cellular effects in either fibroblasts or osteoclasts, suggesting unique roles for individual ACPA clones in disease pathogenesis.ConclusionWe propose that transient synovial insults in the presence of a certain pre-existing ACPA repertoire might result in an ACPA-mediated increase of FLS migration.

Background:Over the past decade, genome wide association studies (GWAS) have identified the JAZF1 locus as a risk locus for several autoimmune diseases, including rheumatoid arthritis (RA)1. However, the exact causal variants in the JAZF1 locus and their underlying regulatory events contributing to RA are still not known. Here, we focus on the effect of these variants on gene expression in synovial fibroblasts (SF).Objectives:To characterize the functional consequences of RA-causal variants in the JAZF1 locus in SF.Methods:Genetic fine-mapping of RA loci was conducted by computing sets of credible variants driving GWAS signals. These credible variant sets were integrated with DNA architecture (ChIP-seq), 3D chromatin interactions (3C, HiC and capture HiC), DNA accessibility (ATAC-seq) and gene expression (RNA-seq and CAGE-seq) datasets to select putative RA-causal variants in SF. Selected variants in the JAZF1 locus were tested for regulatory function by luciferase reporter assays and electrophoretic mobility shift assays (EMSA) in the fibrosarcoma cell line HT1080. The JASPAR2020 database was used to identify putative transcription factors (TF) binding to the selected variants. The expression of HOTTIP was measured by quantitative PCR in hand SF (n=23). Genotyping was done by pyrosequencing.Results:Genetic fine mapping revealed 47 variants in the JAZF1 locus. Integration of these variants with the chromatin datasets prioritized rs2158624, rs57585717 and rs186735625 as the top candidates (posterior probability of causality >0.1) in the JAZF1 locus. We found that rs2158624 and rs186735625 are located in the vicinity of enhancer elements in SF as determined by ATAC-seq. In addition, the region of rs2158624 exhibited strong chromatin interactions with the genomic region of HOTTIP and HOXA13. Both these transcripts were previously shown to be specifically expressed in SF isolated from hands and feet2. Based on this, we selected rs2158624 as the most promising candidate in the JAZF1 locus. We found that the rs2158624-C allele (risk) is associated with lower expression of HOTTIP, but not HOXA13, in hand SF compared to the rs2158624-T allele (non-risk) (p=0.02). Luciferase assays in HT1080 cells demonstrated enhancer activity with both the rs2158624-C allele (p=0.006) and T allele (p=0.04), with no significant difference in enhancer activity between the rs2158624-C and T allele. EMSAs identified stronger specific binding of HT1080-cell nuclear extract for the rs2158624-T allele than for the C allele (risk). Based on the JASPAR2020 database, we identified NFAT5 as a potential TF that can bind to rs2158624 and may regulate the expression of HOTTIP.Conclusion:We were able to substantially narrow down the potential functional variants in the JAZF1 locus using our data integration approach and functional assays. We suggest that the risk allele of rs2158624 influences the binding of TFs controlling the expression of the long non-coding RNA HOTTIP in SF, which might confer specific risk to develop RA in hands.References:[1]Okada Y et al. Genetic of rheumatoid arthritis contributes to biology and drug discovery. Nature 2014;506:376.[2]Frank-Bertoncelj M et al. Epigenetically-driven anatomical diversity of synovial fibroblasts guides joint-specific fibroblast functions. Nat Commun 2017;8:14852.Disclosure of Interests:Miranda Houtman: None declared, Xiangyu Ge: None declared, Amanda McGovern: None declared, Kerstin Klein: None declared, Gisela Orozco: None declared, Mojca Frank Bertoncelj: None declared, Miriam Marks: None declared, Oliver Distler Speakers bureau: Bayer, Boehringer Ingelheim, iQone, Medscape, MSD, Novartis, Pfizer and Roche, Consultant of: Abbvie, Acceleron Pharma, Amgen, AnaMar, Arxx Therapeutics, Bayer, Baecon Discovery, Boehringer, CSL Behring, ChemomAb, Corbus Pharmaceuticals, Galapagos NV, GSK, Glenmark Pharmaceuticals, Horizon Pharmaceuticals, Inventiva, Italfarmaco, iQvia, Kymera, Lilly, Medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Pfizer, Roche, Roivant Sciences, Sanofi and UCB, Grant/research support from: Kymera Therapeutics and Mitsubishi Tanabe, Paul Martin: None declared, Stephen Eyre: None declared, Caroline Ospelt: None declared

