自身报告的下呼吸道感染与 1 型糖尿病高危 HLA 基因型患儿胰岛自身免疫的发展：MIDIA 研究。

Self-reported lower respiratory tract infections and development of islet autoimmunity in children with the type 1 diabetes high-risk HLA genotype: the MIDIA study.

机构信息

Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway.

出版信息

Diabetes Metab Res Rev. 2011 Nov;27(8):834-7. doi: 10.1002/dmrr.1258.

DOI:10.1002/dmrr.1258

PMID:22069269

Abstract

AIM

To test whether self-reported lower respiratory tract infections in early infancy predicted risk for islet autoimmunity in genetically predisposed children.

METHODS

The environmental triggers for type 1 diabetes (MIDIA) study recruited newborns in Norway to identify those with the human leukocyte antigen high-risk genotype DR4-DQ8/DR3-DQ2. Of 46 939 newborns genotyped, 1003 (2.1%) carried the high-risk genotype, of whom 885 children were followed longitudinally with questionnaires and blood samples for autoantibody testing at 3, 6, 9 and 12 months of age, and then annually until 4 years of age. The endpoint (autoimmunity) was defined as positivity for at least one of three autoantibodies (to insulin, glutamic acid decarboxylase (GAD) or protein tyrosine phosphatase-like protein (IA2)) on at least two consecutive samples. The parents responded in the questionnaires, whether the child had had 'pneumonia, bronchitis or respiratory syncytial virus'. Cox proportional hazards regression models with time-dependent covariates were used to estimate hazard ratios for autoimmunity using STATA 10.

RESULTS

Forty-two children developed autoimmunity, of whom 15 later developed type 1 diabetes. For 17 of the 42 cases (40%) 'pneumonia, bronchitis or respiratory syncytial virus' was reported (0.5-4 years of age) before or at the onset of autoimmunity. For 187 of the 843 non-cases (22%) 'pneumonia, bronchitis or respiratory syncytial virus' was reported in the same age group. The hazard ratio was 3.4 (p=0.001, 95% confidence interval: 1.6-7.1) for developing autoimmunity. The estimated hazard ratio was only marginally influenced by adjustment for potential confounding factors. No association was found for other infectious self-reported symptoms.

CONCLUSION

Self-reported lower respiratory tract infections were associated with increased risk of islet autoimmunity in early infancy.

摘要

目的

检验婴儿早期下呼吸道感染是否会增加遗传易感性儿童发生胰岛自身免疫的风险。

方法

1 型糖尿病环境触发因素（MIDIA）研究在挪威招募了新生儿，以确定那些具有人类白细胞抗原高危基因型 DR4-DQ8/DR3-DQ2 的个体。在对 46939 名新生儿进行基因分型后，有 1003 名（2.1%）携带高危基因型，其中 885 名儿童进行了纵向随访，在 3、6、9 和 12 个月龄时通过问卷调查和血样进行自身抗体检测，然后每年检测一次，直至 4 岁。（自身免疫）终点定义为至少连续两次检测样本中至少有一种三种自身抗体（胰岛素、谷氨酸脱羧酶（GAD）或蛋白酪氨酸磷酸酶样蛋白（IA2））阳性。父母在问卷调查中回答了孩子是否“患有肺炎、支气管炎或呼吸道合胞病毒感染”。使用 STATA10，采用具有时间依赖性协变量的 Cox 比例风险回归模型，估计使用自身抗体的风险比。

结果

42 名儿童发生了自身免疫，其中 15 名随后发展为 1 型糖尿病。在 42 例病例中，有 17 例（40%）在自身免疫发病前或发病时报告了（0.5-4 岁）“肺炎、支气管炎或呼吸道合胞病毒感染”。在 843 名非病例中，有 187 例（22%）在相同年龄组报告了“肺炎、支气管炎或呼吸道合胞病毒感染”。发生自身免疫的风险比为 3.4（p=0.001，95%置信区间：1.6-7.1）。在调整潜在混杂因素后，估计的风险比仅略有影响。未发现其他感染性自报症状与风险比之间存在关联。