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

Journal of Translational Autoimmunity

Marlena Maziarz¹  E. Cedervall²  J. Melin³  C. Hansson³  C. Brundin³  B. Lernmark³  S. Ivarsson³  C. Cilio³  G. Hansson³  B. Jonsdottir³  A. Carlsson³  M. Ask³  I. Jönsson³  J. Bremer³  B. Lindberg³  R. Bennet³  C. Andersson⁴  Agnes Andersson Svärd⁴  Helena Elding Larsson⁴  Anita Ramelius⁴  Åke Lernmark⁴  Markus Lundgren⁴  J. Neiderud⁵  K. Larsson⁶  B. Jönsson⁷ 

[1] Corresponding author. Unit of Paediatric Endocrinology Clinical Research Center, Box 50 332, 202 13 Malmö Sweden.;Department of Clinical Sciences Lund, Lund University, Sweden;Department of Clinical Sciences Malmö, Lund University, Sweden;Department of Clinical Sciences, Lund University/CRC, Skåne University Hospital, 205 02, Malmö, Sweden;Department of Paediatrics, Kristianstad Central Hospital, Sweden;Department of Paediatrics, Ystad Hospital, Sweden;Department of Paediatrics, Ängelholm Hospital, Sweden;

关键词: Autoimmunity;    Type 1 diabetes;    Autoantibodies;    Human Leukocyte antigen;    Cell surface imunofluorescence;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown