P-311: An immune cell atlas of children recently diagnosed with type 1 diabetes using high-dimensional flow-cytometry
S Jalali, T Sutherland, J Schiesser, J Lego, S Mannering, E Stanley, F Cameron, D Pellicci, J Wentworth, T KayAbstract
Introduction
Type 1 diabetes (T1D) is an autoimmune disease characterised by immune-mediated destruction of pancreatic β-cells. Although alterations in selected circulating immune cell populations have been reported in newly diagnosed T1D (NDT1D), the extent of immune dysregulation across the broader immune system remains poorly understood
Objectives
We hypothesised that disease onset is associated with distinct immune lineage trajectories reflecting the underlying immunopathology of paediatric NDT1D. We therefore comprehensively profiled adaptive and innate immune cells using high-dimensional spectral flow-cytometry
Methods
Peripheral blood mononuclear cells from 55 paediatric NDT1D and 54 age- and sex-matched healthy controls (5-16 years) were analysed using a 45-parameter spectral flow cytometry panel. >100 immune cell populations were analysed and compared between groups
Results
NDT1D was characterised by extensive immune remodelling. Within the adaptive compartment, frequencies of B cells, TFH, Th17 cells, and TCM CD4+ and CD8+ T cells were increased, whereas TEM and TEMRA CD8+ T cells were reduced. Unconventional T cells, including MAIT, Vδ2+, and Vδ2– γδ T cells, were consistently decreased. The innate compartment showed reduced frequencies of CD56dim and CD56bright NK cells, plasmacytoid DCs and cDC1, monocytes, and ILC1, while ILC3 were increased. Increased CCR4 and CCR6 expression together with the increase of HLADR across T cell subsets indicated enhanced activation and tissue migratory potential
Conclusions
Our study’s novel findings, generated through comprehensive profiling of >100 types of immune cells, reveal a previously unrecognised organisation of the immune response in paediatric NDT1D, demonstrating that disease onset is characterised by coordinated remodelling across adaptive and innate immune compartments. These findings redefine early immune dysregulation as a systems-level process, providing a framework for precision immune monitoring and identifying candidate pathways for therapeutic targeting