Type 1 diabetes could begin with alterations in innate anti-viral immunity, which are already at this stage associated with HLA risk haplotypes

Karsten Buschard; Mathias Høj Jensen; Lars Krogvold; Ivan C Gerling; Knut Dahl-Jørgensen; Kristina Pedersen; Martin Haupt-Jorgensen

doi:10.1002/dmrr.3678

Type 1 diabetes could begin with alterations in innate anti-viral immunity, which are already at this stage associated with HLA risk haplotypes

Diabetes Metab Res Rev. 2023 Oct;39(7):e3678. doi: 10.1002/dmrr.3678. Epub 2023 Jul 3.

Authors

Karsten Buschard¹, Mathias Høj Jensen¹, Lars Krogvold², Ivan C Gerling³, Knut Dahl-Jørgensen^{2

4}, Kristina Pedersen¹, Martin Haupt-Jorgensen¹

Affiliations

¹ Department of Pathology, The Bartholin Institute, Rigshospitalet, Copenhagen, Denmark.
² Division of Paediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway.
³ Department of Medicine, University of Tennessee, Memphis, Tennessee, USA.
⁴ Faculty of Medicine, University of Oslo, Oslo, Norway.

PMID: 37395313
DOI: 10.1002/dmrr.3678

Abstract

Aims: To investigate if HLA risk haplotypes and HbA1c levels are associated with the expression levels of innate anti-viral immune pathway genes in type 1 diabetes.

Materials and methods: We investigated RNA expression levels of innate anti-viral immune pathway genes in laser-dissected islets from two to five tissue sections per donor from the Diabetes Virus Detection study and the network of Pancreatic Organ Donors in relation to HLA risk haplotypes (non-predisposed and predisposed) and HbA1c levels (normal, elevated, and high).

Results: The expression of innate anti-viral immune genes (TLR7, OAS1, OAS3 etc.) was significantly increased in individuals with predisposing vs non-predisposing HLA haplotypes. Also, the expression of several of the innate anti-viral immune genes from the HLA risk haplotype analysis was significantly increased in the group with high vs normal HbA1c. Furthermore, the gene expression of OAS2 was significantly increased in the group with high HbA1c vs elevated HbA1c.

Conclusions: Expression of innate anti-viral immune pathway genes was increased in individuals with predisposing HLA risk haplotypes and those with high HbA1c. This indicates that type 1 diabetes might well begin with alterations in innate anti-viral immunity, and already at this stage be associated with HLA risk haplotypes.

Keywords: HLA distribution; HbA1c; TLR7; enterovirus; innate antiviral immunity; type 1 diabetes.