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银屑病关节炎临床缓解的分子谱分析揭示了 和 基因的失调:一项基因表达研究。

Molecular profiling of clinical remission in psoriatic arthritis reveals dysregulation of and genes: a gene expression study.

机构信息

Department of Medical Science and Public Health, University of Cagliari, Cagliari, Italy.

Rheumatology Unit, Azienda Ospedaliero - Universitaria di Cagliari, Cagliari, Italy.

出版信息

Front Immunol. 2023 Oct 27;14:1274539. doi: 10.3389/fimmu.2023.1274539. eCollection 2023.

Abstract

BACKGROUND

In psoriatic arthritis (PsA), the primary goal of treatment is clinical remission. This study aimed to characterize the molecular profile underlying the induced clinical remission in patients with PsA, comparing the remission state and the healthy condition.

METHODS

Whole blood transcriptomic analysis was performed on groups of 14 PsA patients in TNFi-induced clinical remission (DAPSA ≤ 4), 14 PsA patients with active disease (DAPSA > 14), and 14 healthy controls (HCs). Then, all differentially expressed genes (DEGs) derived from remission vs. HC comparison were analyzed for functional and biological characteristics by bioinformatics software. The gene expression of 12 genes was then validated by RT-qPCR in an extended cohort of 39 patients in clinical remission, 40 with active disease, and 40 HCs.

RESULTS

The transcriptomic analysis of PsA remission vs. HCs highlighted the presence of 125 DEGs, and out of these genes, 24 were coding genes and showed a great involvement in immune system processes and a functional network with significant interactions. The RT-qPCR validation confirming the down- and upregulation of (FC -2.0; 0.005) and (FC +1.5; 0.005) genes, respectively, in line with their role in orchestrating inflammation and bone metabolism processes, may be related to PsA pathophysiology.

CONCLUSION

The transcriptomic profile of clinical remission in PsA is similar to a healthy condition, but not identical, differing for the expression of and genes, which appears to play a key role in its achievement.

摘要

背景

在银屑病关节炎(PsA)中,治疗的主要目标是临床缓解。本研究旨在通过比较缓解状态和健康状态,描述 PsA 患者诱导临床缓解的分子特征。

方法

对 14 例接受 TNFi 诱导临床缓解(DAPSA≤4)的 PsA 患者、14 例活动期疾病(DAPSA>14)的 PsA 患者和 14 例健康对照者(HC)的全血转录组进行分析。然后,通过生物信息学软件对从缓解与 HC 比较中得出的所有差异表达基因(DEGs)进行功能和生物学特征分析。然后,通过 RT-qPCR 在扩展队列的 39 例临床缓解患者、40 例活动期疾病患者和 40 例 HC 中验证 12 个基因的表达。

结果

PsA 缓解与 HC 比较的转录组分析突出了 125 个 DEGs 的存在,其中 24 个是编码基因,它们在免疫系统过程中具有重要作用,并且具有显著相互作用的功能网络。RT-qPCR 验证证实了基因的下调(FC-2.0; 0.005)和基因的上调(FC+1.5; 0.005),与它们在协调炎症和骨代谢过程中的作用一致,可能与 PsA 发病机制有关。

结论

PsA 临床缓解的转录组谱与健康状况相似,但不完全相同,差异在于基因和基因的表达,它们似乎在实现缓解方面发挥关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc8e/10641465/57be816140a2/fimmu-14-1274539-g001.jpg

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