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Circulating anti-citrullinated peptide antibodies, cytokines and genotype as biomarkers of response to disease-modifying antirheumatic drug therapy in early rheumatoid arthritis
BACKGROUND: To measure circulating anti-citrullinated peptide antibodies (ACPA) and cytokines pre- and 6 months post-therapy as a strategy to predict and optimize responses to traditional disease-modifying antirheumatic drugs (DMARDs) in early RA, which is an unmet need in developing countries. PATI...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4446850/ https://www.ncbi.nlm.nih.gov/pubmed/26021985 http://dx.doi.org/10.1186/s12891-015-0587-1 |
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author | Ally, Mahmood M. T. M. Hodkinson, Bridget Meyer, Pieter W. A. Musenge, Eustasius Tintinger, Gregory R. Tikly, Mohammed Anderson, Ronald |
author_facet | Ally, Mahmood M. T. M. Hodkinson, Bridget Meyer, Pieter W. A. Musenge, Eustasius Tintinger, Gregory R. Tikly, Mohammed Anderson, Ronald |
author_sort | Ally, Mahmood M. T. M. |
collection | PubMed |
description | BACKGROUND: To measure circulating anti-citrullinated peptide antibodies (ACPA) and cytokines pre- and 6 months post-therapy as a strategy to predict and optimize responses to traditional disease-modifying antirheumatic drugs (DMARDs) in early RA, which is an unmet need in developing countries. PATIENTS AND METHODS: A cohort of 140 predominantly (88.5 %) black female South African patients with early RA was treated with synthetic DMARDs, mostly methotrexate (MTX) alone, or in combination with low-dose oral corticosteroids (CS). Circulating ACPA and a panel of circulating cytokines/chemokines/growth factors were measured at baseline and after 6 months of therapy in relation to disease activity and Shared Epitope (SE). RESULTS: Following 6 months of therapy, the median simplified disease activity index (SDAI) declined from a baseline of 41.4 to 16.0 (p = 0.0001) for the entire cohort, which was paralleled by significant falls in median serum ACPA levels (516.6 vs. 255.7 units/ml, p = <0.0001) and several of the circulating cytokines (IL-4, IL-7, IL-8, G-CSF, VEGF; p < 0.0010 – p < 0.0001) which were most evident in the subgroup of patients treated with a combination of MTX and CS. Although biomarker concentrations decreased most notably in the low-disease activity group post-therapy, no significant correlations between these biomarkers and disease activity were observed, Baseline ACPA levels, but not SDAI or cytokines, were significantly higher in the subgroup of risk allele-positive patients (561.1 vs. 331.9 units/ml, p < 0.05), while no associations with ACPA and a smoking history were evident. CONCLUSIONS: The use of DMARDs in RA is associated with significant decreases in ACPA and cytokines which did not correlate with changes in SDAI, precluding the utility of serial measurement of these biomarkers to monitor early responses to therapy, but may have prognostic value. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12891-015-0587-1) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4446850 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-44468502015-05-29 Circulating anti-citrullinated peptide antibodies, cytokines and genotype as biomarkers of response to disease-modifying antirheumatic drug therapy in early rheumatoid arthritis Ally, Mahmood M. T. M. Hodkinson, Bridget Meyer, Pieter W. A. Musenge, Eustasius Tintinger, Gregory R. Tikly, Mohammed Anderson, Ronald BMC Musculoskelet Disord Research Article BACKGROUND: To measure circulating anti-citrullinated peptide antibodies (ACPA) and cytokines pre- and 6 months post-therapy as a strategy to predict and optimize responses to traditional disease-modifying antirheumatic drugs (DMARDs) in early RA, which is an unmet need in developing countries. PATIENTS AND METHODS: A cohort of 140 predominantly (88.5 %) black female South African patients with early RA was treated with synthetic DMARDs, mostly methotrexate (MTX) alone, or in combination with low-dose oral corticosteroids (CS). Circulating ACPA and a panel of circulating cytokines/chemokines/growth factors were measured at baseline and after 6 months of therapy in relation to disease activity and Shared Epitope (SE). RESULTS: Following 6 months of therapy, the median simplified disease activity index (SDAI) declined from a baseline of 41.4 to 16.0 (p = 0.0001) for the entire cohort, which was paralleled by significant falls in median serum ACPA levels (516.6 vs. 255.7 units/ml, p = <0.0001) and several of the circulating cytokines (IL-4, IL-7, IL-8, G-CSF, VEGF; p < 0.0010 – p < 0.0001) which were most evident in the subgroup of patients treated with a combination of MTX and CS. Although biomarker concentrations decreased most notably in the low-disease activity group post-therapy, no significant correlations between these biomarkers and disease activity were observed, Baseline ACPA levels, but not SDAI or cytokines, were significantly higher in the subgroup of risk allele-positive patients (561.1 vs. 331.9 units/ml, p < 0.05), while no associations with ACPA and a smoking history were evident. CONCLUSIONS: The use of DMARDs in RA is associated with significant decreases in ACPA and cytokines which did not correlate with changes in SDAI, precluding the utility of serial measurement of these biomarkers to monitor early responses to therapy, but may have prognostic value. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12891-015-0587-1) contains supplementary material, which is available to authorized users. BioMed Central 2015-05-29 /pmc/articles/PMC4446850/ /pubmed/26021985 http://dx.doi.org/10.1186/s12891-015-0587-1 Text en © Ally et al.; licensee BioMed Central. 2015 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 credited. 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 Ally, Mahmood M. T. M. Hodkinson, Bridget Meyer, Pieter W. A. Musenge, Eustasius Tintinger, Gregory R. Tikly, Mohammed Anderson, Ronald Circulating anti-citrullinated peptide antibodies, cytokines and genotype as biomarkers of response to disease-modifying antirheumatic drug therapy in early rheumatoid arthritis |
title | Circulating anti-citrullinated peptide antibodies, cytokines and genotype as biomarkers of response to disease-modifying antirheumatic drug therapy in early rheumatoid arthritis |
title_full | Circulating anti-citrullinated peptide antibodies, cytokines and genotype as biomarkers of response to disease-modifying antirheumatic drug therapy in early rheumatoid arthritis |
title_fullStr | Circulating anti-citrullinated peptide antibodies, cytokines and genotype as biomarkers of response to disease-modifying antirheumatic drug therapy in early rheumatoid arthritis |
title_full_unstemmed | Circulating anti-citrullinated peptide antibodies, cytokines and genotype as biomarkers of response to disease-modifying antirheumatic drug therapy in early rheumatoid arthritis |
title_short | Circulating anti-citrullinated peptide antibodies, cytokines and genotype as biomarkers of response to disease-modifying antirheumatic drug therapy in early rheumatoid arthritis |
title_sort | circulating anti-citrullinated peptide antibodies, cytokines and genotype as biomarkers of response to disease-modifying antirheumatic drug therapy in early rheumatoid arthritis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4446850/ https://www.ncbi.nlm.nih.gov/pubmed/26021985 http://dx.doi.org/10.1186/s12891-015-0587-1 |
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