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类风湿关节炎患者 T 细胞水平的分子缓解。

Molecular remission at T cell level in patients with rheumatoid arthritis.

机构信息

Division of Rheumatology, Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.

Immunology Unit, Takeda Pharmaceutical Co Ltd, Fujisawa-Shi, ResearchKanagawa, Japan.

出版信息

Sci Rep. 2021 Aug 17;11(1):16691. doi: 10.1038/s41598-021-96300-z.

Abstract

While numerous disease-modifying anti-rheumatic drugs (DMARDs) have brought about a dramatic paradigm shift in the management of rheumatoid arthritis (RA), unmet needs remain, such as the small proportion of patients who achieve drug-free status. The aim of this study was to explore key molecules for remission at the T cell level, which are known to be deeply involved in RA pathogenesis, and investigate the disease course of patients who achieved molecular remission (MR). We enrolled a total of 46 patients with RA and 10 healthy controls (HCs). We performed gene expression profiling and selected remission signature genes in CD4 T cells and CD8 T cells from patients with RA using machine learning methods. In addition, we investigated the benefits of achieving MR on disease control. We identified 9 and 23 genes that were associated with clinical remission in CD4 and CD8 T cells, respectively. Principal component analysis (PCA) demonstrated that their expression profiling was similar to those in HCs. For the remission signature genes in CD4 T cells, the PCA result was reproduced using a validation cohort, indicating the robustness of these genes. A trend toward better disease control was observed during 12 months of follow-up in patients treated with tocilizumab in deep MR compared with those in non-deep MR, although the difference was not significant. The current study will promote our understanding of the molecular mechanisms necessary to achieve deep remission during the management of RA.

摘要

虽然许多疾病修饰抗风湿药物 (DMARDs) 已经在类风湿关节炎 (RA) 的治疗中带来了巨大的范式转变,但仍存在未满足的需求,例如达到无药物状态的患者比例较小。本研究旨在探讨 T 细胞水平缓解的关键分子,这些分子被认为与 RA 的发病机制密切相关,并研究达到分子缓解 (MR) 的患者的疾病过程。我们共纳入了 46 名 RA 患者和 10 名健康对照者 (HCs)。我们进行了基因表达谱分析,并使用机器学习方法从 RA 患者的 CD4 T 细胞和 CD8 T 细胞中选择缓解特征基因。此外,我们还研究了达到 MR 对疾病控制的益处。我们在 CD4 和 CD8 T 细胞中分别鉴定了 9 个和 23 个与临床缓解相关的基因。主成分分析 (PCA) 表明,它们的表达谱与 HCs 相似。对于 CD4 T 细胞中的缓解特征基因,使用验证队列重现了 PCA 结果,表明这些基因具有稳健性。在接受托珠单抗治疗的患者中,与非深度 MR 患者相比,在深度 MR 患者中,在 12 个月的随访期间观察到疾病控制的趋势更好,尽管差异不显著。本研究将促进我们对 RA 管理中达到深度缓解所需的分子机制的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e90a/8371080/dbeca12ad51b/41598_2021_96300_Fig1_HTML.jpg

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