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Estradiol Affects Epstein–Barr Virus Reactivation-Induced Thyrotropin Receptor Antibody and Immunoglobulin Production in Graves’ Disease Patients and Healthy Controls
Epstein–Barr virus (EBV) is a gamma-herpesvirus persisting mainly in human B lymphocytes. EBV reactivation induces host cells to differentiate into plasma cells and is related to autoimmune diseases. Graves’ disease, an autoimmune hyperthyroidism, is caused by the thyrotropin receptor antibody (TRAb...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Mary Ann Liebert, Inc., publishers
2018
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6145039/ https://www.ncbi.nlm.nih.gov/pubmed/30133352 http://dx.doi.org/10.1089/vim.2018.0032 |
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author | Hara, Sayuri Nagata, Keiko Kumata, Keisuke Matsushita, Michiko Kuwamoto, Satoshi Kato, Masako Hayashi, Kazuhiko |
author_facet | Hara, Sayuri Nagata, Keiko Kumata, Keisuke Matsushita, Michiko Kuwamoto, Satoshi Kato, Masako Hayashi, Kazuhiko |
author_sort | Hara, Sayuri |
collection | PubMed |
description | Epstein–Barr virus (EBV) is a gamma-herpesvirus persisting mainly in human B lymphocytes. EBV reactivation induces host cells to differentiate into plasma cells and is related to autoimmune diseases. Graves’ disease, an autoimmune hyperthyroidism, is caused by the thyrotropin receptor antibody (TRAb), which overstimulates thyroid stimulating hormone receptor. The disease occurs predominantly in women, which suggests involvement with estrogen. Graves’ disease patients and healthy controls have EBV-infected lymphocytes with TRAb on the surface (TRAb(+)EBV(+) cells) in peripheral blood mononuclear cells (PBMCs). TRAb can be produced by reactivation of EBV in vitro, which is an alternative system of antibody production. In this study, we cultured PBMCs from Graves’ disease patients and healthy controls with 0, 1, and 100 nM estradiol, corresponding to control, midluteal, and pregnancy levels, respectively, and analyzed the levels of TRAb, total-IgG, and total-IgM during EBV reactivation. We found that 1 nM estradiol increased TRAb levels and 100 nM estradiol slightly lowered them in both patients and controls. In patients, IgM production at 100 nM estradiol was significantly lower than that at 0 nM estradiol (p = 0.028). Estradiol increased the ratio of IgG production to immunoglobulin G (IgG) and immunoglobulin M (IgM) production (IgG/IgG + IgM), which suggested an increase in class switch recombination in the process of EBV reactivation-induced Ig production. Moreover, TRAb production was stimulated by a midluteal level of estradiol and was suppressed by a pregnancy level of estradiol in controls and patients. These results were consistent with premenstrual worsening and maternity improving of autoimmune diseases, including Graves’ disease. |
format | Online Article Text |
id | pubmed-6145039 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Mary Ann Liebert, Inc., publishers |
record_format | MEDLINE/PubMed |
spelling | pubmed-61450392018-09-19 Estradiol Affects Epstein–Barr Virus Reactivation-Induced Thyrotropin Receptor Antibody and Immunoglobulin Production in Graves’ Disease Patients and Healthy Controls Hara, Sayuri Nagata, Keiko Kumata, Keisuke Matsushita, Michiko Kuwamoto, Satoshi Kato, Masako Hayashi, Kazuhiko Viral Immunol Original Articles Epstein–Barr virus (EBV) is a gamma-herpesvirus persisting mainly in human B lymphocytes. EBV reactivation induces host cells to differentiate into plasma cells and is related to autoimmune diseases. Graves’ disease, an autoimmune hyperthyroidism, is caused by the thyrotropin receptor antibody (TRAb), which overstimulates thyroid stimulating hormone receptor. The disease occurs predominantly in women, which suggests involvement with estrogen. Graves’ disease patients and healthy controls have EBV-infected lymphocytes with TRAb on the surface (TRAb(+)EBV(+) cells) in peripheral blood mononuclear cells (PBMCs). TRAb can be produced by reactivation of EBV in vitro, which is an alternative system of antibody production. In this study, we cultured PBMCs from Graves’ disease patients and healthy controls with 0, 1, and 100 nM estradiol, corresponding to control, midluteal, and pregnancy levels, respectively, and analyzed the levels of TRAb, total-IgG, and total-IgM during EBV reactivation. We found that 1 nM estradiol increased TRAb levels and 100 nM estradiol slightly lowered them in both patients and controls. In patients, IgM production at 100 nM estradiol was significantly lower than that at 0 nM estradiol (p = 0.028). Estradiol increased the ratio of IgG production to immunoglobulin G (IgG) and immunoglobulin M (IgM) production (IgG/IgG + IgM), which suggested an increase in class switch recombination in the process of EBV reactivation-induced Ig production. Moreover, TRAb production was stimulated by a midluteal level of estradiol and was suppressed by a pregnancy level of estradiol in controls and patients. These results were consistent with premenstrual worsening and maternity improving of autoimmune diseases, including Graves’ disease. Mary Ann Liebert, Inc., publishers 2018-09-01 2018-09-01 /pmc/articles/PMC6145039/ /pubmed/30133352 http://dx.doi.org/10.1089/vim.2018.0032 Text en © Sayuri Hara et al., 2018; Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms of the Creative Commons Attribution Noncommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are cited. |
spellingShingle | Original Articles Hara, Sayuri Nagata, Keiko Kumata, Keisuke Matsushita, Michiko Kuwamoto, Satoshi Kato, Masako Hayashi, Kazuhiko Estradiol Affects Epstein–Barr Virus Reactivation-Induced Thyrotropin Receptor Antibody and Immunoglobulin Production in Graves’ Disease Patients and Healthy Controls |
title | Estradiol Affects Epstein–Barr Virus Reactivation-Induced Thyrotropin Receptor Antibody and Immunoglobulin Production in Graves’ Disease Patients and Healthy Controls |
title_full | Estradiol Affects Epstein–Barr Virus Reactivation-Induced Thyrotropin Receptor Antibody and Immunoglobulin Production in Graves’ Disease Patients and Healthy Controls |
title_fullStr | Estradiol Affects Epstein–Barr Virus Reactivation-Induced Thyrotropin Receptor Antibody and Immunoglobulin Production in Graves’ Disease Patients and Healthy Controls |
title_full_unstemmed | Estradiol Affects Epstein–Barr Virus Reactivation-Induced Thyrotropin Receptor Antibody and Immunoglobulin Production in Graves’ Disease Patients and Healthy Controls |
title_short | Estradiol Affects Epstein–Barr Virus Reactivation-Induced Thyrotropin Receptor Antibody and Immunoglobulin Production in Graves’ Disease Patients and Healthy Controls |
title_sort | estradiol affects epstein–barr virus reactivation-induced thyrotropin receptor antibody and immunoglobulin production in graves’ disease patients and healthy controls |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6145039/ https://www.ncbi.nlm.nih.gov/pubmed/30133352 http://dx.doi.org/10.1089/vim.2018.0032 |
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