Background:The expression of embryonic Homeobox (HOX) genes is tightly regulated based on anatomic location in human adult dermal and synovial fibroblasts. Previously, we showed that HOX-D10,-D11 and -D13 are higher expressed in synovial fibroblasts from small distal joints from the hands and feet, in particular in digits II-V and wrists compared to thumb and that this expression pattern is epigenetically imprinted1. The consequences of the tightly restricted expression of these transcription factors are largely unknown.Objectives:To elucidate the function of HOXD10, -D11 and -D13 in synovial fibroblasts.Methods:Synovial tissues were isolated from paws of naïve C57BL/6 mice (n=8), from patients with rheumatoid arthritis (RA), osteoarthritis (OA) and from healthy controls. Synovial fibroblasts were cultured and transfected with GapmeR to silence HOXD10, -D11, and -D13, respectively or with control GapmeR. RNA sequencing was performed on the NovaSeq platform and pathway analysis was done using R packages and web-based tools (GSEA, EnrichR, Cytoscape). HOXD target gene expression was measured by qPCR (n=3-6).Results:To confirm and further analyze the distinctive expression pattern of HOXD genes, we measured their expression in healthy synovial tissues of different joints of human feet and mouse paws. Similar to what we had found in hands, HOXD10, -D11 and -D13 were less abundant in the joints of the first digit of human feet compared to digits II-V (n=3-4 in each joint). Measurements in joints of mouse paws showed lower expression of HoxD10, -D11 and -D13 in distal interphalangeal joints compared to proximal interphalangeal joints and metacarpophalangeal (MCP) joints, respectively. Silencing of HOXD10, -D11 and –D13, affected the expression of 5333, 2217 and 7347 genes, respectively, in cultured RA synovial fibroblasts from human wrists (n=3).There were more transcripts equally regulated by HOXD10 and -D13 (40% of all HOXD10 and 31% of all HOXD13 regulated transcripts), than by HOXD11 and either -D10 or -D13 (18% of all HOXD10 regulated genes and 16% of all HOXD13 regulated genes), suggesting most redundancy between HOXD10 and -D13 (Figure 1). Among genes differentially expressed in SF isolated from MCP II-V versus thumb joints, 19%, 4% and 33% were regulated by HOXD10, -D11 or –D13, respectively, supporting a role for HOXD13 in particular in shaping the joint specific environment. All three HOXD transcription factors regulated genes involved in cell cycle progression, demonstrating dependence of synovial fibroblasts on these HOX genes for cell division. Other enriched pathways were Toll-like receptor and integrin signaling pathways, regulation of unsaturated fatty acid synthesis and autophagy and extra-cellular matrix protein organization. We could confirm several targets of HOXD10, -D11, and –D13 by qPCR, e.g. NR4A1, ROR2, LIF, ATF3.Figure 1.Comparison of the genes which were differentially expressed after HOXD10-11-13 silencingConclusion:The expression of HOXD10, -D11 and –D13 in synovial fibroblasts and tissues strikinglyoverlaps with predilection sites for RA. Silencing experiments suggested that these embryonic HOX transcription factors have a crucial role in regulating fibroblast functions and might shape a joint specific environment that modulates the development and course of RA in specific joints.References:[1]Klein K, et al. Ann Rheum Dis 2018;77(Suppl 1):P126Disclosure of Interests:Masoumehalsadat Mirrahimi: None declared, Kerstin Klein: None declared, Miranda Houtman: None declared, Malgorzata Maciukiewicz: None declared, Mojca Frank Bertoncelj: None declared, Astrid Juengel: None declared, Martin Berli: None declared, Miriam Marks: None declared, Oliver Distler Speakers bureau:1-Speaker fee on Scleroderma and related complications: Bayer, Boehringer Ingelheim, Medscape, Novartis, Roche• Speaker fee on rheumatology topic other than Scleroderma: MSD, iQone, Novartis, Pfizer, Roche, Consultant of: • Consultancy fee for Scleroderma and its complications: Abbvie, Acceleron Pharma, Amgen, AnaMar, Arxx Therapeutics, Bayer, Baecon Discovery, Boehringer, CSL Behring, ChemomAb, Corbus Pharmaceuticals, Horizon Pharmaceuticals, Galapagos NV, GSK, Glenmark Pharmaceuticals, Inventiva, Italfarmaco, iQvia, Kymera, Medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Roche, Roivant Sciences, Sanofi, UCB• Consultancy fee for rheumatology topic other than Scleroderma: Abbvie, Amgen, Lilly, Pfizer, Grant/research support from:. OD has/had consultancy relationship and/or has received research funding in the area of potential treatments for systemic sclerosis and its complications from (last three years):• Abbvie, Acceleron Pharma, Amgen, AnaMar, Arxx Therapeutics, Baecon Discovery, Blade Therapeutics, Bayer, Boehringer Ingelheim, ChemomAb, Corbus Pharmaceuticals, CSL Behring, Galapagos NV, Glenmark Pharmaceuticals, GSK, Horizon (Curzion) Pharmaceuticals, Inventiva, iQvia, Italfarmaco, iQone, Kymera Therapeutics, Lilly, Medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Novartis, Pfizer, Roche, Sanofi, Serodapharm, Topadur, Target Bioscience and UCB. Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143).• Research Grants to investigate the pathophysiology and potential treatment of Scleroderma and its complications: Kymera Therapeutics, Mitsubishi Tanabe, Caroline Ospelt: None declared

Background:A growing number of professional societies in clinical and medically related disciplines investigate evidence, make recommendations, and take action to advance gender equity. Evidence on women’s advancement and leadership in the context of the European Alliance of Associations for Rheumatology, EULAR, is limited [1].Objectives:The objective of the EULAR Task Force on Gender Equity in Academic Rheumatology was to establish the extent of the unmet need for support of female rheumatologists, health professionals and non-clinical scientists in academic rheumatology and develop a framework to address this through EULAR and Emerging EULAR Network (EMEUNET).Methods:Potential interventions to accelerate gender-equitable career advancement in academic rheumatology were gathered from a narrative review of the relevant literature, expert opinion of a multi-disciplinary Task Force (comprised of 23 members from 11 countries), data from the surveys of EULAR scientific member society leaders, EULAR and EMEUNET members, and EULAR Executive Committee members. These interventions were rated by Task Force members, who ranked each according to perceived priority on a five-point numeric scale from 1 = very low to 5 = very high.Results:A framework of 29 potential interventions was formulated, which covers six thematic areas, namely, EULAR policies, advocacy and communication, EULAR Congress and associated symposia, training courses, mentoring/peer support, and EULAR funding (Figure 1).Figure 1.A framework of potential interventions with the levels of priority, mean and standard deviation (SD)Conclusion:The framework provides structured interventions for accelerating gender-equitable career advancement in academic rheumatology.References:[1]Andreoli L, Ovseiko PV, Hassan N, et al. Gender equity in clinical practice, research and training: Where do we stand in rheumatology? Joint Bone Spine 2019;86(6):669-72.Acknowledgements:The task force is grateful to EULAR for funding this activity under project number EPI 024.Disclosure of Interests:None declared

