Altered levels of immune-regulatory microRNAs in plasma samples of patients with lupus nephritis

Abstract

Introduction: Lupus nephritis (LN) is a major cause of mortality and morbidity in the patients with lupus, a chronic autoimmune disease. The role of genetic and epigenetic factors is emphasized in the pathogenesis of LN. The aim of the present study was to evaluate the levels of immune-regulatory microRNAs (e.g., miR-31, miR-125a, miR-142-3p, miR-146a, and miR-155) in plasma samples of patients with LN. Methods: In this study, 26 patients with LN and 26 healthy individuals were included. The plasma levels of the microRNAs were evaluated by a quantitative real-time PCR. Moreover, the correlation of circulating plasma microRNAs with disease activity and pathological findings along with their ability to distinguish patients with LN were assessed. Results: Plasma levels of miR-125a (P = 0.048), miR-146a (P = 0.005), and miR-155 (P< 0.001) were significantly higher in comparison between the cases and controls. The plasma level of miR-146a significantly correlated with the level of anti-double strand-DNA antibody and proteinuria. Moreover, there was a significant correlation between miR-142-3p levels and disease chronicity and activity index (P <0.05). The multivariate ROC curve analysis indicated the plasma circulating miR-125a, miR-142-3p, miR-146, and miR-155 together could discriminate most of the patients with LN from controls with area an under curve (AUC) of 0.89 [95% CI, 0.80-0.98, P<0.001], 88% sensitivity, and 78% specificity. Conclusion: Based on the findings of the present study, the studied microRNAs may be involved in the pathogenesis and development of LN and have the potential to be used as diagnostic and therapeutic markers in LN.

Diagnostic significance of circulating miRNAs in systemic lupus erythematosus

“…However, five articles were excluded by reading their complete articles due to article types, seven studies lacked available data to construct a 2×2 table, and four articles lacked a comparison between SLE patients and healthy controls. Finally, 17 studies [17][18][19][20][21][31][32][33][34][35][36][37][38][39][40][41][42] were included in the meta-analysis. The process of study selection was illustrated in Fig 1. Except the study of Zununi Vahed et al [42] is a cross-sectional trial, all others are prospective trials.…”

“…Finally, 17 studies [17][18][19][20][21][31][32][33][34][35][36][37][38][39][40][41][42] were included in the meta-analysis. The process of study selection was illustrated in Fig 1. Except the study of Zununi Vahed et al [42] is a cross-sectional trial, all others are prospective trials. Among them, 41 individual diagnostic tests were extracted for total mixed miRNA (TmiR) evaluation; five individual diagnostic tests were extracted for miR-21 evaluation, 36 individual diagnostic tests were enrolled for total mixed miRNA knock out miR-21 (TmiRs-KO-21) evaluation.…”

“…Additionally, the ideal time for specimen acquisition was before treatment. Unfortunately, only two of the studies [17,31] involved in our meta-analysis indicated that blood samples were collected before treatment, while six studies [20,33,37,39,40,42] did not clarify when the specimens were obtained, five studies [18,19,21,36,41] stated that samples were collected during the period of treatments, and four articles [32,34,35,38] indicated that the time for specimen collection was after the patients had stopped treatments for a period of time. Thus, these differences in patient and blood collection time could cause inevitable bias to our results.…”

Molecular and Cellular Bases of Immunosenescence, Inflammation, and Cardiovascular Complications Mimicking “Inflammaging” in Patients with Systemic Lupus Erythematosus

“…Complex etiological factors are involved in lupus pathogenesis, such as genetic predisposition [28,29,30,31], epigenetic post-transcriptional regulation [32,33,34,35,36], sex hormone imbalance [37,38], environmental stimulation [39,40], mental/psychological stresses [38], and other undefined factors [41]. Recently, many authors have demonstrated that mitochondrial dysfunctions [42,43,44,45,46], defective bioenergetics in immune cells, and abnormal immunometabolism [47,48] can induce structural and functional changes of biomolecules (proteins, lipids, nucleic acids, and glycoproteins) by oxidative and nitrosative stresses [49,50].…”

Transcriptomic and Epigenetic Alterations in Dendritic Cells Correspond With Chronic Kidney Disease in Lupus Nephritis

“…The upregulation was noted only for mDCs from moderate and severe LN. These data may suggest that epigenetic changes might be controlled by other pathways and mechanisms (2, 48, 49), with inconsiderable engagement of the above mentioned factors. DNA demethylation, relaxing chromatin structure, facilitates the access of transcription factors thus inducing transcriptions of genes.…”