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

• Objective: The pathogenesis of type 1 diabetes (T1D) is associated with genetic predisposition and immunological changes during presymptomatic disease. Differences in 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. 

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

NATURVETENSKAP  -- Biologi -- Immunologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Immunology (hsv//eng)

Nyckelord

monocytes

type 1 diabetes

viral response

β-cell autoimmunity

autoantibody

interferon

Article

beta cell autoimmunity

case control study

child

chronic inflammation

cohort analysis

controlled study

cytokine response

differential gene expression

gene expression

gene set enrichment analysis

genetic transcription

human

human cell

insulin dependent diabetes mellitus

lymphocyte

monocyte

peripheral blood mononuclear cell

pilot study

RNA sequencing

transcriptomics

upregulation

virus infection

asymptomatic disease

autoimmunity

genetics

metabolism

mononuclear cell

Asymptomatic Diseases

Autoantibodies

Diabetes Mellitus

Type 1

Humans

Leukocytes

Mononuclear

Up-Regulation

Virus Diseases

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)