Incomplete immune response to coxsackie B viruses associates with early autoimmunity against insulin
Incomplete immune response to coxsackie B viruses associates with early autoimmunity against insulin
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DOI：
10.1038/srep32899
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发表时间：
2016-09-08
影响因子：
4.6
通讯作者：
Bonifacio, Ezio
中科院分区：
文献类型：
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作者：
Ashton, Michelle P.;Eugster, Anne;Bonifacio, Ezio
病毒感染与1型糖尿病的自身免疫相关。在这里，我们问这种关联是否可以解释的变化，在主机的免疫反应的一个假定的1型致病因素，即科萨基B病毒（CVB）。观察到针对CVB衣壳蛋白的异质性抗体应答。异源性在很大程度上通过与VP 1或VP 2的不同结合来定义。抗VP 2胜任但抗VP 1缺陷的抗体应答不能中和CVB，并且是发展早期胰岛素靶向自身免疫的儿童的特征，表明在幼儿期清除CVB的能力受损。相比之下，患有GAD靶向自身免疫的儿童对CVB有强烈的VP 1和VP 2抗体应答。我们进一步发现，20%的对GAD 65（247-266）肽应答的记忆性CD 4（+）T细胞与对CVB 4 p2C（30-51）肽应答的T细胞共享相同的T细胞受体，从而为分子模拟作为GAD自身免疫机制的潜力提供了直接证据。在这里，我们强调功能性免疫反应之间的差异儿童谁开发胰岛素靶向和GAD靶向自身免疫，并建议儿童谁失去B细胞耐受胰岛素在生命的第一年有一个矛盾的能力受损，安装科萨基病毒的体液免疫反应。
Viral infections are associated with autoimmunity in type 1 diabetes. Here, we asked whether this association could be explained by variations in host immune response to a putative type 1 etiological factor, namely coxsackie B viruses (CVB). Heterogeneous antibody responses were observed against CVB capsid proteins. Heterogeneity was largely defined by different binding to VP1 or VP2. Antibody responses that were anti-VP2 competent but anti-VP1 deficient were unable to neutralize CVB, and were characteristic of children who developed early insulin-targeting autoimmunity, suggesting an impaired ability to clear CVB in early childhood. In contrast, children who developed a GAD-targeting autoimmunity had robust VP1 and VP2 antibody responses to CVB. We further found that 20% of memory CD4(+) T cells responding to the GAD65(247-266) peptide share identical T cell receptors to T cells responding to the CVB4 p2C(30-51) peptide, thereby providing direct evidence for the potential of molecular mimicry as a mechanism for GAD autoimmunity. Here, we highlight functional immune response differences between children who develop insulin-targeting and GAD-targeting autoimmunity, and suggest that children who lose B cell tolerance to insulin within the first years of life have a paradoxical impaired ability to mount humoral immune responses to coxsackie viruses.