在血清阳性个体中,纵向外围血液多原子分析识别了免疫内型和预测模型,用于未来的类风湿性关节炎转化
medRxiv : the preprint server for health sciences
|February 27, 2026
概括
患有抗循环素蛋白 (anti-CCP) 抗体而患有类风湿性关节炎 (RA) 的个体在症状出现之前表现出明显的免疫细胞变化. 这些免疫特征可以预测风险人群的RA发展.
科学领域:
- 免疫学 免疫学 免疫学
- 类风湿病学 类风湿病学
- 基因组学就是基因组学.
背景情况:
- 抗循环氨酸蛋白 (anti-CCP) 抗体升高表明类风湿性关节炎 (RA) 风险,但从RA前到临床RA的过渡尚未完全理解.
- 确定驱动RA发展的免疫因素对于早期干预至关重要.
研究的目的:
- 在具有抗CCP抗体的个体中,研究临床类风湿性关节炎 (RA) 发生之前的免疫因素和细胞变化.
- 确定预测RA发展和分层风险的潜在生物标志物.
主要方法:
- 多模态单细胞分析 (转录组,表面蛋白质,T/B细胞受体测序,染色体可访问性) 在来自抗CCP抗体阳性个体的样本上进行.
- 分析包括在临床试验中患有RA (转化者) 和没有 (非转化者) 的个人.
主要成果:
- 转换器表现出外围辅助T (Tph) 细胞和特定的CD8+T细胞子集 (表达GZMK,GZMB) 的扩张,以及潜在的自反应T细胞受体.
- 转换器中的B细胞在RA发作之前显示了与年龄相关的B细胞特征的早期诱导.
- 表观遗传学分析显示,随着时间的推移,转化器中髓状细胞和NK细胞的染色质可访问性发生了明显的变化.
- 结合免疫和临床特征的预测模型准确地分层RA风险和预测疾病发病.
结论:
- 特定的免疫内型,包括Tph细胞和某些CD8+T细胞子集,与抗CCP抗体阳性个体的RA发展有关.
- 这些发现突出了预防策略和在RA前风险分层的潜在目标.
- 免疫分析可以预测风险人群中RA发病的可能性和时间.
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