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

Ping Yang,Yijia Zhu,Xiaoshan Zhang,Han Shen,Shanshan Chen,Mingzhe Ning,Yanbo Wang,Wei Kong,Jun Liang,Yue Tao,Zhiyang Li,Bo Shi

doi:10.3389/fimmu.2021.735105

Abstract

ObjectiveDysregulation 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).MethodsInitially, 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.ResultsWe 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.ConclusionIn 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.

Highlights

Systemic lupus erythematosus (SLE) is a representative autoimmune disease leading to systemic autoimmunity resulting in various organ damage
The presence of stable tsRNAs in human serum has been confirmed by recent studies [26]
To identify the tsRNA profile in SLE patients, all participants were divided into three groups according to the clinical standard, including SLE without Lupus nephritis (LN), SLE with LN, and healthy control

Summary

Introduction

Systemic lupus erythematosus (SLE) is a representative autoimmune disease leading to systemic autoimmunity resulting in various organ damage. SLE mainly occurs in women of childbearing age characterized with volcanic autoantibodies [1,2,3,4]. Both genetic and environmental factors are considered to be involved, but the precise pathogenesis of SLE is still unclear. Lupus nephritis (LN) is one of the most severe organ manifestations of SLE and a kind of glomerulonephritis. LN hugely contributes to the severity of the SLE, as 10% of LN patients acquire end-stage renal disease (ESRD) [7]. It is urgent to explore new biomarkers to distinguish LN from SLE

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Results

Conclusion