Background:The coloured altmetrics donut has become a standard feature of online publications. The colours depict different online sources by which an article was mentioned, while the number in the donut, the Altmetric Score (AS), reflects the summarised attention an article has received. The Dimensions database joins citations from any kind of scientific or mainstream publication. Studies analysing the link between the AS and the citation rate of an article suggest that this connection is strongly dependent on the field of research, the type of article and the type of analysis used.Objectives:To analyse the connection between AS and citation rate in articles published in rheumatology journals.Methods:We retrieved data on article usage, AS and citations of articles published in ARD and RMD Open between January 2015 and November 2019. For time-dependent analyses on the influence of AS on citations, articles published in 2019 were excluded. Forward-stepwise regression models were used to explore factors influencing total citation rates. We performed subanalyses, dividing articles in categories of correspondence, original research and editorials/viewpoints. We dichotomised articles by reaching the top 25% in terms of citation count within the first, second, third and fourth year after publication according their category. We explored the risk of reaching these top 25% in dependency of AS using logistic regression (log transformed AS) and receiver operating curve analyses (ROC, reported cut-offs were identified coinciding with 80% specificity).Results:We used 1597 articles published in ARD and 409 articles of RMD Open with complete data on AS and article usage within the mentioned timeframe. AS are higher in more recently published articles (p=0.04, ß: 1.3 per year), but the number of Dimensions citations is lower in more recently published articles (ß: -8.5 per year, p≤0.001). Twitter shows by far the highest activity among the AS subcategories (highly correlating with AS r=0.8, p≤0.001). The total number of twitter mentions increased by 2.8/year from 2015 to 2019, indicating that more recently published articles were more often picked up on twitter. Changes in R2in the regression model indicated that besides time since publication and AS, also the type of article influences citation count. For original research and editorials, AS may significantly add to the variability of the citation count, which was not the case for correspondences. The influence of AS on citation count of editorials added 16% to the 12% variability explained by publication time. Both factors showed similar ß-coefficients (months: ß: 0.76; ß: AS: 0.83). This effect was smaller in original articles (month: ß=0.74; AS: ß=0.11, Total R2: 23.7%). AS significantly coincides with reaching the top 25% of citation counts according to time since publication. For the first year those articles with AS >15 showed a positive Likelihood Ratio (+LR; 95%CI) of 1.6 (1.4-1.9) to reach the top 25%, the second year AS>15: +LR: 1.9 (1.6-2.2), the third year AS>13: +LR 2.3 (1.9-2.7) and in the fourth year AS>12 +LR: 2.1 (1.7-2.7). This effect was again different between publication categories, with no effect of AS in correspondence articles. Figure 1 highlights that AS influences citations of editorials to a larger extent than of original articles, except within the first year of publication.Conclusion:We could show, that Altmetric scores are higher in more recent publications and seem to have an influence on the number of citations, particularly early citations in the first two years after publication. The early implementation of published articles in social media could help to increase overall citation.Acknowledgments:We thank Lindsey Fountain from BMJ for providing citation and usage data.Disclosure of Interests:Paul Studenic Grant/research support from: Abbvie, Caroline Ospelt Consultant of: Consultancy fees from Gilead Sciences.

Background:The heterogeneity of synovial tissues from patients with arthritis could contribute to the interpatient variability in disease course, prognosis and treatment response. Single-cell RNA sequencing (scRNA-seq) permits in-depth analysis of tissue heterogeneity, which could facilitate drug discovery and patient stratification for precision medicine.Objectives:To construct a comprehensive landscape of synovial cell types and molecular pathways in arthritis by integrating our and published scRNA-seq data, generated across different scRNA-seq technologies [Smart-seq2, Drop-seq], cell preparation protocols [dissociated unsorted, sorted cells] and types of arthritis [undifferentiated (UA), rheumatoid arthritis, osteoarthritis].Methods:Synovial tissues were obtained by ultrasound-guided biopsy from patients with UA [not fulfilling the classification criteria for a specific arthritis, n=3]. Biopsies were disintegrated [enzymatic and mechanical disruption] and cell viability assessed with trypan blue. ScRNA-seq libraries [2 per patient] were prepared with 10X Genomics Drop-Seq and sequenced on NovaSeq6000. Bioinformatics analysis of our and published [n=35] datasets1-3was performed using Seurat protocol4with correction for batch effects and filtering low-quality cells. Functional enrichment analysis of marker genes in clusters was done with STRING Protein-Protein networks. Synovitis was assessed with ultrasound and histology.Results:Our tissue disintegration protocol resulted in good cell yield and viability (92%, 72%, 100%). The synovial cellular heterogeneity detected by scRNA-seq reflected the histological findings [Krenn score, pathotype]. These were supported with the ultrasound and clinically assessed disease activity. The integrated analysis of 41 datasets from 38 donors yielded 41845 scRNA-seq cell profiles, 50% contributed by our dataset. An independent analysis of our data and their integration with published data showed that different scRNA-seq methods and protocols can identify all the major synovial cell types and their activation states (Figure 1) with large heterogeneity between donors. We identified a previously undescribed synovial cell population, which was located near the fibroblast cluster, was negative for canonical cell markers, but highly enriched in cell division genes (80% of marker genes). These cells comprised a mixed population of CD34-, podoplanin (PDPN)highor PDPNlowcells that were mostly negative for the sub-lining fibroblast marker THY. Furthermore, they appeared to be highly secretory (extracellular matrix components) and their gene expression profile was inclined towards cell migration, vascular development and insulin growth factor-dependent processes.Figure 1.Heatmap with top 20 cluster gene markers, gene enrichment analysis and UMAP plot of synovial cell clusters.Conclusion:By integrating synovial scRNA-seq data from 41845 cells, we identified a previously undescribed, highly proliferative and secretory synovial cell population in arthritis. We increased the number of known scRNA-seq synovial cell profiles in arthritis by two-fold and demonstrated the robustness of synovial scRNA-seq data outputs across different technologies and protocols. This broadens the current knowledge of synovial tissue heterogeneity and pathology in arthritis.References:[1]Stephenson W. et al. Nat Commun 2017.[2]Mizoguchi F. et al. Nat Commun 2017.[3]Zhang F. et al. Nat Immunol 2018.[4]Stuart T et al. Cell 2019Acknowledgments:This work is supported by Vontobel Foundation and medAlumni University of ZurichDisclosure of Interests:Sam G. Edalat: None declared, Raphael Micheroli: None declared, Tadeja Kuret: None declared, Kristina Buerki: None declared, Chantal Pauli: None declared, Snežna Sodin-Šemrl: None declared, Adrian Ciurea Consultant of: Consulting and/or speaking fees from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Merck Sharp & Dohme, Novartis and Pfizer., Oliver Distler Grant/research support from: Grants/Research support from Actelion, Bayer, Boehringer Ingelheim, Competitive Drug Development International Ltd. and Mitsubishi Tanabe; he also holds the issued Patent on mir-29 for the treatment of systemic sclerosis (US8247389, EP2331143)., Consultant of: Consultancy fees from Actelion, Acceleron Pharma, AnaMar, Bayer, Baecon Discovery, Blade Therapeutics, Boehringer, CSL Behring, Catenion, ChemomAb, Curzion Pharmaceuticals, Ergonex, Galapagos NV, GSK, Glenmark Pharmaceuticals, Inventiva, Italfarmaco, iQvia, medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Roche, Sanofi and UCB, Speakers bureau: Speaker fees from Actelion, Bayer, Boehringer Ingelheim, Medscape, Pfizer and Roche, Caroline Ospelt Consultant of: Consultancy fees from Gilead Sciences., Gregor Rot: None declared, Mojca Frank-Bertoncelj: None declared

