Multi-omics monitoring of drug response in rheumatoid arthritis in pursuit of molecular remission.
Multi-omics monitoring of drug response in rheumatoid arthritis in pursuit of molecular remission.
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DOI：
10.1038/s41467-018-05044-4
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发表时间：
2018-07-16
影响因子：
16.6
通讯作者：
Takeuchi T
中科院分区：
文献类型：
--
作者：
Tasaki S;Suzuki K;Kassai Y;Takeshita M;Murota A;Kondo Y;Ando T;Nakayama Y;Okuzono Y;Takiguchi M;Kurisu R;Miyazaki T;Yoshimoto K;Yasuoka H;Yamaoka K;Morita R;Yoshimura A;Toyoshiba H;Takeuchi T
在没有药物治疗的情况下，类风湿关节炎(RA)患者的持续临床缓解(CR)尚未实现。这意味着CR和健康状态之间有实质性的差异，但它还没有被量化。我们报告了对RA患者外周血中多组学水平药物反应的纵向监测。我们的数据显示，药物治疗在转录组、血清蛋白质组和免疫表型水平上改变了与HCS更接近的分子图谱。患者随访表明，药物治疗后的分子图谱与长期稳定的CR有关。此外，我们还确定了对药物治疗具有抗药性的分子签名。这些信号与RA相关，与已知的疾病严重程度指数无关，主要由中性粒细胞、单核细胞和淋巴细胞的失衡来解释。这种高维表型提供了分子缓解的定量测量，并说明了理解药物反应的多组学方法。关于类风湿性关节炎(RA)治疗后分子变化的信息很少。在这里，作者报道了一项多组学研究，收集了患者的转录组、蛋白质组和免疫表型数据，以帮助了解药物治疗对RA分子表型的影响。
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. Little information is available on molecular changes in response to treatment of rheumatoid arthritis (RA). Here the authors report a multi-omics study collecting patients' transcriptome, proteome, and immunophenotype data to help understand the impact of drug treatments on RA molecular phenotypes.
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通讯作者：
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