University of Oulu

Valta, M, Yoshihara, M, Einarsdottir, E, et al. Viral infection-related gene upregulation in monocytes in children with signs of β-cell autoimmunity. Pediatr Diabetes. 2022; 23( 6): 703- 713. doi:10.1111/pedi.13346

Viral infection-related gene upregulation in monocytes in children with signs of β-cell autoimmunity

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Author: Valta, Milla1; Yoshihara, Masahito2; Einarsdottir, Elisabet3;
Organizations: 1Immunogenetics Laboratory, Institute of Biomedicine, University of Turku, Turku, Finland
2Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden
3Science for Life Laboratory, Department of Gene Technology, KTH-Royal Institute of Technology, Solna, Sweden
4Stem Cells and Metabolism Research Program, University of Helsinki, and Folkhälsan Research Center, Helsinki, Finland
5Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
6Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
7Folkhälsan Research Center, Helsinki, Finland
8Department of Pediatrics, Tampere University Hospital, Tampere, Finland
9Department of Pediatrics, PEDEGO Research Unit, MRC Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
10Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, University of Turku, Turku, Finland
11Department of Pediatrics, University of Turku and Turku University Hospital, Turku, Finland
12Clinical Microbiology, Turku University Hospital, Turku, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.2 MB)
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Language: English
Published: John Wiley & Sons, 2022
Publish Date: 2022-10-05


Objective: The pathogenesis of type 1 diabetes (T1D) is associated with genetic predisposition and immunological changes during presymptomatic disease. Differencesin immune cell subset numbers and phenotypes between T1D patients and healthy controls have been described; however, the role and function of these changes in the pathogenesis is still unclear. Here we aimed to analyze the transcriptomic landscapes of peripheral blood mononuclear cells (PBMCs) during presymptomatic disease.

Methods: Transcriptomic differences in PBMCs were compared between cases positive for islet autoantibodies and autoantibody negative controls (9 case–control pairs)and further in monocytes and lymphocytes separately in autoantibody positive subjects and control subjects (25 case–control pairs).

Results: No significant differential expression was found in either data set. However, when gene set enrichment analysis was performed, the gene sets “defence response to virus” (FDR <0.001, ranking 2), “response to virus” (FDR <0.001, ranking 3) and “response to type I interferon” (FDR=0.002, ranking 12) were enriched in the upregulated genes among PBMCs in cases. Upon further analysis, this was also seen in monocytes in cases (FDR=0.01, ranking 2; FDR=0.04, ranking 3 and FDR=0.02, ranking 1, respectively) but not in lymphocytes.

Conclusion: Gene set enrichment analysis of children with T1D-associated autoimmunity revealed changes in pathways relevant for virus infection in PBMCs, particularly in monocytes. Virus infections have been repeatedly implicated in the pathogenesis of T1D. These results support the viral hypothesis by suggesting altered immune activation of viral immune pathways in monocytes during diabetes.

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Series: Pediatric diabetes
ISSN: 1399-543X
ISSN-E: 1399-5448
ISSN-L: 1399-543X
Volume: 23
Issue: 6
Pages: 703 - 713
DOI: 10.1111/pedi.13346
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
3123 Gynaecology and paediatrics
Funding: Academy of Finland, Grant/Award Number: 292538; Astellas Foundation for Research on Metabolic Disorders; Centre of Excellence in Molecular Systems Immunology and Physiology Research 2012-2017, Grant/Award Number: 250114; Diabetestutkimussäätiö; European Commission, Grant/Award Number: BMH4-CT98-3314; Jane ja Aatos Erkon Säätiö; Japan Eye Bank Association; Japan Society for the Promotion of Science; Juvenile Diabetes Research Foundation International (DIPP study), Grant/Award Number: 1-SRA-2016-342-M-R 1-SRA-2019-732-M-B; Lastentautien Tutkimussäätiö; Novo Nordisk Fonden; Päivikki ja Sakari Sohlbergin Säätiö; Scandinavia-Japan Sasakawa Foundation; Sigrid Juséliuksen Säätiö; Special Research Funds for University Hospitals in Finland.
Copyright information: © 2022 The Authors. Pediatric Diabetes published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.