scholarly journals Differential inflammation-mediated function of prokineticin 2 in the synovial fibroblasts of patients with rheumatoid arthritis compared to osteoarthritis

2021 ◽  
Author(s):  
Kentaro Noda ◽  
Bianca Dufner ◽  
Haruyasu Ito ◽  
Ken Yoshida ◽  
Gianfranco Balboni ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fluid ◽  
Synovial Tissue ◽  
Synovial Fibroblasts ◽  
Prokineticin 2 ◽  
Physiological Processes ◽  
Sickness Behaviors ◽  
Synovial Tissues ◽  
Fibroblast Like Synoviocytes

Abstract Prokineticin 2 (PK2) is a secreted protein involved in several pathological and physiological processes, including the regulation of inflammation, sickness behaviors, and the circadian rhythm. Recently, it was reported that PK2 is associated with the pathogenesis of collagen-induced arthritis in mice. However, whether PK2 influences the pathogenesis of rheumatoid arthritis (RA) or osteoarthritis (OA) remains unknown. In this study, we collected synovial tissue, plasma, synovial fluid, and fibroblast-like synoviocytes (FLS) from RA and OA patients to analyze the role of PK2 using immunohistochemistry, ELISAs, and tissue superfusion studies. PK2 and its receptors prokineticin receptor (PKR) 1 and 2 were expressed in RA and OA synovial tissues. PKR1 expression in RA synovial tissue was downregulated compared with OA synovial tissue. The PK2 concentration was higher in RA synovial fluid than in OA synovial fluid but similar between RA and OA plasma. PK2 suppressed the production of IL-6 from TNFα-prestimulated OA-FLS, and this effect was attenuated in TNFα-prestimulated RA-FLS. This phenomenon was accompanied by the upregulation of PKR1 in OA-FLS and the downregulation of PK2 and PKR1 in RA-FLS. This study provides a new model to explain some aspects underlying the chronicity of inflammation in RA.

scholarly journals Differential inflammation-mediated function of prokineticin 2 in the synovial fibroblasts of patients with rheumatoid arthritis compared with osteoarthritis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kentaro Noda ◽  
Bianca Dufner ◽  
Haruyasu Ito ◽  
Ken Yoshida ◽  
Gianfranco Balboni ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fluid ◽  
Synovial Tissue ◽  
Synovial Fibroblasts ◽  
Collagen Induced Arthritis ◽  
Prokineticin 2 ◽  
Physiological Processes ◽  
Sickness Behaviors ◽  
Synovial Tissues

AbstractProkineticin 2 (PK2) is a secreted protein involved in several pathological and physiological processes, including the regulation of inflammation, sickness behaviors, and circadian rhythms. Recently, it was reported that PK2 is associated with the pathogenesis of collagen-induced arthritis in mice. However, the role of PK2 in the pathogenesis of rheumatoid arthritis (RA) or osteoarthritis (OA) remains unknown. In this study, we collected synovial tissue, plasma, synovial fluid, and synovial fibroblasts (SF) from RA and OA patients to analyze the function of PK2 using immunohistochemistry, enzyme-linked immunosorbent assays, and tissue superfusion studies. PK2 and its receptors prokineticin receptor (PKR) 1 and 2 were expressed in RA and OA synovial tissues. PKR1 expression was downregulated in RA synovial tissue compared with OA synovial tissue. The PK2 concentration was higher in RA synovial fluid than in OA synovial fluid but similar between RA and OA plasma. PK2 suppressed the production of IL-6 from TNFα-prestimulated OA-SF, and this effect was attenuated in TNFα-prestimulated RA-SF. This phenomenon was accompanied by the upregulation of PKR1 in OA-SF. This study provides a new model to explain some aspects underlying the chronicity of inflammation in RA.

scholarly journals Prostacyclin-IP signaling and prostaglandin E2-EP2/EP4 signaling both mediate joint inflammation in mouse collagen-induced arthritis

2006 ◽  
Vol 203 (2) ◽  
pp. 325-335 ◽  
Author(s):  
Tetsuya Honda ◽  
Eri Segi-Nishida ◽  
Yoshiki Miyachi ◽  
Shuh Narumiya
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fluid ◽  
Joint Inflammation ◽  
Synovial Fibroblasts ◽  
The Other ◽  
Receptor Subtype ◽  
Significant Suppression ◽  
Wild Type ◽  
Collagen Induced Arthritis

