Early childhood CMV infection may decelerate the progression to clinical type 1 diabetes
Early childhood CMV infection may decelerate the progression to clinical type 1 diabetes
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DOI：
10.1111/pedi.12788
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发表时间：
2019-02-01
影响因子：
3.4
通讯作者：
Lempainen, Johanna
中科院分区：
文献类型：
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作者：
Ekman, Ilse;Vuorinen, Tytti;Lempainen, Johanna
目的/假设巨细胞病毒（CMV）感染在1型糖尿病（T1 D）发病机制中的作用的证据仍然不确定。我们的目的是阐明巨细胞病毒感染在胰岛自身免疫的启动和人类白细胞抗原（HLA）赋予的T1 D风险的儿童中进展为临床T1 D的可能作用。方法对1402名来自前瞻性1型糖尿病预测和预防（DIPP）研究的儿童进行了儿童早期CMV特异性IgG抗体分析。所有儿童携带HLA-DQ基因型与T1 D风险增加相关。使用Kaplan-Meier生存分析和对数秩检验分析了CMV感染对T1 D相关自身抗体（胰岛素自身抗体[IAA]、谷氨酸脱羧酶[GADA]和胰岛素瘤抗原-2 [IA-2A]，n = 356）出现以及进展至临床T1 D（n = 233）的影响。结果儿童早期CMV感染与儿童期T1 D的发生呈负相关。早期CMV感染受试者中T1 D的累积进展减少（P = 0.035）。在进一步的分析中，分别检查了早期CMV感染对胰岛自身免疫启动和进展为临床T1 D的影响。有趣的是，早期CMV感染并不影响T1 D相关自身抗体的出现，但观察到从胰岛自身免疫到临床T1 D的进展速度减慢（P = 0.015）。结论我们的研究结果表明，儿童早期CMV感染可能会减缓胰岛自身免疫性疾病向临床T1 D的进展，从而可能保护这些儿童在儿童期发展为T1 D。
Aims/Hypothesis Evidence of the role of cytomegalovirus (CMV) infection in the pathogenesis of type 1 diabetes (T1D) has remained inconclusive. Our aim was to elucidate the possible role of CMV infection in the initiation of islet autoimmunity and in the progression to clinical T1D among children with human leukocyte antigen (HLA)-conferred T1D risk. Methods A total of 1402 children from the prospective Type 1 Diabetes Prediction and Prevention (DIPP) study were analyzed for CMV-specific IgG antibodies during early childhood. All the children carried HLA-DQ genotypes associated with increased risk for T1D. The effect of CMV infection on the appearance of T1D-associated autoantibodies (insulin autoantibodies [IAA], glutamic acid decarboxylase [GADA], and insulinoma antigen-2 [IA-2A], n = 356) and on the progression rate to clinical T1D (n = 233) were analyzed with Kaplan-Meier survival analysis and Log-rank test. Results Early childhood CMV infection was inversely associated with the development of T1D during childhood. Cumulative progression to T1D was decreased in subjects with an early CMV infection (P = 0.035). In further analyses, the effect of early CMV infection on the initiation of islet autoimmunity and progression to clinical T1D were examined separately. Interestingly, early CMV infection did not affect the appearance of T1D-associated autoantibodies but a decelerating effect was observed on the progression rate from islet autoimmunity to clinical T1D (P = 0.015). Conclusion Our results suggest that an early childhood CMV infection may decelerate the progression from islet autoimmunity to clinical T1D among at-risk children and may thus protect these children from progressing to T1D during childhood.