人类乙胆受体主要免疫原体区域的模仿物的开发,用于治疗神经硬化症
Vu B Trinh1,2, Robert H Fairclough1,2,3
1Department of Neurology, Davis School of Medicine, University of California, 1515 Newton Court, Davis, CA 95618, USA.
研究人员创建了乙胆受体 (AChR) 的仿真体,以研究肌痛性硬化症 (MG). 这些模仿者通过准抗AChR自身抗体来诊断和治疗MG有希望.
科学领域:
- 神经科学是一个神经科学.
- 免疫学 免疫学 免疫学
- 生物化学 生物化学
背景情况:
- 骨髓灰质炎 (MG) 是一种自身免疫性疾病,其特征是针对乙胆受体 (AChRs) 的自身抗体.
- AChR的主要免疫原性区域 (MIR) 是这些自身抗体的关键标,在人类MG和实验性自身免疫性肌痛性肌痛症 (EAMG) 中占自身免疫反应的50-70%.
- 了解ACHR MIRs自身抗体识别的结构基础对于开发诊断和治疗策略至关重要.
研究的目的:
- 设计和生产的模仿鱼雷和人类ACHRMIRs.
- 为了研究单克隆抗体 (mAbs) 和自身抗体 (Abs) 与这些模拟物的结合.
- 开发潜在的诊断工具和针对MG的抗原特异性治疗方法,基于这些仿真体.
主要方法:
- 合成39种氨基酸模仿鱼和人类ACHRMIRs的合成.
- 对MIR段的共价连接,以创建对形状敏感的结构.
- 测试来自EAMG大鼠和人类MG患者的抗MIRmAbs和血清与模拟物的结合.
- 局部导向的突变发生,以替代氨基酸并产生化学.
主要成果:
- 鱼和人类ACHRMIR的体模仿成功设计和生产.
- 具有共价连接的MIR段结合了大量的抗AChRmAbs.
- 结合人类和鱼氨基酸的化学显示了与抗MIR抗体的差异性结合.
- 特定的替代物削弱或维持了mAb的识别,为抗体结合表位提供了洞察力.
结论:
- 工程化模仿 AChR MIRs 可以有效地结合抗MIR自身抗体和单克隆抗体.
- 化学构造显示出开发诊断试验的潜力,以量化MG中的抗MIR抗体标位.
- 这些可以作为MG新型非类固醇抗原特异性治疗的基础,向自身抗体产生B细胞或促进自身抗体的去除.
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