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Decreased HLA-DQ expression on peripheral blood cells in children with varying number of beta cell autoantibodies

Andersson Svärd, Agnes LU orcid ; Maziarz, Marlena LU ; Ramelius, Anita LU ; Lundgren, Markus LU ; Lernmark, Åke LU orcid and Elding Larsson, Helena LU (2020) In Journal of Translational Autoimmunity 3.
Abstract

The risk for type 1 diabetes is strongly associated with HLA-DQ and the appearance of beta cell autoantibodies against either insulin, glutamate decarboxylase (GAD65), insulinoma-associated protein-2 (IA-2), or zinc transporter 8 (ZnT8). Prolonged exposure to autoantibodies may be related to T cell exhaustion known to occur in chronic infections or autoimmune disorders. It was hypothesized that autoantibody exposure may affect HLA-DQ expression on peripheral blood cells and thereby contribute to T cell exhaustion thought to be associated with the pathogenesis of type 1 diabetes. The aim of this study was to determine whether autoantibody exposure as an expression of autoimmunity burden was related to peripheral blood cell HLA-DQ cell... (More)

The risk for type 1 diabetes is strongly associated with HLA-DQ and the appearance of beta cell autoantibodies against either insulin, glutamate decarboxylase (GAD65), insulinoma-associated protein-2 (IA-2), or zinc transporter 8 (ZnT8). Prolonged exposure to autoantibodies may be related to T cell exhaustion known to occur in chronic infections or autoimmune disorders. It was hypothesized that autoantibody exposure may affect HLA-DQ expression on peripheral blood cells and thereby contribute to T cell exhaustion thought to be associated with the pathogenesis of type 1 diabetes. The aim of this study was to determine whether autoantibody exposure as an expression of autoimmunity burden was related to peripheral blood cell HLA-DQ cell surface expression in either 1) a cross-sectional analysis or 2) cumulative as area under the trajectory of autoantibodies during long term follow-up in the Diabetes Prediction in Skåne (DiPiS) study. Children (n = 67), aged 10-15 years were analyzed for complete blood count, HLA-DQ cell surface median fluorescence intensity (MFI), autoantibody frequency, and HLA genotypes by Next Generation Sequencing. Decreased HLA-DQ cell surface MFI with an increasing number of autoantibodies was observed in CD16+, CD14+CD16-, CD4+ and CD8+ cells but not in CD19+ cells and neutrophils. HLA-DQ cell surface MFI was associated with HLA-DQ2/8 in CD4+ T cells, marginally in CD14+CD16- monocytes and CD8+ T cells. These associations appeared to be related to autoimmunity burden. The results suggest that HLA-DQ cell surface expression was related to HLA and autoimmunity burden.

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; ; ; ; and
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Autoantibodies, Autoimmunity, Cell surface imunofluorescence, Human Leukocyte antigen, Type 1 diabetes
in
Journal of Translational Autoimmunity
volume
3
article number
100052
publisher
Elsevier
external identifiers
  • scopus:85089757224
  • pmid:32743532
ISSN
2589-9090
DOI
10.1016/j.jtauto.2020.100052
project
Immunological markers of type 1 diabetes pathogenesis prior to clinical diagnosis
language
English
LU publication?
yes
additional info
© 2020 The Authors.
id
34ed2993-2e6d-40c5-90b0-ca429e816b54
date added to LUP
2020-08-08 18:01:04
date last changed
2024-04-03 12:23:30
@article{34ed2993-2e6d-40c5-90b0-ca429e816b54,
  abstract     = {{<p>The risk for type 1 diabetes is strongly associated with HLA-DQ and the appearance of beta cell autoantibodies against either insulin, glutamate decarboxylase (GAD65), insulinoma-associated protein-2 (IA-2), or zinc transporter 8 (ZnT8). Prolonged exposure to autoantibodies may be related to T cell exhaustion known to occur in chronic infections or autoimmune disorders. It was hypothesized that autoantibody exposure may affect HLA-DQ expression on peripheral blood cells and thereby contribute to T cell exhaustion thought to be associated with the pathogenesis of type 1 diabetes. The aim of this study was to determine whether autoantibody exposure as an expression of autoimmunity burden was related to peripheral blood cell HLA-DQ cell surface expression in either 1) a cross-sectional analysis or 2) cumulative as area under the trajectory of autoantibodies during long term follow-up in the Diabetes Prediction in Skåne (DiPiS) study. Children (n = 67), aged 10-15 years were analyzed for complete blood count, HLA-DQ cell surface median fluorescence intensity (MFI), autoantibody frequency, and HLA genotypes by Next Generation Sequencing. Decreased HLA-DQ cell surface MFI with an increasing number of autoantibodies was observed in CD16+, CD14+CD16-, CD4+ and CD8+ cells but not in CD19+ cells and neutrophils. HLA-DQ cell surface MFI was associated with HLA-DQ2/8 in CD4+ T cells, marginally in CD14+CD16- monocytes and CD8+ T cells. These associations appeared to be related to autoimmunity burden. The results suggest that HLA-DQ cell surface expression was related to HLA and autoimmunity burden.</p>}},
  author       = {{Andersson Svärd, Agnes and Maziarz, Marlena and Ramelius, Anita and Lundgren, Markus and Lernmark, Åke and Elding Larsson, Helena}},
  issn         = {{2589-9090}},
  keywords     = {{Autoantibodies; Autoimmunity; Cell surface imunofluorescence; Human Leukocyte antigen; Type 1 diabetes}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{Journal of Translational Autoimmunity}},
  title        = {{Decreased HLA-DQ expression on peripheral blood cells in children with varying number of beta cell autoantibodies}},
  url          = {{http://dx.doi.org/10.1016/j.jtauto.2020.100052}},
  doi          = {{10.1016/j.jtauto.2020.100052}},
  volume       = {{3}},
  year         = {{2020}},
}