Enterovirus RNA in longitudinal blood samples and risk of islet autoimmunity in children with a high genetic risk of type 1 diabetes: the MIDIA study
Enterovirus RNA in longitudinal blood samples and risk of islet autoimmunity in children with a high genetic risk of type 1 diabetes: the MIDIA study
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DOI：
10.1007/s00125-014-3327-4
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发表时间：
2014-10-01
期刊：
影响因子：
8.2
通讯作者：
Ronningen, Kjersti S.
中科院分区：
文献类型：
--
作者：
Cinek, Ondrej;Stene, Lars C.;Ronningen, Kjersti S.
目的/假设肠病毒和胰岛自身免疫的纵向分子研究只有少数报道，阳性结果似乎仅限于芬兰。我们的目的是调查血液中的肠道病毒RNA和胰岛自身免疫之间的关联在MIDIA研究挪威，一个国家，在很大程度上共享的环境和经济特征与芬兰。方法我们分析了系列血液样本收集在年龄3，6和9个月，然后每年从45名儿童谁开发确认阳性至少两个自身抗体（针对胰岛素、GAD 65和IA-2）和92名匹配的对照，所有对照均来自具有单一高危HLA-DQ-DR基因型的儿童队列。结果在807份血液标本中，肠道病毒阳性72份，阳性率为8.9%。在胰岛自身抗体首次检测前（7.6%病例，10.0%对照，OR 0.75 [95%CI 0.36，1.57]）或首次检测后（10.5%病例，5.8%对照，OR 2.00 [95%CI 0.64，6.27]），肠道病毒RNA与胰岛自身免疫无相关性。然而，与匹配对照的相应时间点（3.2%，OR 8.7 [95% CI 0.97，77]）相比，第一份胰岛自身抗体阳性样本（15.8%）中肠道病毒检测频率有更高的趋势。这些结果都没有改变调整潜在的混杂因素，限制到各种时间间隔或采用各种定义的肠道病毒positive.Conclusions/解释肠道病毒RNA在血液中的阳性并不能预测以后诱导胰岛自身抗体，但肠道病毒往往被检测到更经常在胰岛自身抗体血清转换阶段。
Aims/hypothesis Only a few longitudinal molecular studies of enterovirus and islet autoimmunity have been reported, and positive results seem to be limited to Finland. We aimed to investigate an association between enterovirus RNA in blood and islet autoimmunity in the MIDIA study from Norway, a country which largely shares environmental and economic features with Finland.Methods We analysed serial blood samples collected at ages 3, 6, and 9 months and then annually from 45 children who developed confirmed positivity for at least two autoantibodies (against insulin, GAD65 and IA-2) and 92 matched controls, all from a cohort of children with a single high-risk HLA-DQ-DR genotype. Enterovirus was tested in RNA extracted from frozen blood cell pellets, using real-time RT-PCR with stringent performance control.Results Out of 807 blood samples, 72 (8.9%) were positive for enterovirus. There was no association between enterovirus RNA and islet autoimmunity in samples obtained strictly before (7.6% cases, 10.0% controls, OR 0.75 [95% CI 0.36, 1.57]), or strictly after the first detection of islet autoantibodies (10.5% case, 5.8% controls, OR 2.00 [95% CI 0.64, 6.27]). However, there was a tendency towards a higher frequency of enterovirus detection in the first islet autoantibody-positive sample (15.8%) compared with the corresponding time point in matched controls (3.2%, OR 8.7 [95% CI 0.97, 77]). Neither of these results was changed by adjusting for potential confounders, restricting to various time intervals or employing various definitions of enterovirus positivity.Conclusions/interpretation Positivity for enterovirus RNA in blood did not predict the later induction of islet autoantibodies, but enterovirus tended to be detected more often at the islet autoantibody seroconversion stage.