在类风湿性宫外生殖中心对流体衍生的自身抗原的自身免疫会加剧关节炎,并影响临床反应
Elisa Corsiero1, Mattia Caliste1, Lucas Jagemann1
1Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London (QMUL), London, United Kingdom.
The Journal of clinical investigation
|July 1, 2024
概括
类风湿性关节炎的B细胞会产生针对HSP60.0.等自身抗原的自身抗体. 这些抗体促进炎症,并与疾病亚型相关,可能预测类风湿性关节炎 (RA) 治疗反应.
科学领域:
- 免疫学 免疫学 免疫学
- 类风湿病学 类风湿病学
- 分子生物学分子生物学
背景情况:
- 在类风湿性关节炎 (RA) 关节中的异位淋巴体结构 (ELS) 驱动对局部自身抗原的自身免疫力.
- 来自突性B细胞的风湿性关节炎复合单克隆抗体 (RA-rmAbs) 识别纤维细胞样突细胞 (FLS).
研究的目的:
- 为了确定FLS衍生的自抗原,在RA中推动自身免疫.
- 确定抗FLS抗体在慢性炎症中的作用.
主要方法:
- 针对FLS提取物的RA-rmAbs特异性的表征.
- 在原诱导关节炎小鼠模型中评估病原性质.
- 在患者的突液中检测抗HSP60抗体.
- 使用大量RNA-Seq和GeoMx-DSP.HSPD1和CALR基因表达的分析.
- 与ELS和B细胞枯竭疗法 (rituximab) 相关的HSP60表达的评估.
主要成果:
- 一个RA-rmAbs的子集识别了HSP60,对calreticulin/vimentin有一些交叉反应.
- 抗FLSRA-rmAbs在小鼠模型中表现出致病性.
- 反HSP60抗体在RA和骨关节炎 (OA) 中更为普遍.
- 同胞性HSP60和CALR基因表达与RA病型和ELS相关.
- 利图西马布治疗减少了突性HSP60表达,与治疗反应相关.
结论:
- 在RA中,共结体 stromal 自身抗原,特别是 HSP60 是致病性自身抗体的目标.
- 这些自身抗原与特定的RA病变型相关.
- 协性HSP60可以作为患者分层的生物标志物,并预测对B细胞枯竭疗法的反应.
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