病毒被认为是胰岛自身免疫(IA)和1型糖尿病(T1D)的主要候选触发因素,基于大量的流行病学和实验证据。最近的研究使用宏基因组下一代测序(mNGS)调查了所有病毒(“病毒基因”)与IA/T1D之间的关联。在Medline和EMBASE(发表于2000年至2020年6月)的人类观察研究的系统评价和荟萃分析中,分析了早期病毒与IA/T1D发展之间的当前关联。没有语言限制。纳入标准如下:队列和病例对照研究使用mNGS在发展为IA/T1D的≤18岁儿童的临床标本中检查病毒。使用国家卫生和医学研究委员会的证据量表和纽卡斯尔-渥太华量表进行研究评估。使用随机效应模型对暴露于特定病毒的Meta分析,使用比值比(ORs)和95%置信区间(CIs)测量关联强度.符合条件的研究(一个病例对照,9个嵌套病例对照)包括1,425名参与者(695例,730个对照)和检查IA(n=1,023)或T1D(n=402)。荟萃分析确定了IA与所有肠道病毒阳性的粪便样本数量之间的小但显着关联(OR1.14,95%CI1.00-1.29,p=0.05;异质性χ2=1.51,p=0.68,I2=0%),肠道病毒的连续阳性(1.55,1.09-2.20,p=0.01;χ2=0.19,p=0.91,I2=0%)和对肠道病毒B特异性阳性的粪便样本数量(1.20,1.01-1.42,p=0.04;χ2=0.03,p=0.86,I2=0%)。迄今为止的病毒学分析已经证明肠道病毒和IA之间的关联可能具有临床意义。然而,需要更大的前瞻性mNGS研究,更频繁的采样和妊娠后随访,以进一步阐明早期病毒暴露与IA/T1D之间的关联.
Viruses are postulated as primary candidate triggers of islet autoimmunity (IA) and type 1 diabetes (T1D), based on considerable epidemiological and experimental evidence. Recent studies have investigated the association between all viruses (the \'
virome\') and IA/T1D using metagenomic next-generation sequencing (mNGS). Current associations between the early life
virome and the development of IA/T1D were analysed in a systematic
review and meta-analysis of human observational studies from Medline and EMBASE (published 2000-June 2020), without language restriction. Inclusion criteria were as follows: cohort and case-control studies examining the
virome using mNGS in clinical specimens of children ≤18 years who developed IA/T1D. The National Health and Medical Research Council level of evidence scale and Newcastle-Ottawa scale were used for study appraisal. Meta-analysis for exposure to specific viruses was performed using random-effects models, and the strength of association was measured using odds ratios (ORs) and 95% confidence intervals (CIs). Eligible studies (one case-control, nine nested case-control) included 1,425 participants (695 cases, 730 controls) and examined IA (n = 1,023) or T1D (n = 402). Meta-analysis identified small but significant associations between IA and number of stool samples positive for all enteroviruses (OR 1.14, 95% CI 1.00-1.29, p = 0.05; heterogeneity χ2 = 1.51, p = 0.68, I2 = 0%), consecutive positivity for enteroviruses (1.55, 1.09-2.20, p = 0.01; χ2 = 0.19, p = 0.91, I2 = 0%) and number of stool samples positive specifically for enterovirus B (1.20, 1.01-1.42, p = 0.04; χ2 = 0.03, p = 0.86, I2 = 0%).
Virome analyses to date have demonstrated associations between enteroviruses and IA that may be clinically significant. However, larger prospective mNGS studies with more frequent sampling and follow-up from pregnancy are required to further elucidate associations between early virus exposure and IA/T1D.