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The balance between Foxp3 and Ror-γt expression in peripheral blood is altered by tocilizumab and abatacept in patients with rheumatoid arthritis

BACKGROUND: The balance between Th17 cells and regulatory T (Treg) cells has been shown to play an important role in the development of rheumatoid arthritis (RA). Recent studies have shown that treatment with abatacept (ABT) or tocilizumab (TCZ) affects Th17 and Treg cell populations. Although not u...

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Autores principales: Tada, Yoshifumi, Ono, Nobuyuki, Suematsu, Rie, Tashiro, Satoko, Sadanaga, Yuri, Tokuda, Yukiko, Ono, Yukihide, Nakao, Yoshinobu, Maruyama, Akihito, Ohta, Akihide, Koarada, Syuichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4947268/
https://www.ncbi.nlm.nih.gov/pubmed/27421886
http://dx.doi.org/10.1186/s12891-016-1137-1
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author Tada, Yoshifumi
Ono, Nobuyuki
Suematsu, Rie
Tashiro, Satoko
Sadanaga, Yuri
Tokuda, Yukiko
Ono, Yukihide
Nakao, Yoshinobu
Maruyama, Akihito
Ohta, Akihide
Koarada, Syuichi
author_facet Tada, Yoshifumi
Ono, Nobuyuki
Suematsu, Rie
Tashiro, Satoko
Sadanaga, Yuri
Tokuda, Yukiko
Ono, Yukihide
Nakao, Yoshinobu
Maruyama, Akihito
Ohta, Akihide
Koarada, Syuichi
author_sort Tada, Yoshifumi
collection PubMed
description BACKGROUND: The balance between Th17 cells and regulatory T (Treg) cells has been shown to play an important role in the development of rheumatoid arthritis (RA). Recent studies have shown that treatment with abatacept (ABT) or tocilizumab (TCZ) affects Th17 and Treg cell populations. Although not unanimously accepted, several reports have shown that Treg cells are decreased by ABT and increased by TCZ, and that Th17 cells are decreased by TCZ. To further investigate the effects of ABT and TCZ on the skewing of T cell populations, we analyzed the expression of master regulators genes of helper T cell lineages following ABT/TCZ treatment of RA patients. METHODS: Ten patients treated with ABT and 10 patients treated with TCZ were enrolled. Total RNA was extracted from peripheral blood cells at baseline, and after 12 and 24 weeks of therapy. The expression levels of T-bet, GATA3, Foxp3 and Ror-γt were semi-quantified using real-time PCR. The relative expression levels were expressed as the ratios of two genes (T-bet/GATA3, Foxp3/GATA3, Foxp3/T-bet, Foxp3/Ror-γt, Ror-γt/T-bet, Ror-γt/GATA3), and the changes in these ratios with treatment were determined. RESULTS: The Foxp3/Ror-γt ratio was decreased after ABT therapy (0.67 ± 0.16 at 24 weeks, P = 0.0034) but was increased after TCZ therapy (2.00 ± 1.03 at 24 weeks, P = 0.0013). In addition, the Ror-γt/GATA3 ratio was decreased after TCZ therapy (0.78 ± 0.37 at 24 weeks, P = 0.0008). Except for these ratios, no significant skewing in the expression of these factors was detected. No significant relationship between clinical response to the treatment and change in the ratios of these factors was determined. CONCLUSION: Treatment with TCZ or ABT differently affected the balance between Foxp3 and Ror-γt expression in the peripheral blood of patients with RA. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12891-016-1137-1) contains supplementary material, which is available to authorized users.
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spelling pubmed-49472682016-07-17 The balance between Foxp3 and Ror-γt expression in peripheral blood is altered by tocilizumab and abatacept in patients with rheumatoid arthritis Tada, Yoshifumi Ono, Nobuyuki Suematsu, Rie Tashiro, Satoko Sadanaga, Yuri Tokuda, Yukiko Ono, Yukihide Nakao, Yoshinobu Maruyama, Akihito Ohta, Akihide Koarada, Syuichi BMC Musculoskelet Disord Research Article BACKGROUND: The balance between Th17 cells and regulatory T (Treg) cells has been shown to play an important role in the development of rheumatoid arthritis (RA). Recent studies have shown that treatment with abatacept (ABT) or tocilizumab (TCZ) affects Th17 and Treg cell populations. Although not unanimously accepted, several reports have shown that Treg cells are decreased by ABT and increased by TCZ, and that Th17 cells are decreased by TCZ. To further investigate the effects of ABT and TCZ on the skewing of T cell populations, we analyzed the expression of master regulators genes of helper T cell lineages following ABT/TCZ treatment of RA patients. METHODS: Ten patients treated with ABT and 10 patients treated with TCZ were enrolled. Total RNA was extracted from peripheral blood cells at baseline, and after 12 and 24 weeks of therapy. The expression levels of T-bet, GATA3, Foxp3 and Ror-γt were semi-quantified using real-time PCR. The relative expression levels were expressed as the ratios of two genes (T-bet/GATA3, Foxp3/GATA3, Foxp3/T-bet, Foxp3/Ror-γt, Ror-γt/T-bet, Ror-γt/GATA3), and the changes in these ratios with treatment were determined. RESULTS: The Foxp3/Ror-γt ratio was decreased after ABT therapy (0.67 ± 0.16 at 24 weeks, P = 0.0034) but was increased after TCZ therapy (2.00 ± 1.03 at 24 weeks, P = 0.0013). In addition, the Ror-γt/GATA3 ratio was decreased after TCZ therapy (0.78 ± 0.37 at 24 weeks, P = 0.0008). Except for these ratios, no significant skewing in the expression of these factors was detected. No significant relationship between clinical response to the treatment and change in the ratios of these factors was determined. CONCLUSION: Treatment with TCZ or ABT differently affected the balance between Foxp3 and Ror-γt expression in the peripheral blood of patients with RA. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12891-016-1137-1) contains supplementary material, which is available to authorized users. BioMed Central 2016-07-16 /pmc/articles/PMC4947268/ /pubmed/27421886 http://dx.doi.org/10.1186/s12891-016-1137-1 Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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
Tada, Yoshifumi
Ono, Nobuyuki
Suematsu, Rie
Tashiro, Satoko
Sadanaga, Yuri
Tokuda, Yukiko
Ono, Yukihide
Nakao, Yoshinobu
Maruyama, Akihito
Ohta, Akihide
Koarada, Syuichi
The balance between Foxp3 and Ror-γt expression in peripheral blood is altered by tocilizumab and abatacept in patients with rheumatoid arthritis
title The balance between Foxp3 and Ror-γt expression in peripheral blood is altered by tocilizumab and abatacept in patients with rheumatoid arthritis
title_full The balance between Foxp3 and Ror-γt expression in peripheral blood is altered by tocilizumab and abatacept in patients with rheumatoid arthritis
title_fullStr The balance between Foxp3 and Ror-γt expression in peripheral blood is altered by tocilizumab and abatacept in patients with rheumatoid arthritis
title_full_unstemmed The balance between Foxp3 and Ror-γt expression in peripheral blood is altered by tocilizumab and abatacept in patients with rheumatoid arthritis
title_short The balance between Foxp3 and Ror-γt expression in peripheral blood is altered by tocilizumab and abatacept in patients with rheumatoid arthritis
title_sort balance between foxp3 and ror-γt expression in peripheral blood is altered by tocilizumab and abatacept in patients with rheumatoid arthritis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4947268/
https://www.ncbi.nlm.nih.gov/pubmed/27421886
http://dx.doi.org/10.1186/s12891-016-1137-1
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