A Novel Serum tsRNA for Diagnosis and Prediction of Nephritis in SLE.

A Novel Serum tsRNA for Diagnosis and Prediction of Nephritis in SLE.
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用于诊断和预测 SLE 肾炎的新型血清 tsRNA。

DOI:
10.3389/fimmu.2021.735105
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发表时间:
2021
影响因子:
7.3
通讯作者:
Wang Y
Wang Y
中科院分区:
医学2区
文献类型:
--
作者:
Yang P;Zhang X;Chen S;Tao Y;Ning M;Zhu Y;Liang J;Kong W;Shi B;Li Z;Shen H;Wang Y

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在各种疾病中都发现了人血清中转移RNA(TRNA)衍生的小非编码RNA(TsRNA)特征的失调。在这里,我们确定血清中tsRNAs的特征是否可以作为系统性红斑狼疮(SLE)诊断或预后的生物标志物。首先,对从SLE患者获得的血清tsRNAs进行小RNA测序,然后用TaqMan探针定量逆转录-聚合酶链式反应(RT-PCR)进行验证。采用受试者工作特征(ROC)曲线分析评价诊断效果。通过基因本体论(GO)和京都基因与基因组百科全书(KEGG)鉴定tsRNAs的生物学功能。我们首先分析了SLE血清中的tsRNA特征,发现TRF-His-GTG-1在SLE血清中显著上调。联合检测TRF-His-GTG-1和抗dsDNA可作为诊断SLE的生物标志物,其曲线下面积(AUC)为0.95(95%CI=0.92~0.99),敏感性(83.72%),特异性(94.19%)。无创性血清TRF-His-GTG-1还可用于SLE伴LN和非LN的鉴别诊断,AUC为0.81(95%CI,0.73~0.88),表现为敏感性为66.27%,特异性为96.15%。此外,血清tsRNA主要通过外切体分泌,可以直接靶向在调节免疫系统中发挥关键作用的信号分子。在本研究中,首次证明血清tsRNAs可作为非侵入性生物标志物用于SLE肾炎的有效诊断和预测。
Dysregulation of transfer RNA (tRNA)-derived small noncoding RNA (tsRNA) signatures in human serum has been found in various diseases. Here, we determine whether the signatures of tsRNAs in serum can serve as biomarkers for diagnosis or prognosis of systemic lupus erythematosus (SLE). Initially, small RNA sequencing was employed for the screening serum tsRNAs obtained from SLE patients, followed by validation with TaqMan probe-based quantitative reverse transcription-PCR (RT-PCR) assay. Receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic efficacy. The biological functions of tsRNAs were identified by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) assay. We first analyzed tsRNA signatures in SLE serum and identified that tRF-His-GTG-1 was significantly upregulated in SLE serum. The combination of tRF-His-GTG-1 and anti-dsDNA could serve as biomarkers for diagnosing SLE with a high area under the curve (AUC) of 0.95 (95% CI = 0.92–0.99), sensitivity (83.72%), and specificity (94.19%). Importantly, the noninvasive serum tRF-His-GTG-1 could also be used to distinguish SLE with LN or SLE without LN with AUC of 0.81 (95% CI, 0.73–0.88) and performance (sensitivity 66.27%, specificity 96.15%). Moreover, the serum tsRNA is mainly secreted via exosome and can directly target signaling molecules that play crucial roles in regulating the immune system. In this study, it has been demonstrated for the first time that serum tsRNAs can be employed as noninvasive biomarkers for the efficient diagnosis and prediction of nephritis in SLE.
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