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个体肌痛性骨髓灰质炎自身抗体克隆可以有效地调解多种病理机制
Minh C Pham1, Gianvito Masi1,2, Rosa Patzina1,2
1Department of Immunobiology, Yale University School of Medicine, 300 George Street-Room 353J, New Haven, CT, 06511, USA.
Acta neuropathologica
|June 21, 2023
概括
肌痛性骨髓灰质炎 (MG) 中的单个自身抗体克隆可以通过多种机制攻击尼古丁性乙胆受体 (AChR). 这一发现揭示了自动反应克隆可以具有多方面的病原性能力,影响目前的MG疗法.
科学领域:
- 免疫学 免疫学 免疫学
- 神经科学是一个神经科学.
- 分子生物学分子生物学
背景情况:
- 自免疫性骨髓灰质炎 (MG) 涉及向尼古丁性乙胆受体 (AChR) 的血清自身抗体.
- 致病机制包括补充激活,受体阻塞和抗原调制.
- 个人自身抗体克隆对多致病性的贡献尚不清楚.
研究的目的:
- 调查单个自身抗体克隆是否可以调解MG的多种致病机制.
- 描述人类衍生ACHR特异性单克隆自身抗体 (mAbs) 的致病特征.
- 确定自身抗体特异性与致病能力之间的关联.
主要方法:
- 使用无偏见的B细胞培养查生成了11个人类ACHR特异性重组单克隆自身抗体 (mAbs) 的库.
- 通过专门的基于细胞的测定,评估了mAb的结合性质和致病特征.
- 利用表达单个 AChR 子单元 (α2βδε) 的新型 Jurkat 细胞系来确定 mAb 的特异性.
主要成果:
- 5个mAbs激活了补充,3个阻断了α-bungarotoxin的结合,7个诱导了抗原调制.
- 来自一个患者的两个与克隆相关的mAbs在多种致病机制中表现出高效率.
- 多病原性mAbs仅仅与ACHR的α子单元结合.
结论:
- 单个自反应性B细胞克隆可以有效地调解MG中多种模式的ACHR向病理.
- 致病机制在单克隆水平上并不相互排斥.
- 目前针对单一机制的MG疗法可能会被具有多方面的能力的自身抗体所规避.
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