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Regulation of serum matrix metalloproteinases and tissue inhibitor of metalloproteinases-1 following rituximab therapy in patients with rheumatoid arthritis refractory to anti-tumor necrosis factor blockers
In our article, we evaluated the regulatory effects of the infusions of rituximab, a monoclonal antibody directed against CD20(+) B cells, on the serum matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases-1 (TIMP-1) levels in patients with active rheumatoid arthritis (RA) not...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4365285/ https://www.ncbi.nlm.nih.gov/pubmed/25190551 http://dx.doi.org/10.1007/s00296-014-3112-1 |
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author | Klimiuk, Piotr Adrian Domysławska, Izabela Sierakowski, Stanisław Chwiećko, Justyna |
author_facet | Klimiuk, Piotr Adrian Domysławska, Izabela Sierakowski, Stanisław Chwiećko, Justyna |
author_sort | Klimiuk, Piotr Adrian |
collection | PubMed |
description | In our article, we evaluated the regulatory effects of the infusions of rituximab, a monoclonal antibody directed against CD20(+) B cells, on the serum matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases-1 (TIMP-1) levels in patients with active rheumatoid arthritis (RA) not responding to anti-tumor necrosis factor (anti-TNF) therapy. Twelve RA patients were planned to receive four infusions of 1,000 mg of rituximab at weeks 0, 2, 24 and 26. The therapy was combined with methotrexate (MTX) (20–30 mg/week). Seven patients were refractory to previously received infliximab, and five to etanercept. Serum concentrations of interstitial collagenase (MMP-1), stromelysin-1 (MMP-3), gelatinase B (MMP-9) and TIMP-1 were measured by ELISA on weeks 0, 2, 12, 24, 36 and 52. Initial infusion of rituximab downregulated serum MMP-1 (p < 0.01), MMP-3 (p < 0.001), MMP-9 (p < 0.001) and TIMP-1 (p < 0.05) levels. Second drug administration caused even more remarkable reduction of measured MMPs (p < 0.001 in all cases) and TIMP-1 level (p < 0.01). These findings were accompanied by significantly decreased ratios of measured MMPs to TIMP-1. Next rituximab infusions on weeks 24 and 26 sustained the suppression of serum MMPs levels. Prior to the initial rituximab infusion, serum concentrations of studied MMPs and TIMP-1 significantly correlated with markers of RA activity such as disease activity score (DAS28) and CRP levels. Rituximab therapy, beside a rapid clinical improvement, reduced serum MMPs concentrations in RA patients refractory to anti-TNF treatment. Repeated infusions of rituximab maintained initial serum MMPs suppression. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00296-014-3112-1) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4365285 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-43652852015-03-26 Regulation of serum matrix metalloproteinases and tissue inhibitor of metalloproteinases-1 following rituximab therapy in patients with rheumatoid arthritis refractory to anti-tumor necrosis factor blockers Klimiuk, Piotr Adrian Domysławska, Izabela Sierakowski, Stanisław Chwiećko, Justyna Rheumatol Int Original Article - Emerging Hypotheses In our article, we evaluated the regulatory effects of the infusions of rituximab, a monoclonal antibody directed against CD20(+) B cells, on the serum matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases-1 (TIMP-1) levels in patients with active rheumatoid arthritis (RA) not responding to anti-tumor necrosis factor (anti-TNF) therapy. Twelve RA patients were planned to receive four infusions of 1,000 mg of rituximab at weeks 0, 2, 24 and 26. The therapy was combined with methotrexate (MTX) (20–30 mg/week). Seven patients were refractory to previously received infliximab, and five to etanercept. Serum concentrations of interstitial collagenase (MMP-1), stromelysin-1 (MMP-3), gelatinase B (MMP-9) and TIMP-1 were measured by ELISA on weeks 0, 2, 12, 24, 36 and 52. Initial infusion of rituximab downregulated serum MMP-1 (p < 0.01), MMP-3 (p < 0.001), MMP-9 (p < 0.001) and TIMP-1 (p < 0.05) levels. Second drug administration caused even more remarkable reduction of measured MMPs (p < 0.001 in all cases) and TIMP-1 level (p < 0.01). These findings were accompanied by significantly decreased ratios of measured MMPs to TIMP-1. Next rituximab infusions on weeks 24 and 26 sustained the suppression of serum MMPs levels. Prior to the initial rituximab infusion, serum concentrations of studied MMPs and TIMP-1 significantly correlated with markers of RA activity such as disease activity score (DAS28) and CRP levels. Rituximab therapy, beside a rapid clinical improvement, reduced serum MMPs concentrations in RA patients refractory to anti-TNF treatment. Repeated infusions of rituximab maintained initial serum MMPs suppression. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00296-014-3112-1) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2014-09-05 2015 /pmc/articles/PMC4365285/ /pubmed/25190551 http://dx.doi.org/10.1007/s00296-014-3112-1 Text en © The Author(s) 2014 https://creativecommons.org/licenses/by/4.0/ Open AccessThis article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited. |
spellingShingle | Original Article - Emerging Hypotheses Klimiuk, Piotr Adrian Domysławska, Izabela Sierakowski, Stanisław Chwiećko, Justyna Regulation of serum matrix metalloproteinases and tissue inhibitor of metalloproteinases-1 following rituximab therapy in patients with rheumatoid arthritis refractory to anti-tumor necrosis factor blockers |
title | Regulation of serum matrix metalloproteinases and tissue inhibitor of metalloproteinases-1 following rituximab therapy in patients with rheumatoid arthritis refractory to anti-tumor necrosis factor blockers |
title_full | Regulation of serum matrix metalloproteinases and tissue inhibitor of metalloproteinases-1 following rituximab therapy in patients with rheumatoid arthritis refractory to anti-tumor necrosis factor blockers |
title_fullStr | Regulation of serum matrix metalloproteinases and tissue inhibitor of metalloproteinases-1 following rituximab therapy in patients with rheumatoid arthritis refractory to anti-tumor necrosis factor blockers |
title_full_unstemmed | Regulation of serum matrix metalloproteinases and tissue inhibitor of metalloproteinases-1 following rituximab therapy in patients with rheumatoid arthritis refractory to anti-tumor necrosis factor blockers |
title_short | Regulation of serum matrix metalloproteinases and tissue inhibitor of metalloproteinases-1 following rituximab therapy in patients with rheumatoid arthritis refractory to anti-tumor necrosis factor blockers |
title_sort | regulation of serum matrix metalloproteinases and tissue inhibitor of metalloproteinases-1 following rituximab therapy in patients with rheumatoid arthritis refractory to anti-tumor necrosis factor blockers |
topic | Original Article - Emerging Hypotheses |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4365285/ https://www.ncbi.nlm.nih.gov/pubmed/25190551 http://dx.doi.org/10.1007/s00296-014-3112-1 |
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