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鉴定银屑病和银屑病关节炎患者的循环 microRNA 图谱。

Identification of circulating microRNA patterns in patients in psoriasis and psoriatic arthritis.

机构信息

Ludwig Boltzmann Institute of Osteology, I Medical Department at Hanusch Hospital of OEGK, Vienna, Austria.

Karl Landsteiner Institute for Gastroenterology and Rheumatology, Rheuma-Zentrum Wien-Oberlaa, Vienna, Austria.

出版信息

Rheumatology (Oxford). 2023 Oct 3;62(10):3448-3458. doi: 10.1093/rheumatology/kead059.

Abstract

OBJECTIVE

miRNAs are small non-coding RNAs that control gene expression. Specific intra- and extracellular miRNA signatures have been identified in various diseases. Whether certain miRNA signatures are associated with psoriasis (PsO) and PsA is currently unknown. We aimed to search for circulating miRNA signatures associated with PsO and PsA patients.

METHODS

Expression of miRNAs was analysed by reverse transcription quantitative real-time PCR (RT-qPCR) in the serum of PsA, PsO patients and healthy controls. Demographic and disease-specific characteristics and imaging data from hand MRI were recorded. In the discovery phase, 192 miRNA assays were analysed in 48 samples (PsA, PsO, controls: each N = 16). For validation, 17 selected miRNAs were measured in the total population.

RESULTS

A total of 141 patients and controls were analysed (51 PsA, 40 PsO, 50 controls). In the discovery phase 51 miRNAs in PsO and 64 miRNAs in PsA were down- or upregulated compared with controls, with 33 miRNAs being changed in both (adj. P < 0.05). The 17 top candidates from discovery were assessed in the validation phase, 9 of them discriminated PsA and PsO from controls [area under the curve (AUC) ≥0.70, all P < 0.05]. Four miRNAs (miR-19b-3p, miR-21-5p, miR-92a-3p and let-7b-5p) were significantly differently regulated between PsO and PsA. A combination of these miRNAs increased the AUC to 0.92 in multivariate regression model to discriminate PsO and PsA.

CONCLUSION

miRNA signatures in PsA and PsO patients differ from controls. Nine miRNAs were differentially regulated in PsA and PsO patients, five of them previously reported to be involved in bone and cartilage metabolism, indicating an intimate association of psoriatic inflammation and bone/cartilage changes.

摘要

目的

miRNAs 是一种小的非编码 RNA,可以控制基因表达。已经在各种疾病中鉴定出特定的细胞内和细胞外 miRNA 特征。目前尚不清楚某些 miRNA 特征是否与银屑病(PsO)和银屑病关节炎(PsA)相关。我们旨在寻找与 PsO 和 PsA 患者相关的循环 miRNA 特征。

方法

通过逆转录定量实时 PCR(RT-qPCR)分析血清中的 miRNA 表达,对 PsA、PsO 患者和健康对照者进行分析。记录人口统计学和疾病特异性特征以及手部 MRI 的成像数据。在发现阶段,在 48 个样本(PsA、PsO、对照组:各 N=16)中分析了 192 个 miRNA 检测。在总人群中验证时,测量了 17 个选定的 miRNA。

结果

总共分析了 141 例患者和对照者(51 例 PsA、40 例 PsO、50 例对照者)。在发现阶段,与对照组相比,PsO 中有 51 个 miRNA 下调,PsA 中有 64 个 miRNA 下调,其中 33 个 miRNA 在两者中都发生了变化(调整 P<0.05)。从发现阶段中选择的 17 个最佳候选者在验证阶段进行了评估,其中 9 个能够区分 PsA 和 PsO 与对照组(曲线下面积(AUC)≥0.70,均 P<0.05)。在 PsO 和 PsA 患者之间,有 4 个 miRNA(miR-19b-3p、miR-21-5p、miR-92a-3p 和 let-7b-5p)的调节存在显著差异。这些 miRNA 的组合在多元回归模型中可将 AUC 提高到 0.92,以区分 PsO 和 PsA。

结论

PsA 和 PsO 患者的 miRNA 特征与对照组不同。在 PsA 和 PsO 患者中,有 9 个 miRNA 调节差异,其中 5 个以前报道与骨和软骨代谢有关,表明银屑病炎症与骨/软骨变化密切相关。

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