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

Agnes Andersson Svärd; Marlena Maziarz; Anita Ramelius; Markus Lundgren; Åke Lernmark; Helena Elding Larsson; DiPiS study group

doi:10.1016/j.jtauto.2020.100052

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

J Transl Autoimmun. 2020 Apr 9:3:100052. doi: 10.1016/j.jtauto.2020.100052. eCollection 2020.

Authors

Agnes Andersson Svärd¹, Marlena Maziarz¹, Anita Ramelius¹, Markus Lundgren¹, Åke Lernmark¹, Helena Elding Larsson¹; DiPiS study group

Collaborators

DiPiS study group:
C Andersson, R Bennet, I Jönsson, M Ask, J Bremer, C Brundin, C Cilio, C Hansson, G Hansson, S Ivarsson, B Jonsdottir, B Lindberg, B Lernmark, J Melin, A Carlsson, E Cedervall, B Jönsson, K Larsson, J Neiderud

Affiliation

¹ Department of Clinical Sciences, Lund University/CRC, Skåne University Hospital, 205 02, Malmö, Sweden.

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 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.

Keywords: Autoantibodies; Autoimmunity; Cell surface imunofluorescence; Human Leukocyte antigen; Type 1 diabetes.