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CXCL13 predicts disease activity in early rheumatoid arthritis and could be an indicator of the therapeutic ‘window of opportunity’
INTRODUCTION: A key phenomenon in rheumatoid arthritis is the formation of lymphoid follicles in the inflamed synovial membrane. C-X-C motif chemokine 13 (CXCL13) is central in this process as it attracts C-X-C chemokine receptor type 5 (CXCR5)-expressing B cells and T follicular helper cells to the...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4201737/ https://www.ncbi.nlm.nih.gov/pubmed/25249397 http://dx.doi.org/10.1186/s13075-014-0434-z |
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author | Greisen, Stinne Ravn Schelde, Karen Kræmmer Rasmussen, Tue Kruse Kragstrup, Tue Wenzel Stengaard-Pedersen, Kristian Hetland, Merete Lund Hørslev-Petersen, Kim Junker, Peter Østergaard, Mikkel Deleuran, Bent Hvid, Malene |
author_facet | Greisen, Stinne Ravn Schelde, Karen Kræmmer Rasmussen, Tue Kruse Kragstrup, Tue Wenzel Stengaard-Pedersen, Kristian Hetland, Merete Lund Hørslev-Petersen, Kim Junker, Peter Østergaard, Mikkel Deleuran, Bent Hvid, Malene |
author_sort | Greisen, Stinne Ravn |
collection | PubMed |
description | INTRODUCTION: A key phenomenon in rheumatoid arthritis is the formation of lymphoid follicles in the inflamed synovial membrane. C-X-C motif chemokine 13 (CXCL13) is central in this process as it attracts C-X-C chemokine receptor type 5 (CXCR5)-expressing B cells and T follicular helper cells to the follicle. We here examine the role of CXCL13 and its association with disease in patients with treatment-naïve early rheumatoid arthritis. METHODS: Plasma samples from patients in the OPERA trial were examined for CXCL13 at treatment initiation and after 6 months of treatment with either methotrexate plus placebo (DMARD) (n = 37) or methotrexate plus adalimumab (DMARD + ADA) (n = 39). Treatment outcome was evaluated after 1 and 2 years. CXCL13 plasma levels in healthy volunteers (n = 38) were also examined. RESULTS: Baseline CXCL13 plasma levels were increased in early rheumatoid arthritis patients in comparison with healthy volunteers. Also, plasma CXCL13 correlated positively with disease activity parameters; swollen joint count 28 (rho = 0.34) and 40 (rho = 0.39), visual analog score (rho = 0.38) and simplified disease activity index (rho = 0.25) (all P <0.05). CXCL13 levels decreased a significantly twofold more in the DMARD + ADA group than in the DMARD group. Baseline CXCL13 plasma levels in the DMARD group correlated inversely with disease activity parameters; disease activity score in 28 joints, four variables, C-reactive protein based (DAS28CRP) (rho = 0.58, P <0.05) at 12 months. High baseline CXCL13 was associated with remission (DAS28CRP less than 2.6) after 2 years. CONCLUSIONS: In treatment-naïve early rheumatoid arthritis patients, plasma CXCL13 levels were associated with joint inflammation. Furthermore, patients with high baseline plasma CXCL13 levels had an improved chance of remission after 2 years. We propose that high CXCL13 concentrations indicate recent onset of inflammation that may respond better to early aggressive treatment. Thus, high levels of CXCL13 could reflect the ‘the window of opportunity’ for optimal treatment effect. TRIAL REGISTRATION: Clinicaltrial.gov NCT00660647. Registered 10 April 2008 |
format | Online Article Text |
