The Center for Infectious Medicine, Department of Medicine HS, Karolinska Institutet, Karolinska University Hospital Huddinge F59, SE-141 86 Stockholm, Sweden.
Diabetologia. 2013 Apr;56(4):867-74. doi: 10.1007/s00125-013-2834-z. Epub 2013 Jan 24.
AIMS/HYPOTHESIS: Enterovirus (e.g. Coxsackie B virus serotypes [CVBs]) infections may be associated with development of type 1 diabetes. Studies conducted in several European countries have, however, shown an inverse correlation between the incidence of type 1 diabetes and the prevalence of enterovirus infections. These findings could in part be explained by an extension of the poliovirus hypothesis, suggesting that the absence of maternally transferred antibodies protecting offspring from early infection increases the risk for diabetes development. Experimental evidence supporting this hypothesis in type 1 diabetes is, however, lacking. As maternally transferred protection from infection is a crucial component of the extended poliovirus hypothesis, we here tested the hypothesis that previously infected females transfer protection against infection and diabetes to offspring.
The induction of CVB-specific maternal antibodies and transfer of protection from virus infection, replication and development of virus-induced diabetes to offspring was assessed using NOD and Socs1-transgenic NOD mice.
Infected mice produced neutralising antibodies to CVB. Offspring from infected females were positive for neutralising antibodies and were strongly protected from both infection and experimental diabetes.
CONCLUSIONS/INTERPRETATION: Our study shows that maternally transferred antibodies protect offspring from enterovirus infection and virus-induced diabetes. This suggests that the absence of maternally provided protection increases the risk for severe outcomes after an enterovirus infection in offspring. Moreover, our findings may have implications for the design of prospective studies aimed at investigating the possible role of enterovirus infections in the aetiology of human type 1 diabetes.
目的/假设：肠病毒（例如柯萨奇 B 病毒血清型[CVBs]）感染可能与 1 型糖尿病的发生有关。然而，在几个欧洲国家进行的研究表明，1 型糖尿病的发病率与肠病毒感染的流行之间呈反比关系。这些发现部分可以用脊髓灰质炎病毒假说的扩展来解释，该假说表明，缺乏母体转移抗体来保护后代免受早期感染会增加糖尿病发生的风险。然而，缺乏支持 1 型糖尿病这一假说的实验证据。由于感染的母体保护是扩展的脊髓灰质炎病毒假说的关键组成部分，我们在此测试了先前感染的女性是否将针对感染和糖尿病的保护传递给后代的假设。
使用 NOD 和 Socs1 转基因 NOD 小鼠评估 CVB 特异性母体抗体的诱导以及从病毒感染、复制和发展到病毒诱导的糖尿病的保护作用向后代的转移。
感染的小鼠产生了针对 CVB 的中和抗体。来自感染母亲的后代对中和抗体呈阳性，并且受到强烈的保护，免受感染和实验性糖尿病的影响。
结论/解释：我们的研究表明，母体转移的抗体可保护后代免受肠病毒感染和病毒诱导的糖尿病。这表明，缺乏母体提供的保护会增加后代在肠病毒感染后发生严重后果的风险。此外，我们的发现可能对旨在调查肠病毒感染在人类 1 型糖尿病发病机制中可能作用的前瞻性研究的设计具有重要意义。