Background:Prolonged TNF-induced H3K27 acetylation (H3K27ac) and increased mRNA stability in rheumatoid arthritis (RA) synovial fibroblasts (SF) are leading to a sustained inflammatory response. Underlying enzymes coordinately regulating these pathways have not been identified so far. The histone acetyltransferases cAMP-response element binding protein binding protein (CBP) and p300 are writers of activating H3K27ac marks and close homologues with widely accepted redundant functions.Objectives:To analyze individual functions of CBP and p300 in regulating the inflammatory response of RA SF.Methods:SF were isolated from patients with RA undergoing joint replacement surgery. The expression of CBP and p300 was silenced by transfection of antisense LNA gapmeRs (12.5 nM). SF were stimulated with TNF (10 ng/ml) for 24h. Actinomycin D (10 µg/ml) was added 4h after TNF-treatment for 2h and 4h (n=3) to test mRNA stability. Transcriptomes were determined by RNA-seq (Illumina NovaSeq 6000, n=6). We mapped raw reads from RNA-seq reference genome using STAR. Counts for genes were obtained using Feature counts. We searched for differential expression genes (DEG) across experimental conditions using general linear models (glm) implemented in ‘edgeR’ package of R. Significantly affected genes (± fold change > 1.5, FDR < 0.05, top 3000 genes included) entered pathway enrichment analysis for Gene Ontology (GO) biological process, and KEGG pathways in DAVID. Changes in the mRNA (n=12-14) and protein expression (n=6-12) were confirmed by quantitative Real-time PCR and ELISA. The levels of activating histone marks H3K27ac and nuclear localization of p50 and p65 were analyzed by Western blotting.Results:DEG revealed that silencing of p300 affected the expression of 6026 and 5138 genes in unstimulated and stimulated SF, respectively. In contrast, only 285 and 1911 genes were affected by CBP silencing in unstimulated and stimulated SF, respectively. In TNF-stimulated SF, pathway enrichment analysis of DEG revealed a key role of CBP in regulating the “type I interferon signaling pathway” (p=2.12x10-6). Both, silencing of CBP and p300 regulated genes enriched in the “TNF signaling pathway” (CBP: p=0.005; p300: p=0.031). In contrast to CBP silencing that had anti-inflammatory effects, silencing of p300 had pro-and anti-inflammatory effects. ELISA experiments suggested that silencing of CBP reduced the secretion of IL6 (p-8) being enriched only after silencing of p300.Conclusion:Our results suggested that p300 is the major writer for H3K27ac marks in SF. Additionally, p300 regulated cytokine expression by affecting mRNA stability in a target-specific manner. We identified overlapping and distinct functions for CBP and p300 in regulating the inflammatory response of SF.Disclosure of Interests:Monika Krosel: None declared, Marcel Gabathuler: None declared, Kellie Walker: None declared, Matija Tomsic: None declared, Oliver Distler Grant/research support from: Grants/Research support from Actelion, Bayer, Boehringer Ingelheim, Competitive Drug Development International Ltd. and Mitsubishi Tanabe; he also holds the issued Patent on mir-29 for the treatment of systemic sclerosis (US8247389, EP2331143)., Consultant of: Consultancy fees from Actelion, Acceleron Pharma, AnaMar, Bayer, Baecon Discovery, Blade Therapeutics, Boehringer, CSL Behring, Catenion, ChemomAb, Curzion Pharmaceuticals, Ergonex, Galapagos NV, GSK, Glenmark Pharmaceuticals, Inventiva, Italfarmaco, iQvia, medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Roche, Sanofi and UCB, Speakers bureau: Speaker fees from Actelion, Bayer, Boehringer Ingelheim, Medscape, Pfizer and Roche, Caroline Ospelt Consultant of: Consultancy fees from Gilead Sciences., Kerstin Klein: None declared

Background:Women represent an increasing proportion of the overall rheumatology workforce, but are underrepresented in academic rheumatology, especially in leadership roles [1].Objectives:The EULAR Task Force on Gender Equity in Academic Rheumatology has been convened to establish the extent of the unmet need for support of female rheumatologists, health professionals and non-clinical scientists in academic rheumatology and develop a framework to address this through EULAR and EMEUNET.Methods:To investigate gender equity in academic rheumatology, an anonymous web-based survey was targeted at the membership of EULAR and Emerging EULAR Network (EMEUNET) and their wider networks. The survey was developed based on a narrative literature review [1], best practice from The Association of Women in Rheumatology, a survey of task force members and face-to-face task force discussions. Personal experiences were explored and 24 potential interventions to aid career advancement were ranked. Statistics were descriptive with significance testing for male/female responses compared using chi-squared/t-tests. The level of significance was set at pResults:A total of 301 respondents from 24 countries fully completed the survey. By profession, 290 (86.4%) were rheumatologists, 19 (6.3%) health professionals, and 22 (7.3%) non-clinical scientists. By gender, 217 (72.1%) were women, 83 (27.6%) men, and 1 (0.3%) third gender. By age, 203 (67.5%) were 40 or under. By ethnicity, 30 (10.0%) identified themselves as ethnic minority. A high proportion of respondents reported having experienced gender discrimination (47.2% total: 58.1% for women and 18.1% for men) and sexual harassment (26.2%: 31.8% and 10.8% respectively) (Figure 1). Chi-squared tests on the numbers on which these proportions were based showed statistically significant differences between women and men in having experienced gender discrimination (Χ2=36.959 (df=1), p Figure 1.Perceived gender discrimination and sexual harassment, 301 responsesFigure 2.Mean perceived utility of potential interventions for career advancement by gender and statistically significant gender differences (pConclusion:The results of the survey will inform the development of task force policy proposals for interventions to support career advancement among EULAR and EMEUNET members. The identified interventions have potential to support career advancement of all rheumatologists, health professionals and non-clinical scientists regardless of gender.References:[1]Andreoli L, Ovseiko PV, Hassan N, Kiltz U, van Mens L, Gossec L, et al. Gender equity in clinical practice, research and training: Where do we stand in rheumatology? Joint, Bone, Spine: Revue du Rhumatisme. 2019;86(6):669-672.Acknowledgments:We gratefully acknowledge the rheumatologists, health professionals and non-clinical scientists who responded to the survey.Disclosure of Interests:Pavel V Ovseiko: None declared, Laure Gossec Grant/research support from: Lilly, Mylan, Pfizer, Sandoz, Consultant of: AbbVie, Amgen, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sandoz, Sanofi-Aventis, UCB, Laura Andreoli: None declared, Uta Kiltz Grant/research support from: AbbVie, Amgen, Biogen, Novartis, Pfizer, Consultant of: AbbVie, Biocad, Eli Lilly and Company, Grünenthal, Janssen, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, MSD, Novartis, Pfizer, Roche, UCB, Leonieke van Mens: None declared, Neelam Hassan: None declared, Marike van der Leeden: None declared, Heidi J Siddle: None declared, Alessia Alunno: None declared, Iain McInnes Grant/research support from: Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, and UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, Novartis, Pfizer, and UCB, Nemanja Damjanov Grant/research support from: from AbbVie, Pfizer, and Roche, Consultant of: AbbVie, Gedeon Richter, Merck, Novartis, Pfizer, and Roche, Speakers bureau: AbbVie, Gedeon Richter, Merck, Novartis, Pfizer, and Roche, Florence Apparailly: None declared, Caroline Ospelt Consultant of: Consultancy fees from Gilead Sciences., Irene van der Horst-Bruinsma Grant/research support from: AbbVie, Novartis, Eli Lilly, Bristol-Myers Squibb, MSD, Pfizer, UCB Pharma, Consultant of: AbbVie, Novartis, Eli Lilly, Bristol-Myers Squibb, MSD, Pfizer, UCB Pharma, Elena Nikiphorou: None declared, Katie Druce Speakers bureau: Pfizer and Lilly, Zoltán Szekanecz Grant/research support from: Pfizer, UCB, Consultant of: Sanofi, MSD, Abbvie, Pfizer, Roche, Novertis, Lilly, Gedeon Richter, Amgen, Alexandre Sepriano: None declared, Tadej Avcin: None declared, George Bertsias Grant/research support from: GSK, Consultant of: Novartis, Georg Schett Speakers bureau: AbbVie, BMS, Celgene, Janssen, Eli Lilly, Novartis, Roche and UCB, Anne Maree Keenan: None declared, Laura C Coates: None declared

