【科技前瞻】EBioMedicine：外泌体可作为诊断特发性肾病综合征的生物标志物

生物_医药_科研 2019-01-16

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小儿特发性肾病综合征（nephrotic syndrome，NS）是一种常见于儿童的慢性肾小球疾病，主要归因于免疫介导的炎症性疾病和基因突变。NS伴随严重的并发症，包括细菌感染、血栓栓塞和脂质异常。由于其症状和并发症具有多样性，因此缺乏患者预后的准确预测因子。肾组织活检是判断其病理类型和进展的标准方法，但这是一种具有潜在风险的侵入性方法，通常不适用于连续监测。因此，开发NS非侵入性诊断和预后生物标志物及方法十分迫切。

有研究指出，外泌体miRNA可作为肾脏疾病理想的非侵入性生物标志物，此前其在小儿肾病综合征的诊断上研究较少。近日，来自南方医科大学南京临床医学院、南京大学生命科学学院的研究人员探讨了尿液外泌体miRNA对小儿特发性肾病综合征的临床价值。该团队此前研究发现了一组在肾病患儿肾组织中水平失调的miRNA，并与肾病的发病机制有关。这些miRNA在NS患儿的血清或尿液中也显著增加，并且随着患者的临床缓解而显著降低。在这项新的研究中，研究人员从129名NS儿童和126名年龄与性别匹配的健康对照组中收集尿液样本，通过高通量Illumina测序合成技术分析尿液外泌体的miRNA谱，然后通过RT-qPCR对两个分组中的表达进行验证。结果发现，与对照组相比，Illumina SBS在NS儿童中鉴定出30个显著增加的尿外泌体miRNA（≥5倍，P<0.05）。选择15个mirna用于进一步研究，其中5个（mir-194-5p，mir-146b-5p，mir-378a-3p，mir-23b-3p，mir-30a-5p）通过rt-qpcr验证其在ns中稳定增加（>3倍，P<><>

此前研究报道显示，多种肾脏疾病，如IgA肾病、狼疮性肾炎和慢性肾病成人患者尿液中某些外泌体miRNA的表达水平发生了显著变化，提示尿液外泌体miRNA可能具有作为成人肾脏疾病活动的生物标志物。这项研究找到了小儿特发性NS患者的总体尿液外泌体miRNA特征，为开发小儿NS诊断和检测液体活检工具提供了重要依据。

推荐阅读原文：
Increased urinary exosomal microRNAs in children with idiopathic nephrotic syndrome.
BACKGROUND:
Urinary exosomal miRNAs are gaining increasing attention for their potential as ideal non-invasive biomarkers for kidney diseases; however, little is known about their diagnostic ability for paediatric nephrotic syndrome (NS). This study explored the clinical value of urinary exosomal miRNAs for paediatric idiopathic NS.
METHODS:
Urine samples were collected from 129 NS children and 126 age-/sex-matched healthy controls. The miRNA profile of urinary exosomes was analysed by high-throughput Illumina sequencing via synthesis (SBS) technology followed by verification with a quantitative reverse-transcription polymerase chain reaction (RT-qPCR) assay arranged in two independent cohorts. Additionally, paired urine samples from 65 of these patients were collected before and after treatment.
FINDINGS:
The Illumina SBS identified 30 markedly increased urinary exosomal miRNAs in NS children compared with controls (≥ 5-fold, P <0 .05). fifteen="" mirnas="" were="" selected="" for="" further="" investigation,="" of="" which="" 5="" (mir-194-5p,="" mir-146b-5p,="" mir-378a-3p,="" mir-23b-3p="" and="" mir-30a-5p)="" were="" verified="" by="" rt-qpcr="" to="" be="" significantly="" and="" steadily="" increased="" in="" ns="" (=""> 3-fold, P < 0.01) and="" markedly="" reduced="" during="" the="" clinical="" remission="" period="">< 0.001). moreover,="" the="" concentrations="" of="" mir-194-5p="" and="" mir-23b-3p="" were="" significantly="" positively="" correlated="" with="" the="" urine="" protein="" content="" and="" were="" markedly="" higher="" in="" the="" high="" urine="" protein="" group="" than="" in="" the="" low="" urine="" protein="" group="">< 0.001 and="">< 0.01,>
INTERPRETATIONS:
We identified 5 altered urinary exosomal miRNAs in NS children with disease progression and treatment. These urinary exosomal miRNAs could be promising and non-invasive potential biomarker candidates for diagnosing, monitoring and stratifying paediatric NS.