Prostaglandin (PG)I2 (prostacyclin [PGI]) and PGE2 are abundantly present in the synovial fluid of rheumatoid arthritis (RA) patients. Although the role of PGE2 in RA has been well studied, how much PGI2 contributes to RA is little known. To examine this issue, we backcrossed mice lacking the PGI receptor (IP) to the DBA/1J strain and subjected them to collagen-induced arthritis (CIA). IP-deficient (IP−/−) mice exhibited significant reduction in arthritic scores compared with wild-type (WT) mice, despite anti-collagen antibody production and complement activation similar to WT mice. IP−/− mice also showed significant reduction in contents of proinflammatory cytokines, such as interleukin (IL)-6 in arthritic paws. Consistently, the addition of an IP agonist to cultured synovial fibroblasts significantly enhanced IL-6 production and induced expression of other arthritis-related genes. On the other hand, loss or inhibition of each PGE receptor subtype alone did not affect elicitation of inflammation in CIA. However, a partial but significant suppression of CIA was achieved by the combined inhibition of EP2 and EP4. Our results show significant roles of both PGI2-IP and PGE2-EP2/EP4 signaling in the development of CIA, and suggest that inhibition of PGE2 synthesis alone may not be sufficient for suppression of RA symptoms.

scholarly journals The Autophagy Level Is Increased in the Synovial Tissues of Patients with Active Rheumatoid Arthritis and Is Correlated with Disease Severity

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Li Zhu ◽  
Huaizhou Wang ◽  
Yu Wu ◽  
Zhengwen He ◽  
Yanghua Qin ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Tissue ◽  
Active Rheumatoid Arthritis ◽  
Synovial Fibroblasts ◽  
Serum Levels ◽  
Serum Markers ◽  
Effector Cells ◽  
Joint Replacement Surgery ◽  
Replacement Surgery ◽  
Synovial Tissues

Rheumatoid arthritis (RA) is a complex and not fully understood autoimmune disease associated with multijoint damage. The main effector cells, the synovial fibroblasts, are apoptosis resistant and hyperplastic which indicate that autophagy level is high in synovial tissue. Real-time PCR, immunocytochemistry, and western blotting were used in this paper to study the autophagy status of the synovial tissues obtained from RA and OA patients at the time of joint replacement surgery. We further evaluated the correlation between autophagy levels with RA activity-associated serum markers with SPSS. The results showed that the expression levels (both in mRNA and in protein level) of autophagy-related proteins (belcin1, Atg5, and LC3) in the synovial tissue of patients with active rheumatoid arthritis (n=20) were significantly higher than those in OA patients (n=16). We further showed that the LC3-II/β-actin relative gray value was strongly correlated with the serum levels of several RA activity-related markers: CRP, ESR, CCP, and RF. Our results indicate that evaluating the autophagy level of synovial biopsies might be a useful way to diagnose RA and to estimate the disease activity. Reducing the expression level of autophagy-related genes might become a new therapeutic target for active rheumatoid arthritis.

CXCL10 and TRAIL Are Upregulated by TXNDC5 in Rheumatoid Arthritis Fibroblast-like Synoviocytes

2017 ◽  
Vol 45 (3) ◽  
pp. 335-340 ◽  
Author(s):  
Bing Xu ◽  
Jian Li ◽  
Changsun Wu ◽  
Chunyan Liu ◽  
Xinfeng Yan ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Synovial Fibroblasts ◽  
And Migration ◽  
Interfering Rna ◽  
Synovial Membranes ◽  
Necrosis Factor ◽  
Fibroblast Like Synoviocytes

Objective.Thioredoxin domain containing 5 (TXNDC5) is highly expressed in synovial membranes of rheumatoid arthritis (RA). Our study aimed to investigate the pathogenic role of TXNDC5 in RA.Methods.PCR arrays, CCK-8 assays, flow cytometry, and transwell migration assays were used to analyze cultured rheumatoid arthritis synovial fibroblasts (RASF).Results.Increased CXCL10 and tumor necrosis factor-related apoptosis-inducing ligand levels were detected in RASF transfected with anti-TXNDC5 small interfering RNA (siRNA), and decreased expression was detected in RASF transfected with TXNDC5-expressing plasmids. Significantly attenuated RASF proliferation and migration, and increased RASF apoptosis, were observed in the siRNA-transfected RASF.Conclusion.Downregulation of TXNDC5 could contribute to RASF antiangiogenic and proapoptotic features through the suppression of CXCL10 and TRAIL (tumor necrosis factor-related apoptosis-inducing ligand).

