Nature子刊:肠道病毒感染与儿童胰岛自身免疫和1型糖尿病
创作:fang fang 审核:mildbreeze 01月01日
  • 纳入近500名胰岛自身免疫(IA)或1型糖尿病(T1D)患儿及其匹配对照,分析3月龄至疾病诊断期间的粪便病毒组;
  • 肠道病毒B(尤其是柯萨奇病毒B)的长期感染(而非多次短期感染),与发生IA密切相关,但与T1D无关;
  • 6月龄前感染人腺病毒C(HAdV-C),与IA和T1D的风险降低有关;
  • 多次/长期HAdV-F感染与IA风险增加有弱关联;
  • CXADR(胰岛β细胞表面的柯萨奇和腺病毒受体)基因区域中rs6517774-G等位基因的携带者,发生IA的风险增加。
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mildbreeze
破坏胰岛β细胞的自身免疫反应,可导致胰岛素分泌不足和1型糖尿病(T1D)。有研究显示,这种胰岛自身免疫的发生可能与病毒感染有关,比如某些能感染β细胞的肠道病毒。Nature Medicine近期发表了一项来自TEDDY队列的报告,对有T1D风险的儿童进行前瞻性分析,鉴定出与胰岛自身免疫和/或T1D风险相关的肠道病毒和参与抗病毒应答的遗传突变,为进一步设计实验来检验特定肠道病毒在胰岛自身免疫和T1D中的作用和机制,以及开发潜在的抗病毒预防方法,打下基础。
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Nature Medicine [IF:36.13]

Prospective virome analyses in young children at increased genetic risk for type 1 diabetes

对1型糖尿病遗传风险增加的幼儿进行前瞻性病毒组分析

10.1038/s41591-019-0667-0

2019-12-02, Article

Abstract & Authors:展开

Abstract:收起
Viruses are implicated in autoimmune destruction of pancreatic islet β cells, which results in insulin deficiency and type 1 diabetes (T1D)1,2,3,4. Certain enteroviruses can infect β cells in vitro5, have been detected in the pancreatic islets of patients with T1D6 and have shown an association with T1D in meta-analyses4. However, establishing consistency in findings across studies has proven difficult. Obstacles to convincingly linking RNA viruses to islet autoimmunity may be attributed to rapid viral mutation rates, the cyclical periodicity of viruses7 and the selection of variants with altered pathogenicity and ability to spread in populations. β cells strongly express cell-surface coxsackie and adenovirus receptor (CXADR) genes, which can facilitate enterovirus infection8. Studies of human pancreata and cultured islets have shown significant variation in enteroviral virulence to β cells between serotypes and within the same serotype9,10. In this large-scale study of known eukaryotic DNA and RNA viruses in stools from children, we evaluated fecally shed viruses in relation to islet autoimmunity and T1D. This study showed that prolonged enterovirus B rather than independent, short-duration enterovirus B infections may be involved in the development of islet autoimmunity, but not T1D, in some young children. Furthermore, we found that fewer early-life human mastadenovirus C infections, as well as CXADR rs6517774, independently correlated with islet autoimmunity.

First Authors:
Kendra Vehik

Correspondence Authors:
Kendra Vehik

All Authors:
Kendra Vehik,Kristian F Lynch,Matthew C Wong,Xiangjun Tian,Matthew C Ross,Richard A Gibbs,Nadim J Ajami,Joseph F Petrosino,Marian Rewers,Jorma Toppari,Anette G Ziegler,Jin-Xiong She,Åke Lernmark,Beena Akolkar,William A Hagopian,Desmond A Schatz,Jeffrey P Krischer,Heikki Hyöty,Richard E Lloyd,the TEDDY Study Group

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Nature Medicine期刊

A viral link for type 1 diabetes

2019-12-02

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大队列告诉你:儿童 T1D 的肠道病毒组

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