Background:Long non-coding (lnc-)RNA are regulatory molecules transcribed from DNA similar to mRNA and interact directly with DNA, RNA and proteins. Some lncRNAs have been shown to contain micro (mi-)RNAs in their sequence that can be released by splicing and lead to active miRNA molecules, e.g. lncRNA H19 includes two miRNAs 675-3p and -5p in its sequence.Adipose tissue derived factors (adipokines) are involved in inflammation processes and osteoarthritis (OA) development. The proinflammatory adipokine visfatin has been shown to alter osteogenic differentiation (OD) of pluripotent mesenchymal stem cells (MSCs) and reduces elastic fiber expression, increases matrix mineralization and proinflammatory cytokine and chemokine production(1).Objectives:We evaluated a novel effect of visfatin on lncRNA H19 in MSCs during OD. The goal was to explore the kinetics of the visfatin effect during OD with regard to H19 regulation and to investigate H19 downstream mechanisms leading to the observed altered MSC differentiation and osteoblast activity.Methods:MSCs isolated from OA hip or knee bone (phMSC) and commercially obtained healthy human (h-)MSCs were differentiated towards osteoblasts with/without visfatin, resistin, leptin, TNF and Wnt/TGFβ1 pathway inhibitors. Supernatants were collected at days 2, 7, 9, 14 and 21 of OD, cell lysates at day 2, 7, 9, 14 and matrix mineralization assays conducted at day 21. H19 and miRNA expression was evaluated by real-time PCR after mi-/RNA isolation. IL-6 was analyzed by ELISA.Results:H19 was continuously upregulated in unstimulated controls as expected during OD but also when stimulated with other adipokines. In contrast, stimulation with visfatin significantly decreased H19 (day 2 to 14 of OD, hip-phMSCs: p = 0.0097, knee-phMSCs: p=0.0075, h-MSC: p = 0.044). Visfatin increased matrix mineralization and IL-6 production as expected (hMSC: p = 0.03, phMSC: p = 0.013)(1). TNF stimulation during OD did not lead to a downregulation of H19 nor increased matrix mineralization, thus showing that the effects were visfatin-dependent. H19s endogenous miRNA 675-5p was changed in parallel with H19, increased during control OD and significantly down-regulated by visfatin (e.g. day 14 p = 0.015). However, H19s endogenous miRNA 675-3p was inversely regulated, downregulated during control OD while visfatin stimulation attenuated this effect (e.g. day 14 p = 0.025). Altered Wnt-signaling and involvement of the TGFβ1 pathway could not be observed.Conclusion:H19 is upregulated during OD and may therefore play a regulatory role in the process of osteogenesis. Visfatin stimulation of MSCs during OD showed pro-inflammatory effects, increased matrix mineralization while reducing elastic fiber production(1). These effects were associated with a downregulation of H19, a specific visfatin effect not triggered by other adipokines or TNF. The H19 sequence includes two endogenous micro-RNAs 675-3p and 5p. We demonstrated miRNA 675-5p to be regulated in parallel to H19, whereas miRNA 675-3p was inversely regulated and increased continuously upon visfatin stimulation. Based on these results, we hypothesize that visfatin provides a specific stimulus for the splicing of miRNA 675-3p from H19, in turn leading to H19 reduction. miRNA 675-3p thus represents an effector mechanism of visfatin that contributes to the observed functional effects in differentiating MSCs.References:[1]Tsiklauri, L.et al.Visfatin alters the cytokine and matrix-degrading enzyme profile during osteogenic and adipogenic MSC differentiation.Osteoarthr. Cartil.26, 1225–1235 (2018).Disclosure of Interests:Dennis Küppers: None declared, Lali Tsiklauri: None declared, Marie Hülser: None declared, Klaus Frommer: None declared, Stefan Rehart: None declared, Caroline Ospelt Consultant of: Consultancy fees from Gilead Sciences., Ulf Müller-Ladner Speakers bureau: Biogen, Elena Neumann: None declared