Urocortin in the synovial tissue of patients with rheumatoid arthritis

2001 ◽  
Vol 100 (6) ◽  
pp. 577-589 ◽  
Author(s):  
Miwa UZUKI ◽  
Hironobu SASANO ◽  
Yasunari MURAMATSU ◽  
Kazuhito TOTSUNE ◽  
Kazuhiro TAKAHASHI ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fluid ◽  
Synovial Tissue ◽  
High Power ◽  
Rt Pcr ◽  
Active Stage ◽  
High Power Field ◽  
Mrna In Situ Hybridization ◽  
Synovial Tissues

Urocortin is a newly identified member of the corticotropin-releasing factor (CRF) neuropeptide family, and is known to be involved in the modulation of the inflammatory process. We examined the expression of urocortin, CRF and their receptors (CRF receptor; CRF-R) in the synovial tissue of patients with rheumatoid arthritis (RA) in order to study the possible biological roles of urocortin. Synovial tissues/fluids were obtained from 38 patients with RA, nine patients with osteoarthritis and four with trauma. We studied the concentration of urocortin in the synovial fluid using RIA, and the expression of urocortin in synovial tissue using immunohistochemistry, mRNA in situ hybridization and reverse transcriptase–PCR (RT-PCR). In addition, we examined the immunolocalization of CRF and the expression of CRF-R1, -R2-α and -R2-β mRNAs utilizing RT-PCR in these synovial tissues. Urocortin concentrations in synovial fluid were higher in RA patients (79.8±154 pg/ml) than in control patients (12.3±4.8 pg/ml; P ≤ 0.05). Urocortin immunoreactivity and mRNA signals were both detected in synovial cells, lymphocytes, fibroblasts and macrophages. The number of urocortin-positive cells in the synovium was significantly higher in RA (73.1±32.1 cells per high-power field) than in control (18.4±10.4 cells per high-power field) patients. In addition, both urocortin immunoreactivity and mRNA signals in the synovium reached maximum levels in the active stage of RA inflammation. Moreover, the number of immunoreactive urocortin-positive cells was significantly correlated with the urocortin concentration in synovial fluid (r = 0.705; P < 0.001) and with histologically defined local inflammatory activity (r = 0.641; P < 0.001). The distribution and number of immunoreactive CRF-positive cells in synovial tissue were similar to those of urocortin-positive cells (r = 0.701; P < 0.001). Urocortin, CRF-R1 and CRF-R2-α mRNAs detected by RT-PCR were expressed in in the synovium of 10/10, 10/10 and 2/10 RA patients respectively, but CRF-R2-β was not expressed. Urocortin was actively synthesized in the synovium of RA patients. The present study suggests that urocortin may play an important role as an autocrine and/or paracrine regulator of synovial inflammation in RA.

scholarly journals Proteomic analysis of synovial tissue in rheumatoid arthritis, OLFM4 promotes fibroblast like synoviocytes proliferation in RA

2020 ◽  
Author(s):  
Xiaoyu Ren ◽  
Ke Xu ◽  
Jing Xu ◽  
Manman Geng ◽  
Chao Lu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Tissue ◽  
Western Blotting ◽  
Protein Processing ◽  
Protein Profiles ◽  
Kegg Analysis ◽  
Unique Protein ◽  
On Line ◽  
Synovial Tissues ◽  
Fibroblast Like Synoviocytes

