B/T-Zell-Rezeptor und Immun-Zell-Profiling auf Einzelzellebene bei Kindern mit hohem Typ 1 Diabetes Risiko
Kinder- und Jugendmedizin
Rheumatologie
Zusammenfassung der Projektergebnisse
Single cell RNA sequencing was performed on 1. Peripheral blood mononuclear cells from three time points (age 6 months, pre- and post-seroconversion) in children with high genetic risk for type 1 diabetes who developed islet autoantibodies or remained autoantibody negative during childhood; and 2. Peripheral blood mononuclear cells at baseline and after 3 months treatment from genetically susceptible, islet autoantibody negative children who received intranasal insulin or placebo in the PINIT trial. All data, including single cell RNA seq of memory CD4+ T cells. Memory CD8+ T cells, memory B cells, monocytes and cDCs, NK cells, pDCs, and hematopoietic stem cells processed and annotated. T Cell Receptor (TCR) sequences from the memory CD8+ T cells have been annotated. Analysis of single cell RNA seq data comparing 6-month samples from children who later seroconverted to islet autoantibody positive and children who remained islet autoantibody negative showed differences for most cell types, and in particular NK cells. Cluster analysis showed expansion of clusters representative of activated or responsive NK cells in the children who later developed islet autoantibodies. Differences subsided over time. These data suggest that very early events or responses to these events differ in children who later develop islet autoantibodies and that these differences do not persist throughout the pre-diabetic period. Memory CD8+ TCR sequence analyses in the children showed marked diversity and little evidence of large clonal expansion in the first years of life. A validation cohort remains to be processed and analyzed. Analyses of TCR and of the data from the children in the PINIT study will be completed in 2023.
Projektbezogene Publikationen (Auswahl)
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Reproducibility of 10x Genomics single cell RNA sequencing method in the immune cell environment. Journal of Immunological Methods, 502, 113227.
Kraus, Gloria; Weigelt, Marc; Reinhardt, Susanne; Petzold, Andreas; Dahl, Andreas & Bonifacio, Ezio
