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新诊断 1 型糖尿病患儿的组织转谷氨酰胺酶自身抗体与人类白细胞抗原相关,但与胰岛自身抗体无关:一项瑞典全国前瞻性基于人群的队列研究。

Tissue transglutaminase autoantibodies in children with newly diagnosed type 1 diabetes are related to human leukocyte antigen but not to islet autoantibodies: A Swedish nationwide prospective population-based cohort study.

机构信息

a Department of Women's and Children's Health , Karolinska Institutet , Stockholm , Sweden.

b Hepatology and Nutrition , Astrid Lindgren Children's Hospital, Karolinska University Hospital , Stockholm , Sweden.

出版信息

Autoimmunity. 2018 Aug;51(5):221-227. doi: 10.1080/08916934.2018.1494160. Epub 2018 Nov 16.

Abstract

OBJECTIVES

This study explored the association between tissue transglutaminase autoantibody (tTGA), high-risk human leucocyte antigen (HLA) genotypes and islet autoantibodies in children with newly diagnosed type 1 diabetes (T1D).

PATIENTS AND METHODS

Dried blood spots and serum samples were taken at diagnosis from children <18 years of age participating in Better Diabetes Diagnosis (BDD), a Swedish nationwide prospective cohort study of children newly diagnosed with T1D. We analyzed tTGA, high-risk HLA DQ2 and DQ8 (DQX is neither DQ2 nor DQ8) and islet auto-antibodies (GADA, IA-2A, IAA, and three variants of Zinc transporter; ZnT8W, ZnT8R, and ZnT8QA).

RESULTS

Out of 2705 children diagnosed with T1D, 85 (3.1%) had positive tTGA and 63 (2.3%) had borderline values. The prevalence of tTGA was higher in children with the HLA genotypes DQ2/2, DQ2/X or DQ2/8 compared to those with DQ8/8 or DQ8/X (p = .00001) and those with DQX/X (p ≤ .00001). No significant differences were found in relation to islet autoantibodies or age at diagnosis, but the presence of tTGA was more common in girls than in boys (p = .018).

CONCLUSION

tTGA at T1D diagnosis (both positive and borderline values 5.4%) was higher in girls and in children homozygous for DQ2/2, followed by children heterozygous for DQ2. Only children with DQ2 and/or DQ8 had tTGA. HLA typing at the diagnosis of T1D can help to identify those without risk for CD.

摘要

目的

本研究旨在探讨组织转谷氨酰胺酶自身抗体(tTGA)、高危人类白细胞抗原(HLA)基因型与新诊断为 1 型糖尿病(T1D)儿童胰岛自身抗体之间的关系。

患者和方法

本研究纳入了参与瑞典全国性前瞻性队列研究 Better Diabetes Diagnosis(BDD)的新诊断为 T1D 的儿童,在诊断时采集了这些儿童的干血斑和血清样本。我们分析了 tTGA、高危 HLA DQ2 和 DQ8(DQX 既不是 DQ2 也不是 DQ8)和胰岛自身抗体(GADA、IA-2A、IAA 和三种锌转运体变体;ZnT8W、ZnT8R 和 ZnT8QA)。

结果

在 2705 名诊断为 T1D 的儿童中,85 名(3.1%)存在阳性 tTGA,63 名(2.3%)为边界值。与 DQ8/8 或 DQ8/X 以及 DQX/X 相比,HLA 基因型 DQ2/2、DQ2/X 或 DQ2/8 的儿童中 tTGA 的患病率更高(p=0.00001)。与胰岛自身抗体或诊断时的年龄相比,差异无统计学意义,但 tTGA 阳性患儿中女孩多于男孩(p=0.018)。

结论

T1D 诊断时 tTGA(阳性和边界值 5.4%)在女孩和 DQ2/2 纯合子儿童中更高,其次是 DQ2 杂合子儿童。只有携带 DQ2 和/或 DQ8 的儿童才有 tTGA。T1D 诊断时的 HLA 分型有助于识别无 CD 风险的人群。

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