FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4283642783> ?p ?o ?g. }

• W4283642783 endingPage "463" @default.
• W4283642783 startingPage "462.1" @default.
• W4283642783 abstract "Background Fibroblast-like synoviocytes (FLS) are pivotal mediators of rheumatoid synovitis expansive growth and invasiveness which respond insufficiently to disease-modifying antirheumatic drugs. Galectin-9 (Gal-9) is a lectin with well-conserved carbohydrate-recognition domains. Gal-9 has been reported to have both pro- and anti-inflammatory properties based on its ability to modulate RA FLS. Gal-9 levels are elevated in serum of rheumatoid arthritis (RA) patients, and high levels of Gal-9 have been identified in both the synovial fluid and in the inflamed synovial tissue of patients with RA. Objectives To investigate the role of Gal-9 as a biomarker for disease severity in treatment naïve patients with early RA and to study aspects of Gal-9 effects on inflammatory RA FLS. Methods Soluble plasma Gal-9 was measured in patients with newly diagnosed, treatment-naïve RA (n = 98) and in Healthy (HC) (n = 48) (Table 1). Over a 2-year period patients were randomized to either MTX alone or MTX and anti-TNF antibody treatments. Serial measurements of disease activity (DAS28CRP) were collected to evaluate the disease course. In another cohort of patients with established RA, plasma and synovial fluid samples were also examined for Gal-9 (n = 18) (Table 1). Synovial fluid mononuclear cells (SFMC) from established RA patients were used to harvest RA FLS (n=7). Osteoarthritis FLS were used as disease controls and obtained from patients with knee OA undergoing joint replacement surgery (n = 5). Monocultures of synovial fluid derived FLS (SF-FLS) (n= 6) and autologous co-cultures of SF-FLS and peripheral blood mononuclear cells (PBMC) were established (n=7) and subsequently analyzed by flow cytometry, MTT assay, and ELISA. In vitro, cultures were treated with a neutralizing anti-Gal-9 antibody. Table 1. Patient characteristics Early RA (n=98) Established RA (n=18) HC (n=48) Time after treatment initiation (months) 0 3 24 84 (12-288) Disease activity DAS28CRP (0-10) 5.7 (5.1-6.4) 2.1 (1.8-3.2) 2.0 (1.8-2.7) 5.0 (3.2-5.5) - Gal-9 levels (pg/ml) Plasma 3315 (2683-4421) 3217 (2706-4250) 2904 (2639-3411) 2190 (1652-2852) Synovial fluid 21246 (13832-34727) Patient characteristics. Data are expressed as median with IQR range unless otherwise indicated. Results Patients with early and established RA had increased plasma levels of Gal-9 compared with HCs (P < 0.05) (Table 1) and levels of Gal-9 correlated positively with swollen joint counts at baseline (rho = 0.344, P < 0.05). The levels remained unaffected by treatment with MTX alone or by a combination of MTX and anti-TNF antibodies. Gal-9 levels were markedly elevated in the synovial fluid of chronic RA patients compared with the corresponding plasma samples (P < 0.05) (Table 1). In vitro, a neutralizing Gal-9 antibody mediated a 40% decrease in MCP-1 secretion (P < 0.05) and a 30% decrease in IL-6 secretion (P < 0.05) in RA FLS monocultures. In OA FLS, addition of anti-Gal-9 antibodies comparably decreased the production of both MCP-1 (P < 0.05) and IL-6 (P < 0.05). The changes in cytokine production were not attributable to reduction in the fraction of inflammatory FLS (CD34 - PDPN + THY1 + ), decreased viability or proliferation. We further investigated if the effect of neutralizing Gal-9 persisted in co-cultures between FLS and autologous PBMC. Also in this setting, neutralization of Gal-9 mediated a 40% reduction in both MCP-1 and IL-6 (P < 0.05, P < 0.05). Conclusion Pretreatment plasma Gal-9 levels in patients with newly diagnosed RA were increased and correlated with baseline clinical disease activity but remained elevated during goal directed synovitis suppressive therapy. In addition, in vitro neutralization of Gal-9 decreased MCP-1 and IL-6 production in a subset of FLS linked to RA pathology. Collectively these findings indicate that Gal-9 overexpression is a co-player in the causation of acute and persistent RA synovitis by enhancing pro-inflammatory FLS pathways. Acknowledgements We thank Karin Skovgård Sørensen (Dept. of Biomedicine, Aarhus University) for technical assistance concerning the ELISA data and the FACS Core Facility (Aarhus University, Denmark) for technical assistant regarding Flow cytometry. We thank medical doctors and nurses at the Department of Rheumatology, Aarhus University Hospital for helping to collect the patient samples. We kindly acknowledge the generous grants from Aarhus University Research Foundation and the Danish Rheumatism Association. Disclosure of Interests None declared." @default.
• W4283642783 created "2022-06-29" @default.
• W4283642783 creator A5009975931 @default.
• W4283642783 creator A5012763337 @default.