Background:Up to now, three groups used single cell RNA sequencing (scRNA-seq) to analyse the synovium in arthritis using different methods and material to measure RNA expression on a single cell level: Ref. 1 used unsorted dissociated synovial cells and a droplet based method; Refs 2 and 3 performed scRNA-seq on sorted cell populations.Objectives:The aim of this study was to perform a meta-analysis of scRNA-seq data of the synovium in arthritis: 1) to define synovial fibroblast (SF) phenotypes, 2) to confirm differences across SF clusters between rheumatoid arthritis (RA) and osteoarthritis (OA) and 3) to analyse joint specific differences between SF phenotypes.Methods:In addition to the available count matrices [1-3], we used unsorted dissociated synovial cells from three patients with undifferentiated arthritis (UA) with a droplet-based method (10x Genomics). We followed a standard protocol [4] to integrate the datasets into a shared space, even in the presence of extensive technical and/or biological differences (“batch-corrected”). SF were selected as previously described (PDPN+,ISLR+,COL1A2+,PTPRC-) [1-3]. We used a minimum log2 FC of 0.25 for average expression of genes in a cluster relative to the average expression in all other clusters combined to define marker genes. R with Seurat, Monocle and clusterProfiler packages were used for scRNA-seq analysis, pseudotime trajectory analysis and pathway enrichement analysis, respectively. Quantitative PCR (qPCR) (n=6-14 per location and disease), immunohistochemistry (IHC) and Krenn synovitis score (n=5-15 per location and disease) were performed according to standard protocols.Results:Data from 29 RA, 3 UA and 6 OA patients were analysed. From a total of 29’448 cells, we identified 14’787 (50%) with a fibroblast phenotype. Of those, we determined 5 subpopulations (Fig. 1): 1)THY1-CD55hifibroblasts with high expression ofMMP1andMMP3(SF1), 2)THY1loCD34+fibroblasts expressing high levels ofPI16(SF2) 3)THY1hifibroblasts expressing high levels of periostin (POSTN) and collagens (e.g.COL1A1, COL3A1) (SF3), 4)THY1hifibroblasts expressingCXCL12(SF4) and 5)THY1lofibroblasts expressingCXCL12,NR4A1andCCL2(SF5). Fig. 2 shows pathway enrichment map of all marker genes; it organizes enriched terms into a network with edges connecting overlapping gene sets. Pseudotime trajectory axis derived from Monocle indicated that SF4 represent a state between SF3 and SF5. Pseudotemporal expression dynamics ofTHY1marked the progression of these three subtypes (Graph 1). SF1 and SF2 were proportionally underrepresented and SF3-5 overrepresented in RA (chi-squared = 37.18, p = 1.65e-07). The expression of POSTN, a signature gene of SF3, was not different between RA and OA tissues, but significantly correlated with the synovitis score (Spearman ρ = 0.55, p=0.02), in particular with pathological changes in the sublining. POSTN expression was higher in hand than in knee synovial tissues (mean ± SD IHC score: hand 8 ±2, knee 5 ±2) and in cultured SF (qPCR: 10-fold difference). Accordingly, SF3 was enriched in hand versus knee synovial tissues in the scRNA-seq dataset (chi-squared = 944.87, p < 2.2e-16).Fig. 1Fig. 2Graph 1Conclusion:In our meta-analysis, we found comparable subtypes of fibroblasts as in the individual analyses [1-3], showing the robustness of cell phenotype identification using scRNA-seq. The different SF phenotypes appear to be plastic cell states rather than fixed cell subtypes, whose development is controlled by an interrelation between pathological changes in the synovium and joint location.References:[1]Stephenson et al. Nat. Commun. 2018[2]Mizoguchi et al. Nat. Commun. 2018[3]Zhang et al. Nat Immunol. 2019[4]Stuart, Butler, et al. Cell 2019Disclosure of Interests:Raphael Micheroli: None declared, Mojca Frank-Bertoncelj: None declared, Sam G. Edalat: None declared, Kerstin Klein: None declared, Tadeja Kuret: None declared, Kristina Buerki: None declared, Adrian Ciurea Consultant of: Consulting and/or speaking fees from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Merck Sharp & Dohme, Novartis and Pfizer., Oliver Distler Grant/research support from: Grants/Research support from Actelion, Bayer, Boehringer Ingelheim, Competitive Drug Development International Ltd. and Mitsubishi Tanabe; he also holds the issued Patent on mir-29 for the treatment of systemic sclerosis (US8247389, EP2331143)., Consultant of: Consultancy fees from Actelion, Acceleron Pharma, AnaMar, Bayer, Baecon Discovery, Blade Therapeutics, Boehringer, CSL Behring, Catenion, ChemomAb, Curzion Pharmaceuticals, Ergonex, Galapagos NV, GSK, Glenmark Pharmaceuticals, Inventiva, Italfarmaco, iQvia, medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Roche, Sanofi and UCB, Speakers bureau: Speaker fees from Actelion, Bayer, Boehringer Ingelheim, Medscape, Pfizer and Roche, Caroline Ospelt Consultant of: Consultancy fees from Gilead Sciences.

Objective To investigate the effects of BET bromodomain protein inhibition on inflammatory activation and functional properties of rheumatoid arthritis synovial fibroblasts (RASF). Methods The expression of the BET bromodomain proteins BRD2, BRD3 and BRD4 was analysed in synovial tissue by immunohistochemistry. RASE were stimulated with tumour necrosis factor (TNF)-alpha, interleukin (IL)-1 beta and toll-like receptor (TLR) ligands (Pam3, pIC and lipopolysaccharide (LPS)) in the presence or absence of the BET inhibitor I-BET151, or siRNA targeting BRD2, BRD3 and BRD4. RASF expression of inflammatory mediators, including MMP1, MMP3, IL-6 and IL-8, was measured by q-PCR, q-PCR array and ELISA. Cellular viability, apoptosis, proliferation and chemoattractive properties of RASF were investigated using MTT, cell apoptosis ELISA, BrdU-based proliferation and transwell migration assays. Results BRD2, BRD3 and BRD4 proteins were detected in rheumatoid arthritis (RA) synovial tissue, expressed in both RASF and macrophages. I-BET151 suppressed cytokine and TLR ligand-induced secretion of MMP1, MMP3, IL-6 and IL-8, and mRNA expression of more than 70% of genes induced by TNF-alpha and IL-1 beta. Combined silencing of BRD2, BRD3 and BRD4 significantly reduced cytokine and TLR ligand-induced expression of a subset of gene products targeted by I-BET151, including MMP1, CXCL10 and CXCL11. I-BET151 treatment of RASF reduced RASF proliferation, and the chemotactic potential for peripheral blood leucocytes of RASF conditioned medium. Conclusions Inhibition of BET family proteins suppresses the inflammatory, matrix-degrading, proliferative and chemoattractive properties of RASF and suggests a therapeutic potential in the targeting of epigenetic reader proteins in RA

