Serum exosomal miR‑328, miR‑575, miR‑134 and miR‑671‑5p as potential biomarkers for the diagnosis of Kawasaki disease and the prediction of therapeutic outcomes of intravenous immunoglobulin therapy

Abstract

The present study was conducted to screen serum exosomal microRNAs (miRNAs) for the early diagnosis of Kawasaki disease (KD) and to investigate their underlying mechanisms by analyzing microarray data under accession numbers GSE60965 [exosomal miRNA, including three pooled serum samples from 5 healthy children, 5 patients with KD and 5 patients with KD following intravenous immunoglobulin (IVIG) therapy] and GSE73577 (mRNA, including peripheral blood mononuclear cell samples from 19 patients with KD prior to and following IVIG treatment) from the Gene Expression Omnibus database. Differentially expressed miRNAs (DE-miRNAs) and genes (DEGs) were identified using the Linear Models for Microarray data method, and the mRNA targets of DE-miRNAs were predicted using the miRWalk 2.0 database. The functions of the target genes were analyzed using the Database for Annotation, Visualization and Integrated Discovery (DAVID). As a result, 65 DE-miRNAs were identified with different expression patterns between the healthy children and patients with KD and between patients with KD and patients with KD following IVIG therapy. The target genes of 15 common DE-miRNAs were predicted. Following overlapping the target genes of DE-miRNAs with 355 DEGs, 28 common genes were identified and further screened to construct a network containing 30 miRNA-mRNA regulatory associations. Of these associations, only miR-328-spectrin α, erythrocytic 1, miR-575-cyclic AMP-responsive element-binding protein 5/b-1,4-galactosyltransferase 5/WD repeat and FYVE domain-containing 3/cystatin-A/C-X-C motif chemokine receptor 1/protein phosphatase 1 regulatory subunit 3B, miR-134-acyl-CoA synthetase long chain family member 1/C-type lectin domain family 1 member A and miR-671-5p-tripartite motif containing 25/leucine rich repeat kinase 2/kinesin family member 1B/leucine rich repeat neuronal 1 were involved in the negative regulation of gene expression. Functional analysis indicated that the identified target genes may be associated with inflammation. Accordingly, serum exosomal miR-328, miR-575, miR-134 and miR-671-5p may act as potential biomarkers for the diagnosis of KD and the prediction of outcomes of the IVIG therapy by influencing the expression of inflammatory genes.

Association between histopathological changes and expression of selected microRNAs in skin of adult patients with IgA vasculitis

“…A better understanding of the pathogenesis and treatment of IgAV and other primary systemic vasculitides has led to the identification of many potentially clinically relevant biomarkers, including miRNAs . Some of this work has focused on the efficacy of using miRNA expression as a marker for disease activity in anti‐neutrophil cytoplasmic antibody (ANCA)‐associated vasculitis, giant‐cell arteritis, Behçet’s disease, and Kawasaki disease …”

“…Plasma miR‐29a, miR‐34a, miR‐142‐3p, miR‐383, miR‐20a, miR‐92a and miR‐221 could separate patients with ANCA‐associated vasculitis from healthy controls . Also, different miRNA expression patterns were found in blood cells and sera of patients with Behçet’s disease (miR‐638, miR‐4488, and miR‐3591‐3p) and Kawasaki disease (miR‐328, miR‐575, miR‐134, and miR‐671‐5p) . Only a few studies so far have focused on miRNA expression in tissues affected by vasculitis.…”

“…11 Some of this work has focused on the efficacy of using miRNA expression as a marker for disease activity in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, 12 giant-cell arteritis, 13 Behc ßet's disease, 14 and Kawasaki disease. 15 To the best our knowledge, no study has been performed on the associations between cutaneous histopathological changes and miRNA expression in IgAV. The highest significant association between miRNA expression and both the intensity of granulocyte infiltration and fibrinoid necrosis was found for the relative expression levels of miR-146a-5p, miR-203-3p, and miR-223-3p.…”

“…12 Also, different miRNA expression patterns were found in blood cells and sera of patients with Behc ßet's disease (miR-638, miR-4488, and miR-3591-3p) 14 and Kawasaki disease (miR-328, miR-575, miR-134, and miR-671-5p). 15 Only a few studies so far have focused on miRNA expression in tissues affected by vasculitis. In giant-cell arteritis, another different miRNA expression pattern was found in biopsy samples of temporal arteries: 13 miR-146b-5p, miR-146a, miR-155, miR-150, miR-21 and miR-299-5p were significantly overexpressed, and were associated with inflammatory processes driving the disease.…”

“…10 The discovery of microRNAs (miRNAs) as modulators of gene expression has resulted in extensive investigation of the ability of miRNAs to act as biomarkers in multisystem autoimmune disorders, including systemic vasculitides. [11][12][13][14][15][16] However, there is still a lack of information regarding miRNA expression in IgAV.…”