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瑞典 TEDDY 儿童中与 1 型糖尿病风险增加相关的白细胞、中性粒细胞和红细胞计数减少与性别、HLA 和胰岛自身抗体有关。

Reduction in White Blood Cell, Neutrophil, and Red Blood Cell Counts Related to Sex, HLA, and Islet Autoantibodies in Swedish TEDDY Children at Increased Risk for Type 1 Diabetes.

机构信息

Department of Clinical Sciences, Lund University/Clinical Research Centre, Skåne University Hospital, Malmö, Sweden

Health Informatics Institute, Department of Pediatrics, University of South Florida, Tampa, FL.

出版信息

Diabetes. 2018 Nov;67(11):2329-2336. doi: 10.2337/db18-0355. Epub 2018 Aug 13.

Abstract

Islet autoantibodies (IAs) precede the clinical onset of type 1 diabetes (T1D); however, the knowledge is limited about whether the prodrome affects complete blood counts (CBCs) in 4- to 12-year-old children with increased genetic risk for T1D. This study tested whether CBCs were altered in 4- to 12-year-old children without ( = 376) or with one or several IAs against insulin, GAD65, or IA-2 ( = 72). CBC was analyzed during longitudinal follow-up in 448 Swedish children enrolled in The Environmental Determinants of Diabetes in the Young (TEDDY) study. A linear mixed-effects model was used to assess potential association between IA and CBC measurements over time. The white blood cell and neutrophil counts were reduced in children with IAs, primarily in boys. In contrast, girls had lower levels of hemoglobin and hematocrit. Positivity for multiple IAs showed the lowest counts in white blood cells and neutrophils in boys and red blood cells, hemoglobin, and hematocrit in girls. These associations were primarily observed in children with the HLA-DR3-DQ2/DR4-DQ8 genotype. We conclude that the reduction in neutrophils and red blood cells in children with multiple IAs and HLA-DR3-DQ2/DR4-DQ8 genotype may signal a sex-dependent islet autoimmunity detected in longitudinal CBCs.

摘要

胰岛自身抗体 (IAs) 先于 1 型糖尿病 (T1D) 的临床发病;然而,对于增加 T1D 遗传风险的 4 至 12 岁儿童,前驱期是否会影响全血细胞计数 (CBC),相关知识有限。本研究检测了在 4 至 12 岁无(=376)或有 1 种或多种针对胰岛素、GAD65 或 IA-2 的自身抗体(=72)的儿童中,CBC 是否发生改变。在瑞典儿童中进行的环境决定糖尿病的年轻人 (TEDDY) 研究中,在纵向随访期间分析了 CBC。使用线性混合效应模型评估了 IA 与 CBC 测量值随时间的潜在关联。在有自身抗体的儿童中,白细胞和中性粒细胞计数减少,主要是男孩。相比之下,女孩的血红蛋白和血细胞比容较低。多种自身抗体阳性的男孩的白细胞和中性粒细胞计数以及女孩的红细胞、血红蛋白和血细胞比容最低。这些关联主要在 HLA-DR3-DQ2/DR4-DQ8 基因型的儿童中观察到。我们得出结论,多个自身抗体和 HLA-DR3-DQ2/DR4-DQ8 基因型的儿童中性粒细胞和红细胞减少可能表明在纵向 CBC 中检测到的性别依赖性胰岛自身免疫。

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