Abstract
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.
Highlights
Systemic lupus erythematosus (SLE) is a heterogeneous inflammatory chronic autoimmune disorder characterized by progressive involvement of multiple-organ systems with alternating clinical exacerbations and remissions [1]
A total of 21 individuals were enrolled in this study: four patients withLN-IV, ten patients with SLE without nephritis (LNN group) and seven individuals without autoimmune disease (Controls) (Table 1)
We found 24 miRNAs differentially expressed when we compared the Lupus nephritis (LN)-IV group with the individuals of the control group, 16 miRNAs were found overexpressed and 8 miRNAs showed reduced levels between these two groups. 8 of these miRNAs have been previously associated with the regulation of SLE
Summary
Systemic lupus erythematosus (SLE) is a heterogeneous inflammatory chronic autoimmune disorder characterized by progressive involvement of multiple-organ systems with alternating clinical exacerbations and remissions [1]. Lupus nephritis (LN) is a common and debilitating feature of SLE. The precise immune mechanisms that drive the progression from benign autoimmunity to LN are largely unknown [3]. The diversity of clinical, serological and immunological symptoms are the result of the activation of varied immune components by complex molecular mechanisms that finely tuned the general process of protein production through DNA transcription and RNA translation; among these, circulating microRNAs play an important role. The role of miRNAs in the pathophysiology of lupus nephritis are far from being fully understood [2,4,5]
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