Enterovirus-associated changes in blood transcriptomic profiles of children with genetic susceptibility to type 1 diabetes

A1 Originalartikel i en vetenskaplig tidskrift (referentgranskad)


Interna författare/redaktörer


Publikationens författare: Lietzen Niina; An Le T. T.; Jaakkola Maria K.; Kallionpää Henna; Oikarinen Sami; Mykkänen Juha; Knip Mikael; Veijola Riitta; Ilonen Jorma; Toppari Jorma; Hyoty Heikki; Lahesmaa Riitta; Elo Laura L.
Förläggare: SPRINGER
Publiceringsår: 2018
Tidskrift: Diabetologia
Tidskriftsakronym: DIABETOLOGIA
Volym: 61
Nummer: 2
Artikelns första sida, sidnummer: 381
Artikelns sista sida, sidnummer: 388
Antal sidor: 8
ISSN: 0012-186X


Abstrakt

Aims/hypothesis Enterovirus infections have been associated with the development of type 1 diabetes in multiple studies, but little is known about enterovirus-induced responses in children at risk for developing type 1 diabetes. Our aim was to use genome-wide transcriptomics data to characterise enterovirus-associated changes in whole-blood samples from children with genetic susceptibility to type 1 diabetes.Methods Longitudinal whole-blood samples (356 samples in total) collected from 28 pairs of children at increased risk for developing type 1 diabetes were screened for the presence of enterovirus RNA. Seven of these samples were detected as enterovirus-positive, each of them collected from a different child, and transcriptomics data from these children were analysed to understand the individual-level responses associated with enterovirus infections. Transcript clusters with peaking or dropping expression at the time of enterovirus positivity were selected as the enterovirus-associated signals.Results Strong signs of activation of an interferon response were detected in four children at enterovirus positivity, while transcriptomic changes in the other three children indicated activation of adaptive immune responses. Additionally, a large proportion of the enterovirus-associated changes were specific to individuals. An enterovirus-induced signature was built using 339 genes peaking at enterovirus positivity in four of the children, and 77 of these genes were also upregulated in human peripheral blood mononuclear cells infected in vitro with different enteroviruses. These genes separated the four enterovirus-positive samples clearly from the remaining 352 blood samples analysed.Conclusions/interpretation We have, for the first time, identified enterovirus-associated transcriptomic profiles in whole-blood samples from children with genetic susceptibility to type 1 diabetes. Our results provide a starting point for understanding the individual responses to enterovirus infections in blood and their potential connection to the development of type 1 diabetes.


Nyckelord

Clinical immunology, Prediction and prevention of type 1 diabetes

Senast uppdaterad 2019-15-07 vid 06:07