Blood Co-Circulating Extracellular microRNAs and Immune Cell Subsets Associate with Type 1 Diabetes Severity

• Published in: International journal of molecular sciences 2020-01, Vol.21 (2), p.477
• Main Authors: Garavelli, Silvia, Bruzzaniti, Sara, Tagliabue, Elena, Prattichizzo, Francesco, Di Silvestre, Dario, Perna, Francesco, La Sala, Lucia, Ceriello, Antonio, Mozzillo, Enza, Fattorusso, Valentina, Mauri, Pierluigi, Puca, Annibale A, Franzese, Adriana, Matarese, Giuseppe, Galgani, Mario, de Candia, Paola
• Format: Article
• Language: English
• Subjects: autoimmune; Biomarkers; Blood circulation; Body mass index; CD25 antigen; CD4 antigen; Children; Diabetes; Diabetes mellitus (insulin dependent); Diabetic ketoacidosis; Disease; Disease control; Flow cytometry; Hemoglobin; Immune system; Immunology; Insulin; Ketoacidosis; Lymphocytes; Lymphocytes B; MicroRNAs; miRNA; Pancreas; Peptides; Peripheral blood; Polymerase chain reaction; Regression analysis
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21020477

Immune cell subsets and microRNAs have been independently proposed as type 1 diabetes (T1D) diagnostic and/or prognostic biomarkers. Here, we aimed to analyze the relationships between peripheral blood circulating immune cell subsets, plasmatic microRNAs, and T1D. Blood samples were obtained from both children with T1D at diagnosis and age-sex matched healthy controls. Then, immunophenotype assessed by flow cytometry was coupled with the quantification of 60 plasmatic microRNAs by quantitative RT-PCR. The associations between immune cell frequency, plasmatic microRNAs, and the parameters of pancreatic loss, glycemic control, and diabetic ketoacidosis were assessed by logistic regression models and correlation analyses. We found that the increase in specific plasmatic microRNAs was associated with T1D disease onset (let-7c-5p, let-7d-5p, let-7f-5p, let-7i-5p, miR-146a-5p, miR-423-3p, and miR-423-5p), serum C-peptide concentration (miR-142-5p and miR-29c-3p), glycated hemoglobin (miR-26a-5p and miR-223-3p) and the presence of ketoacidosis (miR-29c-3p) more strongly than the evaluated immune cell subset frequency. Some of these plasmatic microRNAs were shown to positively correlate with numbers of blood circulating B lymphocytes (miR-142-5p) and CD4 CD45RO (miR-146a-5p and miR-223-3p) and CD4 CD25 cells (miR-423-3p and miR-223-3p) in children with T1D but not in healthy controls, suggesting a disease-specific microRNA association with immune dysregulation in T1D. In conclusion, our results suggest that, while blood co-circulating extracellular microRNAs and immune cell subsets may be biologically linked, microRNAs may better provide powerful information about T1D onset and severity.