Influence of Disease Duration on Circulating Levels of miRNAs in Children and Adolescents with New Onset Type 1 Diabetes

Abstract

The objective of this study was to identify circulating miRNAs affected by disease duration in newly diagnosed children with type 1 diabetes. Forty children and adolescents from The Danish Remission Phase Cohort were followed with blood samples drawn at 1, 3, 6, 12 and 60 months after diagnosis. Pancreatic autoantibodies were measured at each visit. Cytokines were measured only the first year. miRNA expression profiling was performed by RT-qPCR and quantified for 179 human plasma miRNAs. The effect of disease duration was analyzed by mixed models for repeated measurements, adjusted for sex and age. Eight miRNAs (hsa-miR-10b-5p, hsa-miR-17-5p, hsa-miR-30e-5p, hsa-miR-93-5p, hsa-miR-99a-5p, hsa-miR-125b-5p, hsa-miR-423-3p and hsa-miR-497-5p) were found to significantly change expression (adjusted p-value < 0.05) with disease progression. Three pancreatic autoantibodies ICA, IA-2A, GADA65 and 4 cytokines IL-4, IL-10, IL-21, IL-22 were associated with the miRNAs at different time points. Pathway analysis revealed association with various immune-mediated signaling pathways. Eight miRNAs, involved in immunological pathways changed expression levels during the first five years after diagnosis in children with type 1 diabetes, and were associated with variations in cytokine and pancreatic antibodies, suggesting a possible effect on the immunological processes in the early phase of the disease.

LncRNA MIAT Promotes Allergic Inflammation and Symptoms by Targeting MiR-10b-5p in Allergic Rhinitis Mice

“…33,34 A previous study suggested that hsa-miR-10b-5p has a possible effect on the immunological processes in the early phase of type 1 diabetes in newly diagnosed children and adolescents. 35 In this study, we found that miR-10b-5p agomiR decreased the numbers of nose-scratching and sneezing, alleviated eosinophils infiltration, and decreased the level of serum OVA-specific IgE and the production of the Th2 cytokine IL-4; moreover, it decreased the level of the proinflammatory factor IL-6, the production of the Th17 cytokine IL-17, and the percentage of Th17 cells in AR mice. Similarly, Chen et al 15 suggested that miR-10b overexpression suppresses IL-17A production by both total CD4 and differentiating Th17 cells in ankylosing spondylitis.…”

Baseline Assessment of Circulating MicroRNAs Near Diagnosis of Type 1 Diabetes Predicts Future Stimulated Insulin Secretion

“…Circulating miRNAs are stable and measurable in serum and plasma with similar results (5). Twenty-nine circulating miRNAs were associated with type 1 diabetes by two to eight studies (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24) (Supplementary Table 1), suggesting reproducible associations despite heterogeneity in study design, cohorts, assays, and analysis methods. Cellular miRNAs were also linked to both human and experimental diabetes (23,(25)(26)(27)(28)(29)(30).…”

The rs6505162 C>A polymorphism in themiRNA-423gene exhibits a protective element of coronary artery in a southern Chinese population with Kawasaki disease

“…(32) Alterations in the expression extent of 8 miRNAs including miRNA-423 participating in the immune pathway might be involved in the immune process in the early stages of diabetes, through the alterations of the four cytokines IL-4., IL-10, IL-21, IL-22 and three pancreatic autoantibodies IA-2A, ICA, GAD65A. (33) In membranous glomerulonephropathy upregulation of miRNA-423 had a certain significant association with down regulated IL6. (34)We found that the descending expression of the designated genes on proliferation and differentiation in myoblast was caused by the upregulated miR-423-5p suppressing the suppressor of fused homolog in expression.…”