Navarro-Quiroz Elkin, Pacheco-Lugo Lisandro, Navarro-Quiroz Roberto, Lorenzi Hernan, España-Puccini Pierine, Díaz-Olmos Yirys, Almendrales Lisneth, Olave Valeria, Gonzalez-Torres Henry, Diaz-Perez Anderson, Dominguez Alex, Iglesias Antonio, García Raul, Aroca-Martinez Gustavo
Grupo de Nefrología, Universidad Simón Bolívar, Barranquilla,Colombia.
Centro de Investigación en Salud para el Trópico, Universidad Cooperativa de Colombia, Santa Marta, Colombia.
PLoS One. 2017 Nov 14;12(11):e0187973. doi: 10.1371/journal.pone.0187973. eCollection 2017.
Renal involvement in Systemic Lupus Erythematous (SLE) patients is one of the leading causes of morbidity and a significant contributor to mortality. It's estimated that nearly 50% of SLE individuals develop kidney disease in the first year of the diagnosis. Class IV lupus nephritis (LN-IV) is the class of lupus nephritis most common in Colombian patients with SLE. Altered miRNAs expression levels have been reported in human autoimmune diseases including lupus. Variations in the expression pattern of peripheral blood circulating miRNAs specific for this class of lupus nephritis could be correlated with the pathophysiological status of this group of individuals. The aim of this study was to evaluate the relative abundance of circulating microRNAs in peripheral blood from Colombian patients with LN-IV. Circulating miRNAs in plasma of patients with diagnosis of LN-IV were compared with individuals without renal involvement (LNN group) and healthy individuals (CTL group). Total RNA was extracted from 10 ml of venous blood and subsequently sequenced using Illumina. The sequences were processed and these were analyzed using miRBase and Ensembl databases. Differential gene expression analysis was carried out with edgeR and functional analysis were done with DIANA-miRPath. Analysis was carried out using as variables of selection fold change (≥2 o ≤-2) and false discovery rate (0.05). We identified 24 circulating microRNAs with differential abundance between LN-IV and CTL groups, fourteen of these microRNAs are described for the first time to lupus nephritis (hsa-miR-589-3p, hsa-miR-1260b, hsa-miR-4511, hsa-miR-485-5p, hsa-miR-584-5p, hsa-miR-543, hsa-miR-153-3p, hsa-miR-6087, hsa-miR-3942-5p, hsa-miR-7977, hsa-miR-323b-3p, hsa-miR-4732-3p and hsa-miR-6741-3p). These changes in the abundance of miRNAs could be interpreted as alterations in the miRNAs-mRNA regulatory network in the pathogenesis of LN, preceding the clinical onset of the disease. The findings thus contribute to understanding the disease process and are likely to pave the way towards identifying disease biomarkers for early diagnosis of LN.
系统性红斑狼疮（SLE）患者的肾脏受累是发病的主要原因之一，也是死亡率的重要促成因素。据估计，近50%的SLE患者在诊断后的第一年内会发展为肾脏疾病。IV型狼疮性肾炎（LN-IV）是哥伦比亚SLE患者中最常见的狼疮性肾炎类型。在包括狼疮在内的人类自身免疫性疾病中，已有miRNA表达水平改变的报道。这类狼疮性肾炎外周血循环miRNA表达模式的变化可能与该组个体的病理生理状态相关。本研究的目的是评估哥伦比亚LN-IV患者外周血中循环miRNA的相对丰度。将诊断为LN-IV的患者血浆中的循环miRNA与无肾脏受累的个体（LNN组）和健康个体（CTL组）进行比较。从10毫升静脉血中提取总RNA，随后使用Illumina进行测序。对序列进行处理，并使用miRBase和Ensembl数据库进行分析。使用edgeR进行差异基因表达分析，使用DIANA-miRPath进行功能分析。分析以倍数变化（≥2或≤-2）和错误发现率（0.05）作为选择变量。我们在LN-IV组和CTL组之间鉴定出24种循环miRNA丰度存在差异，其中14种miRNA首次被描述与狼疮性肾炎相关（hsa-miR-589-3p、hsa-miR-1260b、hsa-miR-4511、hsa-miR-485-5p、hsa-miR-584-5p、hsa-miR-543、hsa-miR-153-3p、hsa-miR-6087、hsa-miR-39,42-5p、hsa-miR-7977、hsa-miR-323b-3p、hsa-miR-4732-3p和hsa-miR-6741-3p）。这些miRNA丰度的变化可解释为在LN发病机制中miRNA-mRNA调控网络发生改变，早于疾病的临床发作。因此，这些发现有助于理解疾病过程，并可能为识别LN早期诊断的疾病生物标志物铺平道路。
