Activation of thyroid antigen-reactive B cells in recent onset autoimmune thyroid disease patients.

Activation of thyroid antigen-reactive B cells in recent onset autoimmune thyroid disease patients.
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DOI:
10.1016/j.jaut.2017.12.001
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发表时间:
2018-05
影响因子:
12.8
通讯作者:
Cambier JC
Cambier JC
中科院分区:
医学1区
文献类型:
--
作者:
Smith MJ;Rihanek M;Coleman BM;Gottlieb PA;Sarapura VD;Cambier JC

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自身免疫性甲状腺疾病(AITD),包括桥本甲状腺炎(HT)和格雷夫斯病(GD),是美国最常见的自身免疫性疾病,影响超过2000万人。在诊断时,HT和GD的特征都是甲状腺中B淋巴细胞和T淋巴细胞的积聚以及针对甲状腺的自身抗体的产生,这表明自身反应性淋巴细胞的耐受性已被打破。然而,很少有研究试图了解AITD最终导致自身抗体产生和甲状腺功能丧失的潜在发病机制。在这项研究中,我们分析了新发和长期AITD患者外周血中甲状腺抗原反应性B细胞的表型。我们发现,在新发患者中,血液中的甲状腺抗原反应性B细胞不再表现为无反应性,而是表达激活标志物CD86。这可能反映了这些细胞的激活导致了自身抗体的产生。因此,这项研究报告了甲状腺抗原反应性B细胞无反应性的早期丧失,这一事件有助于AITD的发展。
Autoimmune thyroid disease (AITD), including Hashimoto’s thyroiditis (HT) and Graves’ disease (GD), is the most common autoimmune disorder in the United States, affecting over 20 million people. At the time of diagnosis, both HD and GD are characterized by the accumulation of B and T lymphocytes in the thyroid gland and production of autoantibodies targeting the thyroid, indicating that a breach in tolerance of autoreactive lymphocytes has occurred. However, few studies have sought to understand the underlying pathogenesis of AITD that ultimately leads to production of autoantibodies and loss of thyroid function. In this study, we analyzed the phenotype of thyroid antigen-reactive B cells in the peripheral blood of recent onset and long standing AITD patients. We found that in recent onset patients thyroid antigen-reactive B cells in blood no longer appear anergic, rather they express CD86, a marker of activation. This likely reflects activation of these cells leading to their production of autoantibodies. Hence, this study reports the early loss of anergy in thyroid antigen-reactive B cells, an event that contributes to development of AITD.
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