Estradiol Affects Epstein-Barr Virus Reactivation-Induced Thyrotropin Receptor Antibody and Immunoglobulin Production in Graves' Disease Patients and Healthy Controls.
Estradiol Affects Epstein-Barr Virus Reactivation-Induced Thyrotropin Receptor Antibody and Immunoglobulin Production in Graves' Disease Patients and Healthy Controls.
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DOI：
10.1089/vim.2018.0032
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发表时间：
2018-09
期刊：
影响因子：
2.2
通讯作者：
Hayashi K
中科院分区：
文献类型：
--
作者：
Hara S;Nagata K;Kumata K;Matsushita M;Kuwamoto S;Kato M;Hayashi K
EB病毒（Epstein-Barr virus，EBV）是一种主要存在于人类B淋巴细胞中的γ-疱疹病毒。EBV再活化诱导宿主细胞分化为浆细胞，并与自身免疫性疾病有关。Graves病是一种自身免疫性甲状腺功能亢进症，由促甲状腺激素受体抗体（TRAb）过度刺激促甲状腺激素受体引起。这种疾病主要发生在女性，这表明与雌激素有关。Graves病患者和健康对照者外周血单核细胞（PBMC）中存在表面具有TRAb的EBV感染淋巴细胞（TRAb（+）EBV（+）细胞）。TRAb可以通过体外再活化EBV产生，这是抗体产生的替代系统。在这项研究中，我们培养的PBMC从格雷夫斯病患者和健康对照与0，1，和100 nM雌二醇，分别对应于控制，黄体中期，和妊娠水平，并分析了在EBV再激活的TRAb，总IgG和总IgM的水平。我们发现，在患者和对照组中，1 nM雌二醇增加TRAb水平，100 nM雌二醇略微降低TRAb水平。在患者中，100 nM雌二醇时IgM的产生显著低于0 nM雌二醇（p = 0.028）。EB病毒激活后，IgG与IgG、IgM的比值（IgG/IgG + IgM）增加，提示EB病毒激活诱导的IG产生过程中，类转换重组增加。此外，TRAb的产生刺激黄体中期水平的雌二醇和抑制妊娠水平的雌二醇在控制和患者。这些结果与自身免疫性疾病（包括Graves病）的经前恶化和产妇改善一致。
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.
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影响因子：
2.2
作者：
Nagata K;Kumata K;Nakayama Y;Satoh Y;Sugihara H;Hara S;Matsushita M;Kuwamoto S;Kato M;Murakami I;Hayashi K
通讯作者：
Hayashi K
影响因子：
3.5
作者：
Nagata K;Higaki K;Nakayama Y;Miyauchi H;Kiritani Y;Kanai K;Matsushita M;Iwasaki T;Sugihara H;Kuwamoto S;Kato M;Murakami I;Nanba E;Kimura H;Hayashi K
通讯作者：
Hayashi K
影响因子：
7.4
作者：
Allred, DC;Brown, P;Medina, D
通讯作者：
Medina, D
影响因子：
168.9
作者：
Davies, C.;Godwin, J.;Gray, R.;Clarke, M.;Darby, S.;McGale, P.;Wang, Y. C.;Peto, R.;Pan, H. C.;Cutter, D.;Taylor, C.;Ingle, J.
通讯作者：
Ingle, J.
影响因子：
3.6
作者：
Jones, Bart G.;Penkert, Rhiannon R.;Hurwitz, Julia L.
通讯作者：
Hurwitz, Julia L.