Meta-Immunological Profiling of Children With Type 1 Diabetes Identifies New Biomarkers to Monitor Disease Progression

Abstract

Type 1 diabetes is characterized by autoimmune destruction of pancreatic β-cells in genetically susceptible individuals. Triggers of islet autoimmunity, time course, and the precise mechanisms responsible for the progressive β-cell failure are not completely understood. The recent escalation of obesity in affluent countries has been suggested to contribute to the increased incidence of type 1 diabetes. Understanding the link between metabolism and immune tolerance could lead to the identification of new markers for the monitoring of disease onset and progression. We studied several immune cell subsets and factors with high metabolic impact as markers associated with disease progression in high-risk subjects and type 1 diabetic patients at onset and at 12 and 24 months after diagnosis. A multiple correlation matrix among different parameters was evaluated statistically and assessed visually on two-dimensional graphs. Markers to predict residual β-cell function up to 1 year after diagnosis were identified in multivariate logistic regression models. The meta-immunological profile changed significantly over time in patients, and a specific signature that was associated with worsening disease was identified. A multivariate logistic regression model measuring age, BMI, fasting C-peptide, number of circulating CD3+CD16+CD56+ cells, and the percentage of CD1c+CD19−CD14−CD303− type 1 myeloid dendritic cells at disease onset had a significant predictive value. The identification of a specific meta-immunological profile associated with disease status may contribute to our understanding of the basis of diabetes progression.

Role of Metabolism in the Immunobiology of Regulatory T Cells

“…Experimental evidence (121, 122) shows that metabolic imbalance (i.e., overweight and obesity) can increase the risk of development of immune-mediated diseases such T1D and as multiple sclerosis. Unfortunately, a limitation in studying Treg cell metabolism is represented by their plasticity and differences according to source (human vs mouse), in vitro culture conditions (i.e., exogenous cytokines such as IL-2 and TGF-β), and TCR engagement.…”

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

“…It has been shown that in T1D subjects, the number of natural killer (NK), dendritic (DC), and T cell subsets is significantly altered compared to controls [17]. Moreover, the immunological profile significantly changes over time in T1D, and a specific peripheral immune cell signature can be associated with worsening disease [18].…”

Immune cell and cytokine patterns in children with type 1 diabetes mellitus undergoing a remission phase: A longitudinal study

“…Circulating immune cells in T1D patients may reflect the events occurring in the pancreas and may predict the occurrence of the remission phase, but prospective longitudinal data are limited. One study in children with T1D suggested that specific immunological signatures are related to disease severity and functional changes in circulating Treg have been reported at different disease stages …”