Objective Fibrin deposits are characteristic of the synovial tissues in rheumatoid arthritis (RA). Once citrullinated, fibrin becomes an autoantigen and is thought to contribute in this way to perpetuate the disease. Our study aimed to analyse the responses of RA synovial fibroblasts (RASF) to native and citrullinated fibrin. Methods The transcriptome induced by fibrin in RASF was approached with whole-genome-based gene expression arrays. The upregulation of selected pro-inflammatory genes by fibrin was confirmed in additional primary cell cultures using quantitative PCR and ELISA. Citrullination reactions were carried out with recombinant human peptidylarginine deiminases (PAD) 2 and 4. Results In the whole-genome array native fibrin was found to modulate the gene expression profile of RASF, particularly upregulating mRNA levels of several pro-inflammatory cytokines. The induction of interleukin (IL)-6 and IL-8 by fibrin was confirmed in additional samples at both the mRNA and the protein level. Blocking and knockdown experiments showed the participation of toll-like receptor (TLR)4 in the induction of both cytokines. As compared with the native macromolecule, PAD2-citrullinated fibrin induced significantly higher expression of the pro-inflammatory cytokines in these cells. Conclusions Our results suggest that fibrin mediates inflammatory responses in RASF via a TLR4 pathway. In this way, fibrin and particularly its citrullinated form may contribute to sustain the cytokine burst in RA.

Objective To identify novel microRNA (miR) associations in synovial fibroblasts (SF), by performing miR expression profiling on cells isolated from the human tumour necrosis factor (TNF) transgenic mouse model (TghuTNF, Tg197) and patients biopsies. Methods miR expression in SF from TghuTNF and wild-type (WT) control mice were determined by miR deep sequencing (miR-seq) and the arthritic profile was established by pairwise comparisons. Quantitative PCR analysis was utilised for profile validation, miR and gene quantitation in patient SF. Dysregulated miR target genes and pathways were predicted via bioinformatic algorithms and validated using gain-of-function coupled with reporter assay experiments. Results miR-seq demonstrated that TghuTNF-SF exhibit a distinct pathogenic profile with 22 significantly upregulated and 30 significantly downregulated miR. Validation assays confirmed the dysregulation of miR-223, miR-146a and miR-155 previously associated with human rheumatoid arthritis (RA) pathology, as well as that of miR-221/222 and miR-323-3p. Notably, the latter were also found significantly upregulated in patient RA SF, suggesting for the first time their association with RA pathology. Bioinformatic analysis suggested Wnt/cadherin signalling as a putative pathway target. miR-323-3p overexpression was shown to enhance Wnt pathway activation and decrease the levels of its predicted target β-transducin repeat containing, an inhibitor of β-catenin. Conclusions Using miR-seq-based profiling in SF from the TghuTNF mouse model and validations in RA patient biopsies, the authors identified miR-221/222 and miR-323-3p as novel dysregulated miR in RA SF. Furthermore, the authors show that miR-323-3p is a positive regulator of WNT/cadherin signalling in RA SF suggesting its potential pathogenic involvement and future use as a therapeutic target in RA.

ObjectiveTo analyse the expression of SIRT1 in synovial tissues and cells of patients with rheumatoid arthritis (RA) and to study the function of SIRT1 in inflammation and apoptosis in RA.MethodsLevels of SIRT1 expression were analysed in synovial tissues and cells from patients with RA by real-time PCR and western blotting before and after stimulation with toll-like receptor ligands, tumour necrosis factor α (TNFα) and interleukin 1β (IL-1β). Immunohistochemistry was used to study the localisation of SIRT1. Fluorescence activated cell sorting analysis was performed to investigate the effect of SIRT1 on apoptosis. Peripheral blood monocytes and rheumatoid arthritis synovial fibroblasts (RASFs) were transfected with wild-type or enzymatically inactive SIRT1 expression vectors or with siRNA targeting SIRT1. Cytokine analysis of IL-6, IL-8 and TNFα were performed by ELISA to study the role of SIRT1 on proinflammatory mediators of RA.ResultsSIRT1 was found to be constitutively upregulated in synovial tissues and cells from patients with RA compared to osteoarthritis. TNFα stimulation of RASFs and monocytes resulted in further induced expression levels of SIRT1. Silencing of SIRT1 promoted apoptosis in RASFs, whereas SIRT1 overexpression protected cells from apoptosis. Inhibition of SIRT1 enzymatic activity by inhibitors, siRNA and overexpression of an enzymatically inactive form of SIRT1 reduced lipopolysaccharide-induced levels of TNFα in monocytes. Similarly, knockdown of SIRT1 resulted in a reduction of proinflammatory IL-6 and IL-8 in RASFs.ConclusionThe TNFα-induced overexpression of SIRT1 in RA synovial cells contributes to chronic inflammation by promoting proinflammatory cytokine production and inhibiting apoptosis.

Background Synovial fibroblasts (SFs) contribute to rheumatoid arthritis (RA) pathogenesis by growing into the synovial space and by producing pro-angiogenic and tissue remodelling factors, chemokines and inflammatory cytokines that recruit and stimulate various immune cells. We have recently demonstrated that anti-citrullinated proteins antibodies (ACPAs) promote osteoclast development. In the present work we investigated whether ACPAs can also modulate SFs. Methods SFs were isolated from synovial tissue of RA patients by enzymatic digestion. Polyclonal ACPA and others non-ACPA IgGs were separated from plasma of RA patients by affinity purification on cyclic citrullinated peptide (CCP)-2 column. Monoclonal ACPAs were generated from synovial B-cells. Antibodies were tested in scratch-assays for SF migration and the results were evaluated by NIH ImageJ software. SF adhesion was analyzed by xCELLigence System Real-Time Cell Analyzer (ACEA bioscience). ACPA-induced signalling pathways were examined using inhibitors of phosphoinositide 3-kinase (PI3K), phosphatase and tensin homolog (PTEN), G-protein coupled receptors, focal adhesion kinase (FAK) and peptidylarginine deiminases (PAD) in the migration assays. Protein phosphorylations were monitored by western blot. Results Polyclonal ACPAs but not others IgGs induced both SFs migration (a fold increase of 2.6±0.5, mean±SD, p Conclusions ACPAs promote SFs migration and adhesion acting synergistically with IL-8 through a PAD-dependent pathway. Our findings suggest that SFs may have a potential role in the ACPA-dependent disease propagation from the bone marrow to synovial tissue. Disclosure of Interest None declared

