The appearance of Type 1 diabetes (T1D)-associated autoantibodies is the
first and only measurable parameter to predict progression toward T1D
in genetically susceptible individuals. However, autoantibodies indicate
an active autoimmune reaction, wherein the immune tolerance is already
broken. Therefore, there is a clear and urgent need for new biomarkers
that predict the onset of the autoimmune reaction preceding autoantibody
positivity or reflect progressive beta-cell destruction. Here we report
the mRNA-sequencing-based analysis of 306 samples including
fractionated samples of CD4+ and CD8+ T cells as well as CD4-CD8- cells
fractions and unfractionated PBMC samples longitudinally collected from
seven children that developed beta-cell autoimmunity (Cases) at a young
age and their matched controls. We identified transcripts, including
interleukin-32 (IL32) that were upregulated before T1D-associated
autoantibodies appeared. Single-cell RNA-seq studies revealed that high
IL32 in Case samples were contributed mainly by activated T cells and
NK cells. Further, we showed that IL32 expression can be induced by a
virus and cytokines in pancreatic islets and beta-cells, respectively.
The results provide a basis for early detection of aberrations in the
immune system function before T1D and suggest a potential role for IL32 in the pathogenesis of T1D.