在斯科讷糖尿病预测研究（DiPiS）中，自身免疫性甲状腺疾病与儿童期 1 型糖尿病高危人群胰岛自身抗体的关系。
Childhood thyroid autoimmunity and relation to islet autoantibodies in children at risk for type 1 diabetes in the diabetes prediction in skåne (DiPiS) study.
机构信息
a Department of Clinical Sciences Malmö , Skåne University Hospital, Lund University , Malmo , Sweden.
b Department of Laboratory Medicine , Lund University , Lund , Sweden.
出版信息
Autoimmunity. 2018 Aug;51(5):228-237. doi: 10.1080/08916934.2018.1519027.
BACKGROUND
The aim was to determine prevalence and age at seroconversion of thyroid autoimmunity in relation to islet autoantibodies, gender and HLA-DQ genotypes in children with increased risk for type 1 diabetes followed from birth.
METHODS
In 10-year-old children (n = 1874), blood samples were analysed for autoantibodies against thyroid peroxidase (TPOAb), thyroglobulin (TGAb), glutamic acid decarboxylase 65 (GADA), Zink transporter 8 (ZnT8R/W/QA), insulinoma-associated protein-2 (IA-2A), insulin (IAA) and HLA-DQ genotypes. Prospectively collected samples from 2 years of age were next analysed for TPOAb, and TGAb and, finally, in confirming samples at 11-16 years of age along with TSH and FT4. Frequencies were tested with Chi-square or Fischer's exact tests, autoantibody levels with Wilcoxon and correlations between autoantibody levels with Spearman's rank correlation test.
RESULTS
The prevalence of thyroid autoimmunity was 6.9%, overrepresented in girls (p < .001) also having higher TPOAb levels at 10 years (p = .049). TPOAb was associated with GADA (p = .002), ZnT8R/W/QA (p = .001) and IA-2A (p = .001) while TGAb were associated with ZnT8R/W/QA (p = .021). In boys only, TPOAb were associated with GADA (p = .002), IA-2A (p = .001), ZnT8R/W/QA (p = .001) and IAA (p = .009), and TGAb with GADA (p = .013), IA-2A (p = .005) and ZnT8R/W/QA (p = .003). Levels of IA-2A correlated to both TPOAb (p = .021) and to TGAb (p = .011). In boys only, levels of GADA and TGAb correlated (p = .009 as did levels of IA-2A and TPOAb (p = .013). The frequency and levels of thyroid autoantibodies increased with age. At follow-up, 22.3% had abnormal thyroid function or were treated with thyroxine.
CONCLUSIONS
Thyroid autoimmunity and high TPOAb levels were more common in girls. In contrast, in boys only, there was a strong association with as well as correlation between levels of thyroid and islet autoantibodies. It is concluded that while girls may develop autoimmune thyroid disease (AITD) independent of islet autoantibodies, the risk for thyroid disease in boys may be linked to concomitant islet autoimmunity.
背景
本研究旨在确定在从出生开始随访的具有 1 型糖尿病风险的儿童中，与胰岛自身抗体、性别和 HLA-DQ 基因型相关的甲状腺自身免疫的流行率和血清转换年龄。
方法
在 10 岁儿童（n=1874）中，分析了针对甲状腺过氧化物酶（TPOAb）、甲状腺球蛋白（TGAb）、谷氨酸脱羧酶 65（GADA）、锌转运蛋白 8（ZnT8R/W/QA）、胰岛素瘤相关蛋白-2（IA-2A）、胰岛素（IAA）和 HLA-DQ 基因型的自身抗体。接下来，在 2 岁时检测前瞻性收集的样本中的 TPOAb 和 TGAb，最后在 11-16 岁时检测确诊样本以及 TSH 和 FT4。用卡方或 Fisher 精确检验检测频率，用 Wilcoxon 检验检测自身抗体水平，用 Spearman 秩相关检验检测自身抗体水平之间的相关性。
结果
甲状腺自身免疫的患病率为 6.9%，在女孩中更为常见（p<0.001），并且在 10 岁时 TPOAb 水平也更高（p=0.049）。TPOAb 与 GADA（p=0.002）、ZnT8R/W/QA（p=0.001）和 IA-2A（p=0.001）相关，而 TGAb 与 ZnT8R/W/QA（p=0.021）相关。仅在男孩中，TPOAb 与 GADA（p=0.002）、IA-2A（p=0.001）、ZnT8R/W/QA（p=0.001）和 IAA（p=0.009）相关，而 TGAb 与 GADA（p=0.013）、IA-2A（p=0.005）和 ZnT8R/W/QA（p=0.003）相关。IA-2A 的水平与 TPOAb（p=0.021）和 TGAb（p=0.011）相关。仅在男孩中，GADA 和 TGAb 的水平相关（p=0.009），IA-2A 和 TPOAb 的水平也相关（p=0.013）。甲状腺自身抗体的频率和水平随着年龄的增长而增加。随访时，22.3%的儿童甲状腺功能异常或接受甲状腺素治疗。
结论
在女孩中，甲状腺自身免疫和高 TPOAb 水平更为常见。相比之下，仅在男孩中，甲状腺和胰岛自身抗体的水平之间存在强烈的关联和相关性。研究结果表明，虽然女孩可能会发生与胰岛自身抗体无关的自身免疫性甲状腺疾病（AITD），但男孩发生甲状腺疾病的风险可能与同时存在的胰岛自身免疫有关。
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