Publication Date
11-22-2023
Journal
Nature Communications
DOI
10.1038/s41467-023-42763-9
PMID
37993433
PMCID
PMC10665402
PubMedCentral® Posted Date
11-22-2023
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Humans, Child, Autoantibodies, Diabetes Mellitus, Type 1, Transcriptome, Autoimmunity, Insulin, Enterovirus Infections, Islets of Langerhans
Abstract
Although the genetic basis and pathogenesis of type 1 diabetes have been studied extensively, how host responses to environmental factors might contribute to autoantibody development remains largely unknown. Here, we use longitudinal blood transcriptome sequencing data to characterize host responses in children within 12 months prior to the appearance of type 1 diabetes-linked islet autoantibodies, as well as matched control children. We report that children who present with insulin-specific autoantibodies first have distinct transcriptional profiles from those who develop GADA autoantibodies first. In particular, gene dosage-driven expression of GSTM1 is associated with GADA autoantibody positivity. Moreover, compared with controls, we observe increased monocyte and decreased B cell proportions 9-12 months prior to autoantibody positivity, especially in children who developed antibodies against insulin first. Lastly, we show that control children present transcriptional signatures consistent with robust immune responses to enterovirus infection, whereas children who later developed islet autoimmunity do not. These findings highlight distinct immune-related transcriptomic differences between case and control children prior to case progression to islet autoimmunity and uncover deficient antiviral response in children who later develop islet autoimmunity.
Included in
Endocrine System Diseases Commons, Endocrinology, Diabetes, and Metabolism Commons, Medical Microbiology Commons, Virology Commons
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