Presence of Epstein-Barr virus-infected B lymphocytes with thyrotropin receptor antibodies on their surface in Graves' disease patients and in healthy individuals.
Presence of Epstein-Barr virus-infected B lymphocytes with thyrotropin receptor antibodies on their surface in Graves' disease patients and in healthy individuals.
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DOI：
10.3109/08916934.2013.879863
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发表时间：
2014-05
期刊：
影响因子：
3.5
通讯作者：
Hayashi K
中科院分区：
文献类型：
--
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
Graves病是由促甲状腺激素受体抗体（TRAb）引起的自身免疫性甲状腺功能亢进症。由于EB病毒（EBV）持续存在于B细胞中，并偶尔被重新激活，我们假设EBV通过刺激TRAb产生的B细胞而促进Graves病患者的TRAb产生。为了使EBV刺激抗体产生细胞，EBV必须存在于那些细胞中，但尚未观察到。我们检测了Graves病患者外周血中是否存在EBV感染的（EBV（+））B细胞，其表面有TRAb（+）作为膜免疫球蛋白。采用流式细胞术和激光共聚焦显微镜对13例患者和11例健康对照者的培养或未培养的外周血单个核细胞（PBMCs）进行分析，证实8例患者的培养PBMCs均为TRAbs（+）EBV（+）双阳性细胞。我们意外地在所有健康对照中检测到TRAb（+）细胞，并且在来自八个健康对照的所有培养的PBMC中检测到TRAb（+）EBV（+）双阳性细胞。患者培养的PBMC中TRAb（+）细胞的频率显著高于对照组（p = 0.021）。在这项研究中，我们指出存在的EBV感染的B淋巴细胞与TRAb在其表面上，一个可能的球员的生产过量TRAb，致病性自身抗体的格雷夫斯病。这是我们假设EBV有助于Graves病患者TRAb产生的基本证据。我们的研究结果进一步表明，健康对照具有TRAbs生产的潜力。这为我们深入了解Graves病的发病机制提供了重要线索。
Graves’ disease is an autoimmune hyperthyroidism caused by thyrotropin receptor antibodies (TRAbs). Because Epstein–Barr virus (EBV) persists in B cells and is occasionally reactivated, we hypothesized that EBV contributes to TRAbs production in Graves’ disease patients by stimulating the TRAbs-producing B cells. In order for EBV to stimulate antibody-producing cells, EBV must be present in those cells but that have not yet been observed. We examined whether EBV-infected (EBV(+)) B cells with TRAbs on their surface (TRAbs(+)) as membrane immunoglobulin were present in peripheral blood of Graves’ disease patients. We analyzed cultured or non-cultured peripheral blood mononuclear cells (PBMCs) from 13 patients and 11 healthy controls by flow-cytometry and confocal laser microscopy, and confirmed all cultured PBMCs from 8 patients really had TRAbs(+) EBV(+) double positive cells. We unexpectedly detected TRAbs(+) cells in all healthy controls, and TRAbs(+) EBV(+) double positive cells in all cultured PBMC from eight healthy controls. The frequency of TRAbs(+) cells in cultured PBMCs was significantly higher in patients than in controls (p = 0.021). In this study, we indicated the presence of EBV-infected B lymphocytes with TRAbs on their surface, a possible player of the production of excessive TRAbs, the causative autoantibody for Graves’ disease. This is a basic evidence for our hypothesis that EBV contributes to TRAbs production in Graves’ disease patients. Our results further suggest that healthy controls have the potential for TRAbs production. This gives us an important insight into the pathogenesis of Graves’ disease.