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Åke Lernmark

Principal investigator

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

Author

  • Agnes Andersson Svärd
  • Marlena Maziarz
  • Anita Ramelius
  • Markus Lundgren
  • Åke Lernmark
  • Helena Elding Larsson

Summary, in English

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.

Department/s

  • Paediatric Endocrinology
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • Diabetes and Celiac Unit
  • Diabetic Complications

Publishing year

2020

Language

English

Publication/Series

Journal of Translational Autoimmunity

Volume

3

Document type

Journal article

Publisher

Elsevier

Topic

  • Pediatrics
  • Immunology in the medical area

Keywords

  • Autoantibodies
  • Autoimmunity
  • Cell surface imunofluorescence
  • Human Leukocyte antigen
  • Type 1 diabetes

Status

Published

Research group

  • Paediatric Endocrinology
  • Diabetes and Celiac Unit
  • Diabetic Complications

ISBN/ISSN/Other

  • ISSN: 2589-9090