Distinct transcriptomic profiles in children prior to the appearance of type 1 diabetes-linked islet autoantibodies and following enterovirus infection
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Published:2023-11-22
Issue:1
Volume:14
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Lin Jake, Moradi Elaheh, Salenius KaroliinaORCID, Lehtipuro Suvi, Häkkinen Tomi, Laiho Jutta E., Oikarinen Sami, Randelin Sofia, Parikh Hemang M.ORCID, Krischer Jeffrey P., Toppari JormaORCID, Lernmark ÅkeORCID, Petrosino Joseph F., Ajami Nadim J.ORCID, She Jin-Xiong, Hagopian William A.ORCID, Rewers Marian J.ORCID, Lloyd Richard E., Rautajoki Kirsi J.ORCID, Hyöty HeikkiORCID, Nykter MattiORCID,
Abstract
AbstractAlthough 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.
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
Reference80 articles.
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