Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Distinct transcriptomic profiles in children prior to the appearance of type 1 diabetes-linked islet autoantibodies and following enterovirus infection

Lin, Jake ; Moradi, Elaheh ; Salenius, Karoliina ; Lehtipuro, Suvi ; Häkkinen, Tomi ; Laiho, Jutta E ; Oikarinen, Sami ; Randelin, Sofia ; Parikh, Hemang M LU and Krischer, Jeffrey P , et al. (2023) In Nature Communications 14. p.1-13
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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; and (Less)
author collaboration
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Humans, Child, Autoantibodies, Diabetes Mellitus, Type 1, Transcriptome, Autoimmunity/genetics, Insulin/metabolism, Enterovirus Infections/genetics, Islets of Langerhans/metabolism
in
Nature Communications
volume
14
article number
7630
pages
1 - 13
publisher
Nature Publishing Group
external identifiers
  • pmid:37993433
  • scopus:85177635181
ISSN
2041-1723
DOI
10.1038/s41467-023-42763-9
language
English
LU publication?
yes
additional info
© 2023. The Author(s).
id
1e6faca6-a204-43e3-a6f8-bd0fd6cbe590
date added to LUP
2023-11-25 17:32:04
date last changed
2024-02-18 15:47:36
@article{1e6faca6-a204-43e3-a6f8-bd0fd6cbe590,
  abstract     = {{<p>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.</p>}},
  author       = {{Lin, Jake and Moradi, Elaheh and Salenius, Karoliina and Lehtipuro, Suvi and Häkkinen, Tomi and Laiho, Jutta E and Oikarinen, Sami and Randelin, Sofia and Parikh, Hemang M and Krischer, Jeffrey P and Toppari, Jorma and Lernmark, Åke and Petrosino, Joseph F and Ajami, Nadim J and She, Jin-Xiong and Hagopian, William A and Rewers, Marian J and Lloyd, Richard E and Rautajoki, Kirsi J and Hyöty, Heikki and Nykter, Matti}},
  issn         = {{2041-1723}},
  keywords     = {{Humans; Child; Autoantibodies; Diabetes Mellitus, Type 1; Transcriptome; Autoimmunity/genetics; Insulin/metabolism; Enterovirus Infections/genetics; Islets of Langerhans/metabolism}},
  language     = {{eng}},
  month        = {{11}},
  pages        = {{1--13}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{Distinct transcriptomic profiles in children prior to the appearance of type 1 diabetes-linked islet autoantibodies and following enterovirus infection}},
  url          = {{http://dx.doi.org/10.1038/s41467-023-42763-9}},
  doi          = {{10.1038/s41467-023-42763-9}},
  volume       = {{14}},
  year         = {{2023}},
}