Immune cells gene expression from rheumatoid arthritis and healthy donors. Homo sapiens

Sustained clinical remission (CR) without drug treatment has not been achieved in patients with rheumatoid arthritis (RA). This implies a substantial difference between CR and the healthy state, but it has yet to be quantified. We report a longitudinal monitoring of the drug response at multi-omics levels in the peripheral blood of patients with RA. Our data reveal that drug treatments alter the molecular profile closer to that of HCs at the transcriptome, serum proteome and immunophenotype level. Patient follow-up suggests that the molecular profile after drug treatments is associated with long-term stable CR. In addition, we identify molecular signatures that are resistant to drug treatments. These signatures are associated with RA independently of known disease severity indexes and are largely explained by the imbalance of neutrophils, monocytes, and lymphocytes. This high-dimensional phenotyping provides a quantitative measure of molecular remission and illustrates a multi-omics approach to understanding drug response. Overall design: Transcriptome of sorted immune cells from patients with RA and healthy volunteers.

类风湿关节炎（RA）患者尚未实现无需药物治疗的持续临床缓解（CR）。这提示临床缓解与健康状态间存在显著差异，但该差异尚未被量化。本研究对类风湿关节炎患者外周血的多组学水平药物应答情况进行了纵向监测。研究数据显示，药物治疗可使患者的分子特征在转录组、血清蛋白质组及免疫表型层面更趋近健康对照者（HCs）。患者随访结果表明，药物治疗后的分子特征与长期稳定的临床缓解相关。此外，本研究鉴定出了对药物治疗耐受的分子特征，此类特征与类风湿关节炎的关联独立于已知的疾病严重程度指数，且该关联在很大程度上可由中性粒细胞、单核细胞及淋巴细胞的失衡所解释。本高维表型分析提供了一种分子缓解的量化评估手段，并阐明了一种用于解析药物应答的多组学研究方法。整体实验设计：对类风湿关节炎患者与健康志愿者的分选免疫细胞进行转录组分析。