Norwegian Institute of Public Health, Oslo, Norway.
Diabetes Care. 2011 Jan;34(1):151-5. doi: 10.2337/dc10-1413. Epub 2010 Oct 7.
To test whether the frequency of human enterovirus RNA in fecal samples collected monthly from early infancy was associated with development of multiple islet autoantibodies in children with the highest risk HLA genotype.
Individuals carrying the HLA DRB10401-DQA103-DQB10302/DRB103-DQA105-DQB102 genotype were identified at birth and followed with monthly stool samples from age 3 to 35 months. Blood samples taken at age 3, 6, 9, and 12 months and then annually were tested for autoantibodies to insulin, GAD 65 and IA-2. Among 911 children, 27 developed positivity for two or more islet autoantibodies in two or more consecutive samples (case subjects). Two control subjects per case subject were matched by follow-up time, date of birth, and county of residence. Stool samples were analyzed for enterovirus with a semiquantitative real-time RT-PCR.
The frequency of human enterovirus RNA in stool samples from case subjects before seroconversion (43 of 339, 12.7%) did not differ from the frequency in control subjects (94 of 692, 13.6%) (P = 0.97). Results remained essentially unchanged after adjustment for potential confounders, restriction to various time windows before seroconversion, or infections in the 1st year of life or after inclusion of samples collected after seroconversion. There was no difference in the average quantity of enterovirus RNA or in the frequency of repeatedly positive samples. The estimated relative risk for islet autoimmunity per enterovirus RNA-positive sample during follow-up (nested case-control analysis) was 1.12 (95% CI 0.66-1.91).
There was no support for the hypothesis that fecal shedding of enteroviral RNA is a major predictor of advanced islet autoimmunity.
检测在携带最高危 HLA 基因型的儿童中，从婴儿早期每月采集的粪便样本中人类肠道病毒 RNA 的频率是否与多种胰岛自身抗体的发展有关。
在出生时鉴定出携带 HLA DRB10401-DQA103-DQB10302/DRB103-DQA105-DQB102 基因型的个体，并从 3 至 35 个月龄开始每月采集粪便样本进行随访。在 3、6、9 和 12 个月龄以及之后每年采集血液样本，检测胰岛素、GAD65 和 IA-2 自身抗体。在 911 名儿童中，27 名儿童在两个或多个连续样本中出现两种或多种胰岛自身抗体阳性（病例组）。按照随访时间、出生日期和居住县，每例病例组匹配两名对照者。采用半定量实时 RT-PCR 分析粪便样本中的肠道病毒。
在病例组血清转换前（43 例中的 339 例，12.7%）的粪便样本中，人类肠道病毒 RNA 的频率与对照组（94 例中的 692 例，13.6%）没有差异（P=0.97）。在调整潜在混杂因素、限制血清转换前的各种时间窗口、或纳入血清转换后采集的样本后，结果基本保持不变。肠道病毒 RNA 的平均数量或反复阳性样本的频率没有差异。在随访期间（巢式病例对照分析），每例肠道病毒 RNA 阳性样本发生胰岛自身免疫的相对风险估计值为 1.12（95%CI 0.66-1.91）。
没有证据支持肠道病毒 RNA 的粪便排出是晚期胰岛自身免疫的主要预测因素这一假说。
