Association between IL-6 production in synovial explants from rheumatoid arthritis patients and clinical and imaging response to biologic treatment: A pilot study

Research output: Contribution to journalJournal articleResearchpeer-review


  • Martin Andersen
  • Boesen, Mikael Ploug
  • Karen Ellegaard
  • Kalle Söderström
  • Niels H Søe
  • Pieter Spee
  • Ulrik G W Mørch
  • Søren Torp-Pedersen
  • Else M Bartels
  • Bente Danneskiold-Samsøe
  • Lars Karlsson
  • Bliddal, Henning

INTRODUCTION: The need for biomarkers which can predict disease course and treatment response in rheumatoid arthritis (RA) is evident. We explored whether clinical and imaging responses to biologic disease modifying anti-rheumatic drug treatment (bDMARD) were associated with the individual's mediator production in explants obtained at baseline.

METHODS: RA Patients were evaluated by disease activity score 28 joint C-reactive protein (DAS 28-)), colour Doppler ultrasound (CDUS) and 3 Tesla RA magnetic resonance imaging scores (RAMRIS). Explants were established from synovectomies from a needle arthroscopic procedure prior to initiation of bDMARD. Explants were incubated with the bDMARD in question, and the productions of interleukin-6 (IL-6), monocyte chemo-attractive protein-1 (MCP-1) and macrophage inflammatory protein-1-beta (MIP-1b) were measured by multiplex immunoassays. The changes in clinical and imaging variables following a minimum of 3 months bDMARD treatment were compared to the baseline explant results. Mixed models and Spearman's rank correlations were performed. P-values below 0.05 were considered statistically significant.

RESULTS: 16 patients were included. IL-6 production in bDMARD-treated explants was significantly higher among clinical non-responders compared to responders (P = 0.04), and a lack of suppression of IL-6 by the bDMARDS correlated to a high DAS-28 (ρ = 0.57, P = 0.03), CDUS (ρ = 0.53, P = 0.04) and bone marrow oedema (ρ = 0.56, P = 0.03) at follow-up. No clinical association was found with explant MCP-1 production. MIP-1b could not be assessed due to a large number of samples below the detection limit.

CONCLUSIONS: Synovial explants appear to deliver a disease-relevant output testing which when carried out in advance of bDMARD treatment can potentially pave the road for a more patient tailored treatment approach with better treatment effects.

Original languageEnglish
Article numbere0197001
JournalPLoS ONE
Issue number5
Number of pages17
Publication statusPublished - 2018

    Research areas

  • Adult, Aged, Antirheumatic Agents/therapeutic use, Arthritis, Rheumatoid/diagnostic imaging, Case-Control Studies, Chemokine CCL2/metabolism, Female, Humans, Image Processing, Computer-Assisted/methods, In Vitro Techniques, Interleukin-6/analysis, Male, Middle Aged, Pilot Projects, Prognosis, Synovial Membrane/diagnostic imaging, Tissue Culture Techniques, Ultrasonography, Doppler, Color/methods

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