Urinary exosome tsRNAs as novel markers for diagnosis and prediction of lupus nephritis

作者：Shanshan Chen, Xiaoshan Zhang, Kaifang Meng, Yifan Sun, Ruilu Shu, Yan Han, Qingxiu Feng, Zhiyang Li, Ping Yang, Jun Liang · 发表于：Frontiers in Immunology · 年份：2023 · DOI：10.3389/fimmu.2023.1077645 · 被引用次数：60 · 研究领域：Systemic Lupus Erythematosus Research、Extracellular vesicles in disease、RNA regulation and disease

Objective Lupus nephritis (LN) is one of the most severe organ manifestations of systemic lupus erythematosus (SLE). Early identification of renal disease in SLE is important. Renal biopsy is currently recognized as the gold standard for diagnosing LN, however, it is invasive and inconvenient for dynamic monitoring. Urine has been considered more promising and valuable than blood in identifying inflamed kidney tissue. Here, we determine whether the signatures of tRNA-derived small noncoding RNA (tsRNA) in urinary exosomes can serve as novel biomarkers for the diagnosis of LN. Methods tsRNA sequencing was performed in exosome extracted from pooled urine of 20 LN patients and 20 SLE without LN, and the top 10 upregulated tsRNAs were screened as candidate markers of LN. The candidate urinary exosomal tsRNAs were primarily elected by TaqMan probe-based quantitative reverse transcription-PCR (RT-PCR) in 40 samples (20 LN and 20 SLE without LN) in the training phase. In the validation phase, selected tsRNAs from the training phase were further confirmed in a larger cohort (54 LN patients and 39 SLE without LN). Receiver operating characteristic curve (ROC) analysis was conducted to evaluate the diagnostic efficacy. Results Upregulated levels of tRF3-Ile-AAT-1 and tiRNA5-Lys-CTT-1 in the urinary exosomes were observed in LN compared with SLE without LN ( P < 0.0001 and P < 0.001) and healthy controls ( P < 0.01 and P < 0.01), with the area under the curve...