Immunomics analysis of rheumatoid arthritis identified precursor dendritic cells as a key cell subset of treatment resistance.
Immunomics analysis of rheumatoid arthritis identified precursor dendritic cells as a key cell subset of treatment resistance.
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DOI：
10.1136/ard-2022-223645
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发表时间：
2023-06
影响因子：
27.4
通讯作者：
中科院分区：
文献类型：
--
作者：
类风湿性关节炎（RA）治疗反应可变的免疫学基础知之甚少。我们对外周血免疫细胞亚群进行了大规模的转录组分析，以鉴定预测治疗耐药性的免疫细胞。我们分离了55名需要添加新治疗的RA患者和39名健康对照的18个外周血免疫细胞亚群，并进行了RNA测序。RA的转录组变化和治疗效果进行了系统的表征。评估免疫细胞基因模块与治疗抗性之间的关联。我们使用定量PCR（qPCR）和质谱流式细胞术分析队列验证了已识别参数对治疗耐药性的预测价值。我们还通过滑膜单细胞RNA测序分析鉴定了该群体的特征。RA患者的免疫细胞的特征是干扰素和IL 6-JAK-STAT 3信号传导增强，治疗后表现出部分正常化。浆细胞样树突状细胞（pDC）的基因表达模块反映了树突状细胞前体（pre-DC）的扩增，与治疗抗性的相关性最强。I型干扰素信号传导与前DC基因表达呈负相关。独立队列中的qPCR和质谱分析证实，在治疗抵抗患者中，治疗前前DC相关基因表达和前DC比例显著较高。一群滑膜DC表现出前DC和促炎性常规DC 2的特征。外周血中前DC的增加预测RA治疗抵抗。前DC可能与RA治疗反应具有病理生理学相关性。
Little is known about the immunology underlying variable treatment response in rheumatoid arthritis (RA). We performed large-scale transcriptome analyses of peripheral blood immune cell subsets to identify immune cells that predict treatment resistance. We isolated 18 peripheral blood immune cell subsets of 55 patients with RA requiring addition of new treatment and 39 healthy controls, and performed RNA sequencing. Transcriptome changes in RA and treatment effects were systematically characterised. Association between immune cell gene modules and treatment resistance was evaluated. We validated predictive value of identified parameters for treatment resistance using quantitative PCR (qPCR) and mass cytometric analysis cohorts. We also characterised the identified population by synovial single cell RNA-sequencing analysis. Immune cells of patients with RA were characterised by enhanced interferon and IL6-JAK-STAT3 signalling that demonstrate partial normalisation after treatment. A gene expression module of plasmacytoid dendritic cells (pDC) reflecting the expansion of dendritic cell precursors (pre-DC) exhibited strongest association with treatment resistance. Type I interferon signalling was negatively correlated to pre-DC gene expression. qPCR and mass cytometric analysis in independent cohorts validated that the pre-DC associated gene expression and the proportion of pre-DC were significantly higher before treatment in treatment-resistant patients. A cluster of synovial DCs showed both features of pre-DC and pro-inflammatory conventional DC2s. An increase in pre-DC in peripheral blood predicted RA treatment resistance. Pre-DC could have pathophysiological relevance to RA treatment response.
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影响因子：
27.4
作者：
Figueiredo, Camille P.;Bang, Holger;Schett, Georg
通讯作者：
Schett, Georg
影响因子：
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通讯作者：
Louis-Plence, Pascale
影响因子：
16.6
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影响因子：
32.4
作者：
Dutertre, Charles-Antoine;Becht, Etienne;Ginhoux, Florent
通讯作者：
Ginhoux, Florent
影响因子：
64.8
作者：
Maier B;Leader AM;Chen ST;Tung N;Chang C;LeBerichel J;Chudnovskiy A;Maskey S;Walker L;Finnigan JP;Kirkling ME;Reizis B;Ghosh S;D'Amore NR;Bhardwaj N;Rothlin CV;Wolf A;Flores R;Marron T;Rahman AH;Kenigsberg E;Brown BD;Merad M
通讯作者：
Merad M