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FK506 attenuates thymic output in patients with myasthenia gravis
INTRODUCTION: Myasthenia gravis (MG) is an antibody-mediated, T-cell-dependent autoimmune disease. The symptoms are caused by high-affinity IgG against the muscle acetylcholine receptor (AChR) at the neuromuscular junction. The production of these antibodies in B-cells depends on AChR-specific CD4(+...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Termedia Publishing House
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3902727/ https://www.ncbi.nlm.nih.gov/pubmed/24482655 http://dx.doi.org/10.5114/aoms.2013.39797 |
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author | Mitsui, Takao Kuroda, Yukiko Ueno, Shu-ichi Matsui, Naoko Kaji, Ryuji |
author_facet | Mitsui, Takao Kuroda, Yukiko Ueno, Shu-ichi Matsui, Naoko Kaji, Ryuji |
author_sort | Mitsui, Takao |
collection | PubMed |
description | INTRODUCTION: Myasthenia gravis (MG) is an antibody-mediated, T-cell-dependent autoimmune disease. The symptoms are caused by high-affinity IgG against the muscle acetylcholine receptor (AChR) at the neuromuscular junction. The production of these antibodies in B-cells depends on AChR-specific CD4(+) T-cells and the thymus gland seems to play a significant role in the pathogenesis of MG. Altered thymic T-cell export seems to be associated with a pathological mechanism in myasthenia gravis. Tacrolimus (FK506) has recently been used to treat MG. MATERIAL AND METHODS: We examined the effects of tacrolimus on thymic T-cell export in patients with MG. Sixteen patients with nonthymomatous and/or thymectomized MG were treated with oral administrations of tacrolimus. To assess the effect of tacrolimus on the thymic output, we assayed the levels of T-cell receptor excision circle (TREC), a molecular marker of thymus emigrants. RESULTS: T-cell receptor excision circle was not significantly different from those in age-matched controls before tacrolimus therapy, but they were partially decreased 4 months after tacrolimus therapy. T-cell receptor excision circle levels were significantly decreased in the thymomatous group (p < 0.05), but not in the nonthymomatous group. Tacrolimus treatment significantly attenuated TREC levels in cultured CD4(–)CD8(+) cells (p < 0.05), but total cell counts were not significantly changed. CONCLUSIONS: These results indicate that TREC levels may become a marker of the curative effect of tacrolimus therapy for thymomatous MG, and that tacrolimus suppresses not only activating T-lymphocytes, but also naïve T-cells. |
format | Online Article Text |
id | pubmed-3902727 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Termedia Publishing House |
record_format | MEDLINE/PubMed |
spelling | pubmed-39027272014-01-30 FK506 attenuates thymic output in patients with myasthenia gravis Mitsui, Takao Kuroda, Yukiko Ueno, Shu-ichi Matsui, Naoko Kaji, Ryuji Arch Med Sci Clinical Research INTRODUCTION: Myasthenia gravis (MG) is an antibody-mediated, T-cell-dependent autoimmune disease. The symptoms are caused by high-affinity IgG against the muscle acetylcholine receptor (AChR) at the neuromuscular junction. The production of these antibodies in B-cells depends on AChR-specific CD4(+) T-cells and the thymus gland seems to play a significant role in the pathogenesis of MG. Altered thymic T-cell export seems to be associated with a pathological mechanism in myasthenia gravis. Tacrolimus (FK506) has recently been used to treat MG. MATERIAL AND METHODS: We examined the effects of tacrolimus on thymic T-cell export in patients with MG. Sixteen patients with nonthymomatous and/or thymectomized MG were treated with oral administrations of tacrolimus. To assess the effect of tacrolimus on the thymic output, we assayed the levels of T-cell receptor excision circle (TREC), a molecular marker of thymus emigrants. RESULTS: T-cell receptor excision circle was not significantly different from those in age-matched controls before tacrolimus therapy, but they were partially decreased 4 months after tacrolimus therapy. T-cell receptor excision circle levels were significantly decreased in the thymomatous group (p < 0.05), but not in the nonthymomatous group. Tacrolimus treatment significantly attenuated TREC levels in cultured CD4(–)CD8(+) cells (p < 0.05), but total cell counts were not significantly changed. CONCLUSIONS: These results indicate that TREC levels may become a marker of the curative effect of tacrolimus therapy for thymomatous MG, and that tacrolimus suppresses not only activating T-lymphocytes, but also naïve T-cells. Termedia Publishing House 2013-12-26 2013-12-30 /pmc/articles/PMC3902727/ /pubmed/24482655 http://dx.doi.org/10.5114/aoms.2013.39797 Text en Copyright © 2013 Termedia & Banach http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-Noncommercial 3.0 Unported License, permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Clinical Research Mitsui, Takao Kuroda, Yukiko Ueno, Shu-ichi Matsui, Naoko Kaji, Ryuji FK506 attenuates thymic output in patients with myasthenia gravis |
title | FK506 attenuates thymic output in patients with myasthenia gravis |
title_full | FK506 attenuates thymic output in patients with myasthenia gravis |
title_fullStr | FK506 attenuates thymic output in patients with myasthenia gravis |
title_full_unstemmed | FK506 attenuates thymic output in patients with myasthenia gravis |
title_short | FK506 attenuates thymic output in patients with myasthenia gravis |
title_sort | fk506 attenuates thymic output in patients with myasthenia gravis |
topic | Clinical Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3902727/ https://www.ncbi.nlm.nih.gov/pubmed/24482655 http://dx.doi.org/10.5114/aoms.2013.39797 |
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