Andersson Svärd Agnes, Maziarz Marlena, Ramelius Anita, Lundgren Markus, Lernmark Åke, Elding Larsson Helena
Department of Clinical Sciences, Lund University/CRC, Skåne University Hospital, 205 02, Malmö, Sweden.
J Transl Autoimmun. 2020 Apr 9;3:100052. doi: 10.1016/j.jtauto.2020.100052. eCollection 2020.
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, CD14CD16, 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 CD14CD16 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.
1型糖尿病的风险与HLA - DQ以及针对胰岛素、谷氨酸脱羧酶（GAD65）、胰岛素瘤相关蛋白 - 2（IA - 2）或锌转运体8（ZnT8）的β细胞自身抗体的出现密切相关。长期暴露于自身抗体可能与已知在慢性感染或自身免疫性疾病中发生的T细胞耗竭有关。据推测，自身抗体暴露可能会影响外周血细胞上HLA - DQ的表达，从而导致与1型糖尿病发病机制相关的T细胞耗竭。本研究的目的是在斯科讷糖尿病预测（DiPiS）研究中，通过1）横断面分析或2）长期随访期间自身抗体轨迹下的累积面积（作为自身免疫负担的一种表达），确定自身抗体暴露是否与外周血细胞HLA - DQ细胞表面表达相关。对67名年龄在10 - 15岁的儿童进行了全血细胞计数、HLA - DQ细胞表面中位荧光强度（MFI）、自身抗体频率分析，并通过下一代测序分析了HLA基因型。在CD16、CD14CD16、CD4和CD8细胞中观察到随着自身抗体数量增加HLA - DQ细胞表面MFI降低，但在CD19细胞和中性粒细胞中未观察到。HLA - DQ细胞表面MFI在CD4 T细胞中与HLA - DQ2/8相关，在CD14CD16单核细胞和CD8 T细胞中微弱相关。这些关联似乎与自身免疫负担有关。结果表明，HLA - DQ细胞表面表达与HLA和自身免疫负担有关。