Background and objectives We have recently demonstrated that anti-citrullinated proteins antibodies (ACPAs) promote IL-8 production and osteoclast activation. In a second step this might lead to chronic synovial inflammation characterised by activation of resident synovial fibroblasts (SF). We aimed to investigate the effect of ACPAs and IL-8 on SF. Methods and materials SFs were isolated from synovial tissue of RA patients by enzymatic digestion. Polyclonal ACPA and other non-ACPA IgGs were separated from plasma of RA patients by affinity purification on a CCP2 column. Monoclonal ACPAs were generated from synovial fluid single B-cells. Antibodies were tested in migration scratch assays and evaluated by NIH ImageJ software to calculate the migration index in the presence or absence of exogenous IL-8. SF adhesion was analysed by xCELLigence System Real-Time Cell Analyzer (ACEA bioscience). Impedance-based signals were monitored continuously during 36 h. Blocking experiments using phosphoinositide 3-kinase (PI3K), G-protein coupled receptors or focal adhesion kinase (FAK) inhibitors as well as a pan-peptidylarginine deiminases (PAD) inhibitor were performed in the migration scratch assays in the presence or absence of the antibodies. Phosphorylation signal pathways were detected by western blot. Results Polyclonal ACPAs but not other IgGs induced both SFs migration (a fold increase of 2.6 ± 0.5, mean±SD, p Conclusion ACPAs increase SFs migration and adhesion acting synergistically with IL-8. Our findings suggest that SF might be important players in the ACPA-dependent disease propagation from the bone marrow to synovial tissue.

Background The use of social media (SM) platforms and networks is fast expanding yet their impact especially within the professional world is often under-appreciated and has not been systematically evaluated. Objectives To perform an online survey on the use, perceptions and impact of SM within the rheumatology professional world and beyond. Methods A questionnaire prepared by rheumatologists from different countries within the EMEUNET group was designed to assess perceptions and the impact of SM among users and non-users. EMEUNET is a Europe-wide network of more than 1000 young rheumatologists addressing educational needs and promoting research interests. The survey covered a range of questions from basic demographic information to perceptions on the use and impact of SM in a professional or other. The survey was advertised via three main routes: Twitter, Facebook and by direct email to EMEUNET members. Results 233 anonymized responses were collected from 47 countries. The majority completed the survey via email (90%), the rest via Tw (6%) and FB (4%). 72% of responders were within the age group of 30-39 years. 66% were female; 51% were in a combined clinical/academic job setting. 83% were active users of at least one SM platform with a mean weekly use of 7 hrs, and 71% of those used SM in a work-related manner. The majority used SM for communicating with friends/colleagues (79%), news updates (76%), entertainment (69%), rheumatology clinical (50%) and research (48%) updates. Table 1 shows SM sites and the frequency of use. FB was the dominant SM platform with 91% using it although only 68% professionally, whereas LinkedIn was the dominant platform for professional-related communication. The latter included using SM as a source of information (81%); expanding professional networks (76%); new resources (59%); learning new skills (47%) and establishing a professional online presence (46%). Work-related SM users had a significantly increased use of SM (8 hrs weekly) of which 5 hours were work-related. The main obstacles for not using SM in a work-related manner were “lack of knowledge on how to do so” (44%) followed by “not suitable for individual needs” (30%). 9% were concerned regarding negative impact on their reputation. 68% felt that SM is a safe way of communicating with other people although of those not using SM 37% expressed concerns regarding its safety, exposure of private life and being a time-consuming process. 30% of non-SM users justified not using SM due to lack of knowledge; 26% considered SM unsuitable for their needs and 41% expressed no interest in SM. Conclusions The results highlight that use of SM within rheumatology professionals and basic scientists is considerable, for social but mostly professional reasons. SM provides a good source of information for educational purposes and potential for networking. he lack of knowledge on how to use SM in a work related manner highlights the need for providing resources necessary to enable more widespread use of SM. Despite concerns regarding the safety of SM and exposure of private life, the majority of respondents had a positive view towards SM. Acknowledgements We thank Dr David O9Reilly for his contribution. Disclosure of Interest None declared

We very much appreciate the interest of Drs Cates and Hutchinson1 in our study and absolutely agree that analysing the role of …

Background Education and training related to rheumatic and musculoskeletal diseases are one of the key strategic areas of EULAR. To better understand the educational needs of young clinicians and/or researchers in rheumatology, the Emerging EULAR Network (EMEUNET) and the EULAR Standing Committee on Education and Training (ESCET) developed an educational survey. Methods Students, clinicians and/or researchers below the age of 40 who work in the field of rheumatology were invited to participate in an online-based survey. Invitations were sent to 763 EMEUNET members and young individuals of national organizations. The current abstract presents an interim analysis. Results 458 participants completed the survey. The majority of participants were between 31 and 35 years old (43%), female (66%) and from Europe (91%). Spain (18%), but also the UK, Czech Republic and Portugal (all around 8%) were very well represented. Most participants were trainees in rheumatology (46%) or served as junior faculty (33%). Participants spent a mean of 59% of their time in clinical work and 26% in research, but little in educational and administrative work. While participants mainly performed clinical and/or epidemiological research (63%), scientific foci as defined by ARD key-words varied greatly. Asked for career plans, around 78% of participants intended to work in academia or hospital settings with a lower interest in industry or private practice. A central goal of the survey was to assess the awareness and acceptance of existing EULAR educational opportunities. While 78% of participants were familiar with the role of EMEUNET, relatively little was known about ESCET. Of note, the current EULAR educational portfolio covered well the needs of more than 70% of participants. The various EULAR online courses and the EULAR postgraduate course received the highest ratings considering past participations or current interest. In detail, 28% and 12% of responders had already participated in the EULAR online course on rheumatic diseases and in the EULAR postgraduate course, respectively. Limited funding, either through personal means (58%) or through the home institution (45%), was considered the major obstacle to participate in existing programs. The second major objective of the survey was to determine the educational needs and preferences of young clinicians and researchers in the field. Clinically, more than 90% of participants were interested in receiving training in imaging techniques as well as in general disease review courses. Regarding scientific training, more than 80% of participants were interested in acquiring statistics, presentation, writing and/or reviewing skills. Participants gave very diverse answers regarding preferred learning modalities: most individuals favored live courses or online learning tools over textbooks and lectures as well as case-oriented over systematic learning. Conclusions The EMEUNET/ESCET educational survey was very well-received among young individuals in the field or rheumatology with excellent participation. While the current EULAR educational portfolio is well appreciated, lack of funding may limit the access to it. This new data will help EULAR to adapt their educational portfolio to the needs of young clinicians and researchers. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3015