The Impact of DMARD and Anti-TNF Therapy on Functional Characterization of Short-Term T-Cell Activation in Patients with Rheumatoid Arthritis – A Follow-Up Study
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by a systemic dysfunction of T-cells. In this study we tested the impact of DMARD and anti-TNF agents on short-term activation characteristics of T-cells. We enrolled 12 patients with newly diagnosed RA (naïve RA) who were treat...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2014
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4123936/ https://www.ncbi.nlm.nih.gov/pubmed/25098248 http://dx.doi.org/10.1371/journal.pone.0104298 |
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author | Szalay, Balázs Cseh, Áron Mészáros, Gergő Kovács, László Balog, Attila Vásárhelyi, Barna |
author_facet | Szalay, Balázs Cseh, Áron Mészáros, Gergő Kovács, László Balog, Attila Vásárhelyi, Barna |
author_sort | Szalay, Balázs |
collection | PubMed |
description | Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by a systemic dysfunction of T-cells. In this study we tested the impact of DMARD and anti-TNF agents on short-term activation characteristics of T-cells. We enrolled 12 patients with newly diagnosed RA (naïve RA) who were treated with methothrexate (MTX) and glucocorticsteroid (GCS) and 22 patients with established RA non responding to conventional DMARD therapy who were treated with different anti-TNF agents. Nine healthy volunteers served as controls. Blood samples were taken at baseline, then at 4(th) and 8(th) week of therapy. The characteristics of several intracellular activation processes during short-term activation of T-cells including cytoplasmic Ca(2+) level, mitochondrial Ca(2+) level, reactive oxygen species (ROS) and nitric oxide (NO) generation were determined by a novel flow-cytometry technique. At baseline, the tested processes were comparable to controls in naïve RA. During GCS therapy, cytoplasmic Ca(2+) level and ROS generation decreased. After the addition of MTX to GCS cytoplasmic Ca(2+) level became comparable to controls, while ROS generation decreased further. In DMARD non responders, cytoplasmic Ca(2+) level was higher than controls at baseline. The cytoplasmic Ca(2+) level became comparable to controls and ROS generation decreased during each of the three anti-TNF-α agent therapies. Mitochondrial Ca(2+) level and NO generation were unaltered in all of the patient groups. These results indicate that intracellular machinery is affected in T-cells of RA patients. This may alter the behavior of T-cells during activation. Different therapeutic approaches may modulate the abnormal T-cell functions. |
format | Online Article Text |
id | pubmed-4123936 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-41239362014-08-12 The Impact of DMARD and Anti-TNF Therapy on Functional Characterization of Short-Term T-Cell Activation in Patients with Rheumatoid Arthritis – A Follow-Up Study Szalay, Balázs Cseh, Áron Mészáros, Gergő Kovács, László Balog, Attila Vásárhelyi, Barna PLoS One Research Article Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by a systemic dysfunction of T-cells. In this study we tested the impact of DMARD and anti-TNF agents on short-term activation characteristics of T-cells. We enrolled 12 patients with newly diagnosed RA (naïve RA) who were treated with methothrexate (MTX) and glucocorticsteroid (GCS) and 22 patients with established RA non responding to conventional DMARD therapy who were treated with different anti-TNF agents. Nine healthy volunteers served as controls. Blood samples were taken at baseline, then at 4(th) and 8(th) week of therapy. The characteristics of several intracellular activation processes during short-term activation of T-cells including cytoplasmic Ca(2+) level, mitochondrial Ca(2+) level, reactive oxygen species (ROS) and nitric oxide (NO) generation were determined by a novel flow-cytometry technique. At baseline, the tested processes were comparable to controls in naïve RA. During GCS therapy, cytoplasmic Ca(2+) level and ROS generation decreased. After the addition of MTX to GCS cytoplasmic Ca(2+) level became comparable to controls, while ROS generation decreased further. In DMARD non responders, cytoplasmic Ca(2+) level was higher than controls at baseline. The cytoplasmic Ca(2+) level became comparable to controls and ROS generation decreased during each of the three anti-TNF-α agent therapies. Mitochondrial Ca(2+) level and NO generation were unaltered in all of the patient groups. These results indicate that intracellular machinery is affected in T-cells of RA patients. This may alter the behavior of T-cells during activation. Different therapeutic approaches may modulate the abnormal T-cell functions. Public Library of Science 2014-08-06 /pmc/articles/PMC4123936/ /pubmed/25098248 http://dx.doi.org/10.1371/journal.pone.0104298 Text en © 2014 Szalay et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Szalay, Balázs Cseh, Áron Mészáros, Gergő Kovács, László Balog, Attila Vásárhelyi, Barna The Impact of DMARD and Anti-TNF Therapy on Functional Characterization of Short-Term T-Cell Activation in Patients with Rheumatoid Arthritis – A Follow-Up Study |
title | The Impact of DMARD and Anti-TNF Therapy on Functional Characterization of Short-Term T-Cell Activation in Patients with Rheumatoid Arthritis – A Follow-Up Study |
title_full | The Impact of DMARD and Anti-TNF Therapy on Functional Characterization of Short-Term T-Cell Activation in Patients with Rheumatoid Arthritis – A Follow-Up Study |
title_fullStr | The Impact of DMARD and Anti-TNF Therapy on Functional Characterization of Short-Term T-Cell Activation in Patients with Rheumatoid Arthritis – A Follow-Up Study |
title_full_unstemmed | The Impact of DMARD and Anti-TNF Therapy on Functional Characterization of Short-Term T-Cell Activation in Patients with Rheumatoid Arthritis – A Follow-Up Study |
title_short | The Impact of DMARD and Anti-TNF Therapy on Functional Characterization of Short-Term T-Cell Activation in Patients with Rheumatoid Arthritis – A Follow-Up Study |
title_sort | impact of dmard and anti-tnf therapy on functional characterization of short-term t-cell activation in patients with rheumatoid arthritis – a follow-up study |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4123936/ https://www.ncbi.nlm.nih.gov/pubmed/25098248 http://dx.doi.org/10.1371/journal.pone.0104298 |
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