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甲状腺蛋白受体抗体反应组决定了甲状腺和逆轨道反应能力
Pingping Xiang1, Rauf Latif1,2, Terry F Davies1,2
1Thyroid Research Unit, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
概括
这项研究开发了Graves病小鼠模型,发现虽然所有小鼠都产生了TSHR抗体,但只有56%的小鼠患有甲状腺功能障碍. 刺激和阻断抗体的平衡影响了甲状腺结果.
科学领域:
- 内分泌学 在内分泌学.
- 免疫学 免疫学 免疫学
- 翻译医学是一种翻译医学.
背景情况:
- 在格雷夫斯病 (GD) 和甲状腺眼病 (TED) 中不同甲状腺激素 (TSH) 受体 (TSHR) 抗体的作用尚未完全理解.
- 现有的动物模型往往无法复制人类GD和TED的复杂性,忽视了完整的TSHR反应体.
研究的目的:
- 评估一种用于格雷夫斯病 (GD) 的新型小鼠模型,重点关注具有不同生物活性的TSHR抗体.
- 在小鼠模型中研究不同类型的TSHR抗体对甲状腺功能和轨道变化的影响.
主要方法:
- 雌性Balb/c小鼠用表达人类TSHR残留物1-289.9的腺病毒接种免疫.
- 用T4和TSH水平评估甲状腺功能;用基于细胞的测定测量抗体生物活性 (TSAb,TBAb).
- 在30周后,使用超声波,微MRI和组织学分析了甲状腺和轨道组织.
主要成果:
- 56% (9/16) 的小鼠患有甲状腺功能障碍,其特征是T4升高和TSH水平降低,甲状腺扩大.
- 所有小鼠都产生了TSHR抗体;甲状腺功能高的小鼠主要具有低水平的TSHR刺激抗体 (TSAb),以及阻断TSHR抗体 (TBAb).
- 五只甲状腺过高的小鼠表现出轻微的眼睛症状,微MRI和组织学显示了 retrobulbar组织变化和巨细胞透.
结论:
- 该研究强调,在这种GD模型中,开发TSHR抗体并不能保证甲状腺功能升高.
- 在确定甲状腺结局方面,TSAb和TBAb活性之间的平衡似乎至关重要,TBAb有可能减轻甲状腺功能障碍.
- 这种模型强调了评估完整的TSHR抗体反应体对理解GD病原学的重要性.
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