Abstract Background To understand the roles of synovial tissue in rheumatoid arthritis (RA), we comprehensively investigated the protein profiles of synovial tissues in patients with RA and osteoarthritis (OA). Methods Protein were isolated from synovial tissues of 46 patients (22 with RA, 24with OA). Proteins were digested and labeled with TMT kit. All the peptide were send to LC-MS/MS analysis, and processed with Mascot and Proteome Discovery (version 1.4) search engines. All the protein data were analysis with Gene ontology (GO) and KEGG on line database. Four up-regulated protein were examined with western blotting and IHC. The RNAi were used for revealing the OLFM4 function in FLS. Results In total, over 500 proteins were identified as the different expression protein compared RA and OA synovia tissues, including 239 proteins were up-regulated in RA, and 271 proteins were up-regulated in OA. GO and KEGG analysis of the different expressed protein mostly identified as developmental processes and protein processing in ER. RT-qPCR, western blotting and IHC confirmed that there was a strong over expressed OLFM4 in RA synovia tissues. OLFM4 could be up-regulated under inflammatory stimulation, and participate in fibroblast like synoviocytes proliferation. Conclusion patients with RA possessed considerably different protein profiles of synovial tissues from with OA. The unique protein profiles of RA synovial tissues, such as the OLFM4 and MZB1 had been up-regulated compared to the OA, may reflect the pathophysiology of RA.

scholarly journals MiRNA-126 expression inhibits IL-23R mediated TNF-α or IFN-γ production in fibroblast-like synoviocytes in a mice model of collagen-induced rheumatoid arthritis

APOPTOSIS ◽  
2018 ◽  
Vol 23 (11-12) ◽  
pp. 607-615 ◽  
Author(s):  
Jie Gao ◽  
Ruina Kong ◽  
Xiaoli Zhou ◽  
Lianmei Ji ◽  
Ju Zhang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fluid ◽  
Synovial Tissue ◽  
Mice Model ◽  
Collagen Induced Arthritis ◽  
Tnf Α ◽  
Ifn Γ ◽  
Negative Controls ◽  
Fibroblast Like Synoviocytes

Abstract Both miR-126 and IL-23R affect rheumatoid arthritis (RA) procession. This study aimed to investigate the association of miR-126 and IL-23R and the possible modulation of miR-126 to RA pathogenesis. Serum, synovial tissue and synovial fluid were collected from patients with RA, and expression of miR-126, IL-23R, TNF-α and IFN-γ were detected. Fibroblast-like synoviocytes (FLS) was established using a collagen-induced arthritis mice model. The expression of miR-126 was manual intervened using pro-miR-126 and anti-miR-126 encoding lentivirus plasmids, or miR-126 agonists and corresponding negative controls. MiR-126 expression was inhibited in RA patients when compared with controls (P < 0.05). TNF-α and IFN-γ production and IL-23R expression were significantly upregulated in RA patients when compared to controls (P < 0.05). In pro-miR-126 treated FLS cells, the administration of pro-miR-126 plasmids upregulated miR-126, but inhibited IL-23R, TNF-α and IFN-γ expression or production. Moreover, the miR-126 agonist reversed the effects of the anti-miR-126 plasmid on FLS. These results revealed that miR-126 negative regulated the expression of IL-23R, TNF-α and IFN-γ. These results suggest the key impact of miR-126 on RA procession. Moreover, pro-miR-126 might be explored to be a potential therapy for RA.

scholarly journals Relative Expression of Soluble tnf Versus Transmembrane tnf in Spondyloarthritis

2017 ◽  
Vol 4 (1) ◽  
pp. 56
Author(s):  
Huriatul Masdar
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fluid ◽  
Synovial Tissue ◽  
Differential Regulation ◽  
Mrna Levels ◽  
Tnf Receptors ◽  
Relative Expression ◽  
Synovial Tissues

TNF is important in rheumatoid arthritis (RA) and spondyloarthritis (SpA) pathogenesis. Recently reports showedsTNF levels were significantly lower in SpA than RA synovial fluid (SF). Therefore, the differential regulation of TNFin both diseases were investigated focusing on the balance of sTNF-tmTNF and both TNF receptors expression. Synovialfluid from 22 RA and 25 SpA were analyzed by ELISA. sTNF was confirmed significantly higher in RA than SpA.Total TNF of synovial tissues assessed by qPCR showed similar levels, suggesting a higher tmTNF/sTNF ratio in SpA.The levels of sTNF-R1 and sTNF-R2 were significantly lower in SpA than RA SF. Interestingly, sTNF-R2/sTNF-R1increased in SpA. qPCR on synovial tissue showed similar mRNA levels for TNF-R2 but decrease of TNF-R1 in SpA.IL-6R levels did not showed differences and TIMP-3 tended to be higher in RA than in SpA SF. In conclusion, weobserved a shift from sTNF/TNF-R1 in RA to tmTNF/TNF-R2 in SpA.

