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Possible Relationship between the HLA-DRA1 Intron Haplotype of Three Single-Nucleotide Polymorphisms in Intron 1 of the HLA-DRA1 Gene and Autoantibodies in Children at Increased Genetic Risk for Autoimmune Type 1 Diabetes

Andersson Svärd, Agnes LU orcid ; Benatti, Elin LU ; Lundgren, Markus LU ; Lernmark, Ake LU orcid ; Maziarz, Marlena LU and Elding Larsson, Helena LU (2022) In ImmunoHorizons 6(8). p.614-629
Abstract
Recently, a haplotype of three single-nucleotide polymorphisms (tri-SNP) in intron 1 of the HLA-DRA1 gene was found to be strongly associated with type 1 diabetes risk in HLA-DR3/3 individuals. The tri-SNP reportedly function as “expression quantitative trait loci,” modulating HLA-DR and -DQ expression. The aim was to investigate HLA-DRA1 tri-SNPs in relation to extended HLA class II haplotypes and human peripheral blood cell HLA-DQ cell-surface median fluorescence intensity (MFI), the first-appearing islet autoantibody, and autoimmunity burden. A total of 67 healthy subjects (10–15 y) at increased HLA risk for type 1 diabetes and with (n = 54) or without (n = 13) islet autoantibodies were followed longitudinally in the Diabetes Prediction... (More)
Recently, a haplotype of three single-nucleotide polymorphisms (tri-SNP) in intron 1 of the HLA-DRA1 gene was found to be strongly associated with type 1 diabetes risk in HLA-DR3/3 individuals. The tri-SNP reportedly function as “expression quantitative trait loci,” modulating HLA-DR and -DQ expression. The aim was to investigate HLA-DRA1 tri-SNPs in relation to extended HLA class II haplotypes and human peripheral blood cell HLA-DQ cell-surface median fluorescence intensity (MFI), the first-appearing islet autoantibody, and autoimmunity burden. A total of 67 healthy subjects (10–15 y) at increased HLA risk for type 1 diabetes and with (n = 54) or without (n = 13) islet autoantibodies were followed longitudinally in the Diabetes Prediction in Skåne study. Among four tri-SNPs, AGG (n = 67), GCA (n = 47), ACG (n = 11), and ACA (n = 9), HLA-DQ cell-surface MFI on CD4+ T cells was lower in AGG than GCA (p = 0.030) subjects. Cumulative autoimmunity burden was associated with reduced HLA-DQ cell-surface MFI in AGG compared with GCA in CD16+ cells (p = 0.0013), CD4+ T cells (p = 0.0018), and CD8+ T cells (p = 0.016). The results suggest that HLA-DRA1 tri-SNPs may be related to HLA-DQ cell-surface expression and autoimmunity burden. (Less)
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author
; ; ; ; and
author collaboration
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
SNP genotyping, HLA, type 1 diabetes, islet autoantibodies
in
ImmunoHorizons
volume
6
issue
8
article number
8
pages
614 - 629
publisher
American Association of Immunologists
external identifiers
  • scopus:85136132084
  • pmid:35981747
ISSN
2573-7732
DOI
10.4049/immunohorizons.2200039
project
Immunological markers of type 1 diabetes pathogenesis prior to clinical diagnosis
Etiology of autoimmune (type 1) diabetes
language
English
LU publication?
yes
id
a883454b-a9f4-4b06-88bc-53a6fc644539
date added to LUP
2022-08-23 10:04:12
date last changed
2024-03-13 08:13:08
@article{a883454b-a9f4-4b06-88bc-53a6fc644539,
  abstract     = {{Recently, a haplotype of three single-nucleotide polymorphisms (tri-SNP) in intron 1 of the HLA-DRA1 gene was found to be strongly associated with type 1 diabetes risk in HLA-DR3/3 individuals. The tri-SNP reportedly function as “expression quantitative trait loci,” modulating HLA-DR and -DQ expression. The aim was to investigate HLA-DRA1 tri-SNPs in relation to extended HLA class II haplotypes and human peripheral blood cell HLA-DQ cell-surface median fluorescence intensity (MFI), the first-appearing islet autoantibody, and autoimmunity burden. A total of 67 healthy subjects (10–15 y) at increased HLA risk for type 1 diabetes and with (n = 54) or without (n = 13) islet autoantibodies were followed longitudinally in the Diabetes Prediction in Skåne study. Among four tri-SNPs, AGG (n = 67), GCA (n = 47), ACG (n = 11), and ACA (n = 9), HLA-DQ cell-surface MFI on CD4+ T cells was lower in AGG than GCA (p = 0.030) subjects. Cumulative autoimmunity burden was associated with reduced HLA-DQ cell-surface MFI in AGG compared with GCA in CD16+ cells (p = 0.0013), CD4+ T cells (p = 0.0018), and CD8+ T cells (p = 0.016). The results suggest that HLA-DRA1 tri-SNPs may be related to HLA-DQ cell-surface expression and autoimmunity burden.}},
  author       = {{Andersson Svärd, Agnes and Benatti, Elin and Lundgren, Markus and Lernmark, Ake and Maziarz, Marlena and Elding Larsson, Helena}},
  issn         = {{2573-7732}},
  keywords     = {{SNP genotyping; HLA; type 1 diabetes; islet autoantibodies}},
  language     = {{eng}},
  number       = {{8}},
  pages        = {{614--629}},
  publisher    = {{American Association of Immunologists}},
  series       = {{ImmunoHorizons}},
  title        = {{Possible Relationship between the HLA-DRA1 Intron Haplotype of Three Single-Nucleotide Polymorphisms in Intron 1 of the HLA-DRA1 Gene and Autoantibodies in Children at Increased Genetic Risk for Autoimmune Type 1 Diabetes}},
  url          = {{http://dx.doi.org/10.4049/immunohorizons.2200039}},
  doi          = {{10.4049/immunohorizons.2200039}},
  volume       = {{6}},
  year         = {{2022}},
}