id | pubmed-4201737 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-42017372014-10-19 CXCL13 predicts disease activity in early rheumatoid arthritis and could be an indicator of the therapeutic ‘window of opportunity’ Greisen, Stinne Ravn Schelde, Karen Kræmmer Rasmussen, Tue Kruse Kragstrup, Tue Wenzel Stengaard-Pedersen, Kristian Hetland, Merete Lund Hørslev-Petersen, Kim Junker, Peter Østergaard, Mikkel Deleuran, Bent Hvid, Malene Arthritis Res Ther Research Article INTRODUCTION: A key phenomenon in rheumatoid arthritis is the formation of lymphoid follicles in the inflamed synovial membrane. C-X-C motif chemokine 13 (CXCL13) is central in this process as it attracts C-X-C chemokine receptor type 5 (CXCR5)-expressing B cells and T follicular helper cells to the follicle. We here examine the role of CXCL13 and its association with disease in patients with treatment-naïve early rheumatoid arthritis. METHODS: Plasma samples from patients in the OPERA trial were examined for CXCL13 at treatment initiation and after 6 months of treatment with either methotrexate plus placebo (DMARD) (n = 37) or methotrexate plus adalimumab (DMARD + ADA) (n = 39). Treatment outcome was evaluated after 1 and 2 years. CXCL13 plasma levels in healthy volunteers (n = 38) were also examined. RESULTS: Baseline CXCL13 plasma levels were increased in early rheumatoid arthritis patients in comparison with healthy volunteers. Also, plasma CXCL13 correlated positively with disease activity parameters; swollen joint count 28 (rho = 0.34) and 40 (rho = 0.39), visual analog score (rho = 0.38) and simplified disease activity index (rho = 0.25) (all P <0.05). CXCL13 levels decreased a significantly twofold more in the DMARD + ADA group than in the DMARD group. Baseline CXCL13 plasma levels in the DMARD group correlated inversely with disease activity parameters; disease activity score in 28 joints, four variables, C-reactive protein based (DAS28CRP) (rho = 0.58, P <0.05) at 12 months. High baseline CXCL13 was associated with remission (DAS28CRP less than 2.6) after 2 years. CONCLUSIONS: In treatment-naïve early rheumatoid arthritis patients, plasma CXCL13 levels were associated with joint inflammation. Furthermore, patients with high baseline plasma CXCL13 levels had an improved chance of remission after 2 years. We propose that high CXCL13 concentrations indicate recent onset of inflammation that may respond better to early aggressive treatment. Thus, high levels of CXCL13 could reflect the ‘the window of opportunity’ for optimal treatment effect. TRIAL REGISTRATION: Clinicaltrial.gov NCT00660647. Registered 10 April 2008 BioMed Central 2014-09-24 2014 /pmc/articles/PMC4201737/ /pubmed/25249397 http://dx.doi.org/10.1186/s13075-014-0434-z Text en © Greisen et al.; licensee BioMed Central Ltd. 2014 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Greisen, Stinne Ravn Schelde, Karen Kræmmer Rasmussen, Tue Kruse Kragstrup, Tue Wenzel Stengaard-Pedersen, Kristian Hetland, Merete Lund Hørslev-Petersen, Kim Junker, Peter Østergaard, Mikkel Deleuran, Bent Hvid, Malene CXCL13 predicts disease activity in early rheumatoid arthritis and could be an indicator of the therapeutic ‘window of opportunity’ |
title | CXCL13 predicts disease activity in early rheumatoid arthritis and could be an indicator of the therapeutic ‘window of opportunity’ |
title_full | CXCL13 predicts disease activity in early rheumatoid arthritis and could be an indicator of the therapeutic ‘window of opportunity’ |
title_fullStr | CXCL13 predicts disease activity in early rheumatoid arthritis and could be an indicator of the therapeutic ‘window of opportunity’ |
title_full_unstemmed | CXCL13 predicts disease activity in early rheumatoid arthritis and could be an indicator of the therapeutic ‘window of opportunity’ |
title_short | CXCL13 predicts disease activity in early rheumatoid arthritis and could be an indicator of the therapeutic ‘window of opportunity’ |
title_sort | cxcl13 predicts disease activity in early rheumatoid arthritis and could be an indicator of the therapeutic ‘window of opportunity’ |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4201737/ https://www.ncbi.nlm.nih.gov/pubmed/25249397 http://dx.doi.org/10.1186/s13075-014-0434-z |
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