scholarly journals Uridine Diphosphate (UDP) Promotes Rheumatoid Arthritis Through P2Y6 Activation

2020 ◽  
Author(s):  
Hongxing Wang ◽  
Hui Wu ◽  
Kehua Fang ◽  
Xiaotian Chang
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Proliferation ◽  
Synovial Fluid ◽  
Real Time ◽  
Uridine Diphosphate ◽  
Collagen Induced Arthritis ◽  
Synovial Tissues ◽  
And Migration ◽  
G Protein Coupled ◽  
Fibroblast Like Synoviocytes

Abstract Background: Uridine diphosphate (UDP) is an extracellular nucleotide signaling molecule implicated in diverse biological processes via specific activation of the metabotropic pyrimidine and purine nucleotide receptor pyrimidinergic receptor P2Y, G Protein-Coupled, 6 (P2Y6).Methods: This study used a quasi-targeted liquid chromatography-mass spectrometry (LC-MS) approach to investigate the unique expression of metabolites in rheumatoid arthritis (RA) synovial fluid (SF) (n=10) with samples from osteoarthritis (OA) as controls (n=10). RA fibroblast-like synoviocytes (FLSs) were collected from synovial tissues and cultured with UDP or MRS2578, P2Y6 antagonist, and FLSs from OA was used as controls. Rats with collagen-induced arthritis (CIA) were established and injected with UDP or MRS2578 or both. P2Y6 expression was examined using real-time PCR, Western blotting and Immunohistochemistry. Cell proliferation, apoptosis and migration of FLSs were measured using CCK-8 assay, real-time cell analysis, flow cytometry, the wound healing assay and transwell assay. The concentration of UDP in culture medium, synovial fluid and peripheral blood RA and CIA rats was measured using a Transcreener UDP Assay, IL-6 was measured using ELISA and flow assay, and other pro-inflammatory cytokines was measured using Th1/Th2 Subgroup Detection Kit. Results: LC-MS analysis showed that the UDP level is not only higher in RA SF than in OA SF but also positively correlated with anticyclic citrullinated peptide (anti-CCP) and rheumatoid factor (RF) levels in RA. The increased UDP concentration was verified in the plasma and SF samples of RA patients (n=36) and healthy volunteers (n=36), and the levels were significantly correlated with RF and anti-CCP level in the samples. The study also found that UDP stimulated the cell proliferation, migration and interleukin-6 (IL-6) secretion of RA FLSs and inhibited their apoptosis in the culture. The P2Y6 antagonist MRS2578 inhibited this effect of UDP in the culture. UDP injection accelerated the development of collagen-induced arthritis (CIA) in a rat model and stimulated IL-6 production, but simultaneous injection of MRS2578 suppressed these effects and alleviated CIA. P2Y6 expression was increased in RA and CIA synovial tissues and was unaltered by UDP treatment. UDP treatment and P2Y6 activity didn’t change levels of other proinflammatory cytokines in cultured FLSs and CIA rats.Conclusion: These results suggest that UDP is highly expressed in RA and stimulates RA pathogenesis by promoting P2Y6 activities to increase IL-6 production.

scholarly journals AB0100 PHENOTYPIC AND FUNCTIONAL CHARACTERIZATION OF SYNOVIAL FLUID-DERIVED FIBROBLAST-LIKE SYNOVIOCYTES IN RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1349.1-1349
Author(s):  
D. Køster ◽  
J. H. Egedal ◽  
M. Hvid ◽  
M. R. Jakobsen ◽  
U. Müller-Ladner ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fluid ◽  
Synovial Tissue ◽  
Mononuclear Cells ◽  
Functional Characterization ◽  
Human Cartilage ◽  
Fibroblast Like Synoviocytes

