Distinct transcriptomic profiles in children prior to the appearance of type 1 diabetes-linked islet autoantibodies and following enterovirus infection
(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)
- author
- Lin, Jake
; Moradi, Elaheh
; Salenius, Karoliina
; Lehtipuro, Suvi
; Häkkinen, Tomi
; Laiho, Jutta E
; Oikarinen, Sami
; Randelin, Sofia
; Parikh, Hemang M
LU
; Krischer, Jeffrey P
; Toppari, Jorma
; Lernmark, Åke
LU
; Petrosino, Joseph F
; Ajami, Nadim J
; She, Jin-Xiong
; Hagopian, William A
; Rewers, Marian J
; Lloyd, Richard E
; Rautajoki, Kirsi J
; Hyöty, Heikki
and Nykter, Matti
(Less) - author collaboration
- organization
- publishing date
- 2023-11-22
- 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
- 2025-03-23 11:00:42
@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}},
}