4.7 Article

Detection of enterovirus RNA in peripheral blood mononuclear cells correlates with the presence of the predisposing allele of the type 1 diabetes risk gene IFIH1 and with disease stage

期刊

DIABETOLOGIA
卷 65, 期 10, 页码 1701-1709

出版社

SPRINGER
DOI: 10.1007/s00125-022-05753-y

关键词

Autoimmunity; Enterovirus; Genetic risk; IFIH-1; Interferon induced with helicase C domain 1; MDA5; Melanoma differentiation-associated protein 5; Pancreatic islets; rs1990760; Type 1 diabetes

资金

  1. centre grant Diabetes - Genes, Autoimmunity and Prevention (D-GAP) from the JDRF [1-2007-1803]
  2. JDRF Career Development Award [5-CDA-2014-221-A-N]
  3. JDRF [JDRF 25-2012-516, 4-SRA-2017-473-A-N]
  4. Medical Research Council [MR/P010695/1]
  5. Wellcome Trust [07212/A/15/Z]
  6. European Commission (Persistent Virus Infection in Diabetes Network [PEVNET] Frame Programme 7 [261441]
  7. Sigrid Juselius Foundation
  8. Academy of Finland [288671]
  9. National Institute of Health Research Exeter Clinical Research Facility

向作者/读者索取更多资源

This study found a correlation between enteroviral infection and autoimmune diseases, as well as type 1 diabetes. The study also revealed a link between genetic predisposition and disease stage with enterovirus infection.
Aims/hypothesis Enteroviral infection has been implicated consistently as a key environmental factor correlating with the appearance of autoimmunity and/or the presence of overt type 1 diabetes, in which pancreatic insulin-producing beta cells are destroyed by an autoimmune response. Genetic predisposition through variation in the type 1 diabetes risk gene IFIH1 (interferon induced with helicase C domain 1), which encodes the viral pattern-recognition receptor melanoma differentiation-associated protein 5 (MDA5), supports a potential link between enterovirus infection and type 1 diabetes. Methods We used molecular techniques to detect enterovirus RNA in peripheral blood samples (in separated cellular compartments or plasma) from two cohorts comprising 79 children or 72 adults that include individuals with and without type 1 diabetes who had multiple autoantibodies. We also used immunohistochemistry to detect the enteroviral protein VP1 in the pancreatic islets of post-mortem donors (n=43) with type 1 diabetes. Results We observed enhanced detection sensitivity when sampling the cellular compartment compared with the non-cellular compartment of peripheral blood (OR 21.69; 95% CI 3.64, 229.20; p<0.0001). In addition, we show that children with autoimmunity are more likely to test positive for enterovirus RNA than those without autoimmunity (OR 11.60; 95% CI 1.89, 126.90; p=0.0065). Furthermore, we found that individuals carrying the predisposing allele (946(Thr)) of the common variant in IFIH1 (rs1990760, Thr946Ala) are more likely to test positive for enterovirus in peripheral blood (OR 3.07; 95% CI 1.02, 8.58; p=0.045). In contrast, using immunohistochemistry, there was no correlation between the common variant in IFIH1 and detection of enteroviral VP1 protein in the pancreatic islets of donors with type 1 diabetes. Conclusions/interpretation Our data indicate that, in peripheral blood, antigen-presenting cells are the predominant source of enterovirus infection, and that infection is correlated with disease stage and genetic predisposition, thereby supporting a role for enterovirus infection prior to disease onset.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据