在肌肉炎中病理性自身抗体内部化
Iago Pinal-Fernandez1,2, Sandra Muñoz-Braceras3, Maria Casal-Dominguez3,2
1Muscle Disease Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA andrew.mammen@nih.gov iago.pinalfernandez@nih.gov.
在肌肉炎中,自身抗体进入肌肉细胞并破坏其功能,挑战了以前的假设. 这一发现对了解自身免疫性肌肉病变和开发向治疗有意义.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 肌肉生物学 肌肉生物学
背景情况:
- 针对细胞内蛋白的自身抗体在自身免疫性疾病中很普遍.
- 这些自身抗体在肌肉炎中的作用一直受到争议,因为人们认为它们无法透到肌肉细胞.
研究的目的:
- 为了调查自身抗体是否可以进入肌肉炎的活体肌肉细胞.
- 为了确定内部化自身抗体是否会导致肌肉细胞的功能变化.
主要方法:
- 同焦点免疫光显微镜用于定位肌肉活检中的抗体.
- 669个肌肉样本 (肌肉炎,对照) 的散装RNA测序.
- 患者抗体被电穿透到培养的肌细胞中,然后进行RNA测序.
主要成果:
- 在肌肉纤维中发现了肌肉炎自身抗体,与其自身抗原共定位.
- 用针对转录调节者的自身抗体进行的肌肉活检显示了转录学变化,表明了自身抗原功能障碍.
- 具体的例子包括患有抗PM/Scl抗体的患者的改变RNA处理.
- 在体外实验证实,患者的抗体会在肌肉细胞中诱导类似的转录基因变化.
结论:
- 在肌肉炎中,自身抗体被内化到活体肌肉细胞中.
- 内化自身抗体会破坏其目标自身抗原的功能,导致可观察到的生物效应.
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