Decreased HLA-DQ expression on peripheral blood cells in children with varying number of beta cell autoantibodies
(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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- author
- Andersson Svärd, Agnes LU ; Maziarz, Marlena LU ; Ramelius, Anita LU ; Lundgren, Markus LU ; Lernmark, Åke LU and Elding Larsson, Helena LU
- author collaboration
- organization
- publishing date
- 2020
- 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}}, }