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单细胞细胞表面是风湿性关节炎中自抗原生成的独特地点

Mekha A Thomas¹, Pooja Naik¹, Hong Wang¹

¹Division of Rheumatology, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD 21224.

Proceedings of the National Academy of Sciences of the United States of America

|April 17, 2024

概括

单细胞在其表面表达活跃的达尔基宁脱胺酶IV (PAD4),在表面表达纤维原和Mac-1等素蛋白质. 这种表面化会产生由抗化蛋白自身抗体 (ACPAs) 在类风湿性关节炎 (RA) 中识别的自身抗原.

科学领域:

免疫学免疫学免疫学
类风湿病学类风湿病学
细胞生物学细胞生物学

背景情况:

反素蛋白自身抗体 (ACPA) 是类风湿性关节炎 (RA) 的关键生物标志物.
细胞起源和引发RA自身免疫的素化驱动机制尚未完全理解.
达尔吉林脱胺酶IV (PAD4) 参与RA素化,但其单细胞特异性作用尚未得到充分研究.

研究的目的:

为了研究单细胞衍生PAD4.4的亚细胞局部化和酶活性.
为了识别由单细胞PAD4.4产生的细胞外和细胞表面自身抗原.
确定单细胞表面PAD4在类风湿性关节炎病原体中的作用.

主要方法:

单细胞培养和表征.
评估PAD4在细胞表面和细胞外蛋白的酶活性.
质谱测量用于鉴定素基质.
针对ACPA反应性的ELISA和患者血清分析.

主要成果:

单细胞在其细胞表面表达活跃的PAD4,能够在细胞外纤维素和内源性表面蛋白中产生素.
表面 PAD4 林化纤维素和 Mac-1 整合素子单元 (CD11b/CD18).
在25%的RA患者中,Citrullinated Mac-1被ACPAs识别,并与疾病严重程度标志物相关联.

结论:

单细胞细胞表面是产生RA中素自抗原的重要部位.
单细胞表面的PAD4活性有助于RA素瘤,向Mac-1等蛋白质.
这些发现突出了RA自身免疫的新型机制,涉及单细胞衍生的细胞外和细胞表面素化.

关键词:

这是自抗体的自抗体.素化是指素化.单细胞 (Monocytes) 是一种单细胞.丁氨酸脱酶是什么?类风湿性关节炎类风湿性关节炎

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