• W4283642783 creator A5029636602 @default.
• W4283642783 creator A5029765691 @default.
• W4283642783 creator A5042428908 @default.
• W4283642783 creator A5056189838 @default.
• W4283642783 creator A5063586848 @default.
• W4283642783 creator A5071248640 @default.
• W4283642783 creator A5081575398 @default.
• W4283642783 creator A5088476180 @default.
• W4283642783 creator A5089651956 @default.
• W4283642783 date "2022-05-23" @default.
• W4283642783 modified "2023-10-17" @default.
• W4283642783 title "POS0415 PLASMA GALECTIN-9 IS ASSOCIATED WITH CLINICAL DISEASE ACTIVITY IN TREATMENT NAÏVE EARLY RHEUMATOID ARTHRITIS, UNAFFECTED BY DMARD TREATMENT, AND IN VITRO MODULATES THE SECRETION OF MCP-1 AND IL-6 IN RHEUMATOID ARTHRITIS SYNOVIAL FIBROBLASTS" @default.
• W4283642783 doi "https://doi.org/10.1136/annrheumdis-2022-eular.1213" @default.
• W4283642783 hasPublicationYear "2022" @default.
• W4283642783 type Work @default.
• W4283642783 citedByCount "0" @default.
• W4283642783 crossrefType "journal-article" @default.
• W4283642783 hasAuthorship W4283642783A5009975931 @default.
• W4283642783 hasAuthorship W4283642783A5012763337 @default.
• W4283642783 hasAuthorship W4283642783A5029636602 @default.
• W4283642783 hasAuthorship W4283642783A5029765691 @default.
• W4283642783 hasAuthorship W4283642783A5042428908 @default.
• W4283642783 hasAuthorship W4283642783A5056189838 @default.
• W4283642783 hasAuthorship W4283642783A5063586848 @default.
• W4283642783 hasAuthorship W4283642783A5071248640 @default.
• W4283642783 hasAuthorship W4283642783A5081575398 @default.
• W4283642783 hasAuthorship W4283642783A5088476180 @default.
• W4283642783 hasAuthorship W4283642783A5089651956 @default.
• W4283642783 hasBestOaLocation W42836427831 @default.
• W4283642783 hasConcept C126322002 @default.
• W4283642783 hasConcept C142724271 @default.
• W4283642783 hasConcept C185592680 @default.
• W4283642783 hasConcept C203014093 @default.
• W4283642783 hasConcept C204787440 @default.
• W4283642783 hasConcept C2776164576 @default.
• W4283642783 hasConcept C2776268809 @default.
• W4283642783 hasConcept C2777077863 @default.
• W4283642783 hasConcept C2777575956 @default.
• W4283642783 hasConcept C2779244835 @default.
• W4283642783 hasConcept C2781197716 @default.
• W4283642783 hasConcept C55493867 @default.
• W4283642783 hasConcept C71924100 @default.
• W4283642783 hasConcept C90924648 @default.
• W4283642783 hasConceptScore W4283642783C126322002 @default.
• W4283642783 hasConceptScore W4283642783C142724271 @default.
• W4283642783 hasConceptScore W4283642783C185592680 @default.
• W4283642783 hasConceptScore W4283642783C203014093 @default.
• W4283642783 hasConceptScore W4283642783C204787440 @default.
• W4283642783 hasConceptScore W4283642783C2776164576 @default.
• W4283642783 hasConceptScore W4283642783C2776268809 @default.
• W4283642783 hasConceptScore W4283642783C2777077863 @default.
• W4283642783 hasConceptScore W4283642783C2777575956 @default.
• W4283642783 hasConceptScore W4283642783C2779244835 @default.
• W4283642783 hasConceptScore W4283642783C2781197716 @default.
• W4283642783 hasConceptScore W4283642783C55493867 @default.
• W4283642783 hasConceptScore W4283642783C71924100 @default.
• W4283642783 hasConceptScore W4283642783C90924648 @default.
• W4283642783 hasIssue "Suppl 1" @default.
• W4283642783 hasLocation W42836427831 @default.
• W4283642783 hasOpenAccess W4283642783 @default.
• W4283642783 hasPrimaryLocation W42836427831 @default.
• W4283642783 hasRelatedWork W2104646232 @default.
• W4283642783 hasRelatedWork W2111012346 @default.
• W4283642783 hasRelatedWork W2171060354 @default.
• W4283642783 hasRelatedWork W2394737345 @default.
• W4283642783 hasRelatedWork W2409257764 @default.
• W4283642783 hasRelatedWork W2413413704 @default.
• W4283642783 hasRelatedWork W2416590574 @default.
• W4283642783 hasRelatedWork W2554753859 @default.
• W4283642783 hasRelatedWork W4214673592 @default.
• W4283642783 hasRelatedWork W4310677094 @default.
• W4283642783 hasVolume "81" @default.
• W4283642783 isParatext "false" @default.
• W4283642783 isRetracted "false" @default.
• W4283642783 workType "article" @default.