在初级Sjögren综合征中,B细胞的多模式单细胞测序
Gustav Arvidsson1, Paulo Czarnewski2, Alina Johansson1
1Uppsala University, Uppsala, Sweden.
Arthritis & rheumatology (Hoboken, N.J.)
|August 23, 2023
概括
主要Sjögren综合征 (pSS) 患者具有Sjögren综合征抗原A/B (SSA/SSB) 自体抗体显示出不同的B细胞简介. 这些B细胞差异影响了pSS的疾病表现和结果.
科学领域:
- 免疫学 免疫学 免疫学
- 基因组学就是基因组学.
- 自免疫性疾病 自免疫性疾病
背景情况:
- B细胞在原发性Sjögren综合征 (pSS) 的发病过程中起着至关重要的作用.
- 患有Sjögren综合征抗原A/B (SSA/SSB) 自体抗体的患者往往会经历更严重的全身性疾病和不良结果.
- 了解pSS中的B细胞异质性对于患者分层和治疗至关重要.
研究的目的:
- 为了研究B细胞组成,基因表达和B细胞受体使用在由SSA/SSB抗体状态分层的pSS亚组中的B细胞组成,基因表达和B细胞受体使用的作用.
- 识别与pSS.中的疾病表现和抗体状态相关的B细胞中的分子差异.
主要方法:
- 单细胞RNA测序 (scRNA-seq) 和单细胞变异性,多样性和结合性 (VDJ) 基因测序 (scVDJ-seq) 在超过23万个pSS患者和健康对照者的B细胞上进行.
- 从患有pSS (SSA-,SSA+和SSA/SSB+亚组) 的患者和健康对照的外周血液中分离出B细胞.
- 无监督分析结合scRNA-seq和scVDJ-seq数据进行患者分层.
主要成果:
- 在SSA/SSB+ pSS患者中,原始和记忆B细胞的比例发生变化,干扰素诱导的基因表达增加.
- 与对照组相比,pSS子组中观察到IGHV基因 (IGHV1-69,IGHV4-30-4) 的使用差异.
- 在SSA/SSB+患者的B型记忆细胞中,未变异的VDJ转录的频率更高,表明体质突变受损.
结论:
- 这项研究揭示了pSS患者B细胞内显著的异质性和独特的分子特征.
- 这些发现提供了对影响pSS表型和结果的内在B细胞差异的见解.
- 综合分析使得基于B细胞概况的pSS中患者分层有所改善.
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