1. Association between IL-6 production in synovial explants from rheumatoid arthritis patients and clinical and imaging response to biologic treatment: A pilot study
- Author
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M. Andersen, Niels Henrik Søe, Ulrik Morch, Bente Danneskiold-Samsøe, Søren Torp-Pedersen, Mikael Boesen, Else Marie Bartels, Kalle Söderström, Pieter Spee, Karen Ellegaard, Henning Bliddal, and Lars Karlsson
- Subjects
Male ,0301 basic medicine ,Image Processing ,lcsh:Medicine ,Antirheumatic Agents/therapeutic use ,Pilot Projects ,Gastroenterology ,Arthroscopic procedure ,Diagnostic Radiology ,Arthritis, Rheumatoid ,Tissue Culture Techniques ,Explant Cultures ,0302 clinical medicine ,Ultrasound Imaging ,Image Processing, Computer-Assisted ,Medicine and Health Sciences ,Medicine ,Ultrasonography, Doppler, Color ,lcsh:Science ,Musculoskeletal System ,Chemokine CCL2 ,Multidisciplinary ,biology ,medicine.diagnostic_test ,Pharmaceutics ,Radiology and Imaging ,Synovial Membrane ,Middle Aged ,Wrist ,Prognosis ,Magnetic Resonance Imaging ,Interleukin-6/analysis ,Arms ,Antirheumatic Agents ,Rheumatoid arthritis ,Synovial Membrane/diagnostic imaging ,Engineering and Technology ,Female ,Biological Cultures ,Anatomy ,Research Article ,Adult ,Treatment response ,medicine.medical_specialty ,Image Processing, Computer-Assisted/methods ,Imaging Techniques ,Immunology ,Rheumatoid Arthritis ,In Vitro Techniques ,Biologic treatment ,Research and Analysis Methods ,Autoimmune Diseases ,03 medical and health sciences ,Pharmacotherapy ,Rheumatology ,Drug Therapy ,Diagnostic Medicine ,Internal medicine ,Humans ,Interleukin 6 ,Aged ,030203 arthritis & rheumatology ,Interleukin-6 ,business.industry ,Arthritis ,Limbs (Anatomy) ,lcsh:R ,Biology and Life Sciences ,Ultrasonography, Doppler, Color/methods ,Magnetic resonance imaging ,medicine.disease ,Joints (Anatomy) ,030104 developmental biology ,Chemokine CCL2/metabolism ,Case-Control Studies ,Signal Processing ,biology.protein ,Clinical Immunology ,lcsh:Q ,Clinical Medicine ,business ,Arthritis, Rheumatoid/diagnostic imaging ,Explant culture - Abstract
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.
- Published
- 2018
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