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Diabetes. 2019 Oct;68(10):2024-2034. doi: 10.2337/db19-0287. Epub 2019 Jul 16.

Early Detection of Peripheral Blood Cell Signature in Children Developing β-Cell Autoimmunity at a Young Age.

Author information

1
Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.
2
Department of Computer Science, Aalto University School of Science, Espoo, Finland.
3
Children's Hospital, University of Helsinki, and Helsinki University Hospital, Helsinki, Finland.
4
Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.
5
Department of Pediatrics, University of Tartu, Tartu, Estonia.
6
Children's Clinic of Tartu, Tartu University Hospital, Tartu, Estonia.
7
Research Programs Unit, Molecular Neurology and Biomedicum Stem Cell Centre, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
8
Department of Immunology, Genetics and Pathology, Uppsala University, Sweden.
9
Folkhälsan Research Center, Helsinki, Finland.
10
Tampere Center for Child Health Research, Tampere University Hospital, Tampere, Finland.
11
Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland riitta.lahesmaa@utu.fi.

Abstract

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 β-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- cell fractions and unfractionated peripheral blood mononuclear cell samples longitudinally collected from seven children who developed β-cell autoimmunity (case subjects) at a young age and matched control subjects. We identified transcripts, including interleukin 32 (IL32), that were upregulated before T1D-associated autoantibodies appeared. Single-cell RNA sequencing studies revealed that high IL32 in case samples was 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 β-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.

PMID:
31311800
DOI:
10.2337/db19-0287

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