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

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

doi:10.1371/journal.pone.0197001

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

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

Institut for Klinisk Medicin

4 Citationer (Scopus)

39 Downloads (Pure)

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.

Originalsprog	Engelsk
Artikelnummer	e0197001
Tidsskrift	PLoS ONE
Vol/bind	13
Udgave nummer	5
Antal sider	17
ISSN	1932-6203
DOI	https://doi.org/10.1371/journal.pone.0197001
Status	Udgivet - maj 2018

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10.1371/journal.pone.0197001Licens: CC BY

journal.pone.0197001Forlagets udgivne version, 1,56 MBLicens: CC BY

Citationsformater

Andersen, M., Boesen, M., Ellegaard, K., Söderström, K., Søe, N. H., Spee, P., Mørch, U. G. W., Torp-Pedersen, S., Bartels, E. M., Danneskiold-Samsøe, B., Karlsson, L., & Bliddal, H. (2018). Association between IL-6 production in synovial explants from rheumatoid arthritis patients and clinical and imaging response to biologic treatment: A pilot study. PLoS ONE, 13(5), Artikel e0197001. https://doi.org/10.1371/journal.pone.0197001

Andersen, M, Boesen, M, Ellegaard, K, Söderström, K, Søe, NH, Spee, P, Mørch, UGW, Torp-Pedersen, S, Bartels, EM, Danneskiold-Samsøe, B, Karlsson, L & Bliddal, H 2018, 'Association between IL-6 production in synovial explants from rheumatoid arthritis patients and clinical and imaging response to biologic treatment: A pilot study', PLoS ONE, bind 13, nr. 5, e0197001. https://doi.org/10.1371/journal.pone.0197001

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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.",

keywords = "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",

author = "Martin Andersen and Mikael Boesen and Karen Ellegaard and Kalle S{\"o}derstr{\"o}m and S{\o}e, {Niels H} and Pieter Spee and M{\o}rch, {Ulrik G W} and S{\o}ren Torp-Pedersen and Bartels, {Else M} and Bente Danneskiold-Sams{\o}e and Lars Karlsson and Henning Bliddal",

year = "2018",

month = may,

doi = "10.1371/journal.pone.0197001",

language = "English",

volume = "13",

journal = "PLoS ONE",

issn = "1932-6203",

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TY - JOUR

T1 - Association between IL-6 production in synovial explants from rheumatoid arthritis patients and clinical and imaging response to biologic treatment

T2 - A pilot study

AU - Andersen, Martin

AU - Boesen, Mikael

AU - Ellegaard, Karen

AU - Söderström, Kalle

AU - Søe, Niels H

AU - Spee, Pieter

AU - Mørch, Ulrik G W

AU - Torp-Pedersen, Søren

AU - Bartels, Else M

AU - Danneskiold-Samsøe, Bente

AU - Karlsson, Lars

AU - Bliddal, Henning

PY - 2018/5

Y1 - 2018/5

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Antirheumatic Agents/therapeutic use

KW - Arthritis, Rheumatoid/diagnostic imaging

KW - Case-Control Studies

KW - Chemokine CCL2/metabolism

KW - Female

KW - Humans

KW - Image Processing, Computer-Assisted/methods

KW - In Vitro Techniques

KW - Interleukin-6/analysis

KW - Male

KW - Middle Aged

KW - Pilot Projects

KW - Prognosis

KW - Synovial Membrane/diagnostic imaging

KW - Tissue Culture Techniques

KW - Ultrasonography, Doppler, Color/methods

U2 - 10.1371/journal.pone.0197001

DO - 10.1371/journal.pone.0197001

M3 - Journal article

C2 - 29787569

SN - 1932-6203

VL - 13

JO - PLoS ONE

JF - PLoS ONE

IS - 5

M1 - e0197001

ER -

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

Abstract

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