Memory Regulatory T Cells as a Biomarker of Early Type 1 Diabetes

Type 1 diabetes (T1D) is the most common chronic autoimmune disease in children, driven by a breakdown in self-tolerance and T cell-mediated immune attack of pancreatic beta-cells. There are no biomarkers to effectively diagnose autoimmunity before disease onset and clinical symptom development. Here, we applied deep multiparametric immunophenotyping to compare immune landscapes in 38 patients with new-onset T1D, 24 siblings, and 18 healthy control participants (HCs). Patients with T1D underwent clinical and metabolic evaluations. Immune populations in fresh whole-blood samples were analyzed using a panel of 26 antibodies, detecting 39 different cell populations. Memory regulatory T cells (memory Tregs) were significantly increased in patients with T1D (P < 0.05) and their siblings (P < 0.01) compared with HCs but not between patients with T1D and siblings. Memory Tregs were associated with disease status and age in multivariable analysis. There was a positive correlation between age and memory Tregs in the HC and sibling groups but not in patients with T1D. Baseline memory Treg levels in siblings resembled those of patients with T1D. These findings highlight the existence of an age-independent, disease-specific immune fingerprint that could serve as a minimally invasive biomarker for early diagnosis and personalized immunotherapy. Further studies using functional and single-cells analysis are needed to confirm memory Tregs as a pathogenic trait.