Background:Fibroblast-like synoviocytes (FLS) are central cellular components in persistent inflammatory joint diseases such as rheumatoid arthritis (RA). Pathological subsets of FLS have been identified from synovial tissue. However, the synovial tissue obtained from arthroplasty procedures is acquired at late disease stages and the cellular yield obtained from synovial tissue biopsies is fairly low. Collectively, challenging the robustness of human RAin vivoandin vitromodels. FLS obtained from the synovial fluid (SF-FLS) are proposed as an alternative source of FLS, but a detailed phenotypical and functional characterization of FLS subsets from the synovial fluid has not been performed.Objectives:The aim of this study was to determine the phenotypical and functional characteristics of synovial fluid-derived fibroblast-like synoviocytes in rheumatoid arthritis.Methods:In the present study, paired peripheral blood mononuclear cells (PBMC) and SF-FLS from patients with RA were obtained (n=7). FLS were isolated from the synovial fluid by a strict trypsinization protocol1and their cellular characteristics and functionality were evaluated at passage 4. Monocultures (SF-FLS) and autologous co-cultures (SF-FLS and PBMC) were established from five patients with RA and subsequently evaluated by flow cytometry, Western blotting and multiplex immunoassays. Human cartilage-sponges (n=3) with SF-FLS and without SF-FLS (n=3) were co-implanted subcutaneously in SCID mice (n=15), mice with only cell-free human cartilage-sponges were used as controls (n=12). After 45 days, the implants were evaluated using stained sections to determine the SF-FLS invasion score based on perichondrocytic cartilage degradation. Data are expressed as median (25-75 percentile). P-values <0.05 were considered statistically significant.Results:The homogeneous subpopulations of FLS, isolated from the synovial fluid, were negative for CD34 and CD45 [98.9%, (97.5-99.7]) and positive for Thy-1 and PDPN [94.6%, (79.9-97.4]). Without stimulation, RA SF-FLS showed high and comparable levels of NFκB related pathway proteins and secreted multiple pro-inflammatory cytokines and chemokines dominated by IL-6 [2648 pg/mL, (1327-6116)] and MCP-1 [2458 pg/mL, (692-8719)]. SF-FLS increased their ICAM-1 and HLA-DR expression after encountering autologous PBMCs (p<0.01), (p<0.05). Further, SF-FLS and PBMC interacted synergistically in a co-culture model of RA and significantly increasing the secretion of several cytokines (IL-1β, IL-2, IL-6, (p<0.01)) and a chemokine (MCP-1, (p<0.01)). The invasion score of the human SF-FLSin vivowas at primary site, [1.6, (1.3-1.7)] and contralateral implantation site [1.5, (1.1-2.2)]. The invasion score of the human SF-FLS-containing implants both at primary and contralateral site were significantly higher compared with cartilage-sponges evaluated from SF-FLS-free control mice (p<0001).Conclusion:This phenotypical and functional characterization of SF-FLS, acquired and activated at the site of pathology, lays a foundation for establishingin vivoandin vitroFLS models. These FLS models will be beneficial in our understanding of the role of this cellular subset in arthritis and for characterization of drugs specifically targeting this pathological RA FLS subset.References:[1]Nielsen M. A. et al. Responses to Cytokine Inhibitors Associated with Cellular Composition in Models of Immune-Mediated Inflammatory Arthritis. ACR Open Rheumatology, 2(1):3-10.http://doi.org/10.1002/acr2.11094Disclosure of Interests:Ditte Køster: None declared, Johanne Hovgaard Egedal: None declared, Malene Hvid: None declared, Martin Roelsgaard Jakobsen: None declared, Ulf Müller-Ladner Speakers bureau: Biogen, Bent Deleuran: None declared, Tue Wenzel Kragstrup Shareholder of: iBio Tech ApS, Consultant of: Bristol-Myers Squibb, Speakers bureau: TWK has engaged in educational activities talking about immunology in rheumatic diseases receiving speaking fees from Pfizer, Bristol-Myers Squibb, Eli Lilly, Novartis, and UCB., Elena Neumann: None declared, Morten Aagaard Nielsen: None declared

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