Enterovirus exposure uniquely discriminates type 1 diabetes patients with a homozygous from a heterozygous melanoma differentiation-associated protein 5/interferon induced with helicase C domain 1A946T genotype

B.M. Schulte; P.R. Gielen; E.D. Kers-Rebel; A.C. Prosser; K. Lind; M. Flodström-Tullberg; C.J. Tack; L.D. Elving; G.J. Adema

doi:10.1089/vim.2015.0140

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Enterovirus exposure uniquely discriminates type 1 diabetes patients with a homozygous from a heterozygous melanoma differentiation-associated protein 5/interferon induced with helicase C domain 1A946T genotype

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Enterovirus exposure uniquely discriminates type 1 diabetes patients with a homozygous from a heterozygous melanoma differentiation-associated protein 5/interferon induced with helicase C domain 1A946T genotype

B.M. Schulte, P.R. Gielen, E.D. Kers-Rebel, A.C. Prosser, K. Lind, M. Flodström-Tullberg, C.J. Tack, L.D. Elving and G.J. Adema

Viral Immunology, Vol.29(7), pp.389-397

2016

DOI: https://doi.org/10.1089/vim.2015.0140

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Abstract

In children at risk for type 1 diabetes, innate immune activity is detected before seroconversion. Enterovirus infections have been linked to diabetes development, and a polymorphism (A946T) in the innate immune sensor recognizing enterovirus RNA, interferon-induced with helicase C domain 1/melanoma differentiation-associated protein 5, predisposes to disease. We hypothesized that the strength of innate antienteroviral responses is affected in autoimmune type 1 diabetes patients and linked to the A946T polymorphism. We compared induction of interferon-stimulated genes (ISGs) in peripheral blood mononuclear cells (PBMCs) and dendritic cells (DCs) in healthy individuals and diabetes patients upon stimulation with enterovirus, enterovirus-antibody complexes, or ligands mimicking infection in relation to the A946T polymorphism. Overall, PBMCs of diabetes patients and healthy donors showed comparable ISG induction upon stimulation. No differences were observed in DCs. Interestingly, the data imply that the magnitude of responses to enterovirus and enterovirus-antibody complexes in PBMCs is critically influenced by the A946T polymorphism and elevated in heterozygotes compared to TT homozygous individuals in autoimmune diabetes patients, but not healthy controls. These data imply an intrinsic difference in the responses to enterovirus and enterovirus-antibody complexes in diabetes patients carrying a TT risk genotype compared to heterozygotes that may influence control of enterovirus clearance

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Title: Enterovirus exposure uniquely discriminates type 1 diabetes patients with a homozygous from a heterozygous melanoma differentiation-associated protein 5/interferon induced with helicase C domain 1A946T genotype
Authors/Creators: B.M. Schulte (Author/Creator)
P.R. Gielen (Author/Creator)
E.D. Kers-Rebel (Author/Creator)
A.C. Prosser (Author/Creator)
K. Lind (Author/Creator)
M. Flodström-Tullberg (Author/Creator)
C.J. Tack (Author/Creator)
L.D. Elving (Author/Creator)
G.J. Adema (Author/Creator)
Publication Details: Viral Immunology, Vol.29(7), pp.389-397
Publisher: Mary Ann Liebert Publishers
Identifiers: 991005544805707891
Copyright: © 2016, Mary Ann Liebert, Inc.
Murdoch Affiliation: Institute for Immunology and Infectious Diseases
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.26 Diabetes; 1.26.1016 Type 1 Diabetes
Web Of Science research areas: Immunology; Virology
ESI research areas: Immunology