Exacerbated pathology of viral encephalitis in mice with central nervous system-specific autoantibodies.
Exacerbated pathology of viral encephalitis in mice with central nervous system-specific autoantibodies.
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DOI：
10.2353/ajpath.2007.060893
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发表时间：
2007-02
期刊：
影响因子：
--
通讯作者：
von Herrath MG
中科院分区：
文献类型：
--
作者：
Burrer R;Buchmeier MJ;Wolfe T;Ting JP;Feuer R;Iglesias A;von Herrath MG
我们在这里检查了具有中枢神经系统 (CNS) 特异性抗原髓磷脂少突胶质细胞糖蛋白自身抗体的小鼠中病毒性脑脊髓炎 [小鼠肝炎病毒 (MHV) A59、泰勒脑脊髓炎病毒和柯萨奇病毒 B3] 的结果，这些抗体通常不会发展为临床疾病。所有三种病毒感染中均存在自身抗体，从而增加了急性病毒性中枢神经系统疾病的发病率和死亡率。感染 MHV 时转移含有自身抗体的血清足以重现病情恶化。研究发现自身抗体的存在会导致单核细胞向大脑的浸润增加。具有中枢神经系统特异性自身抗体的 MHV 感染小鼠的大脑和脊髓的早期脱髓鞘严重加剧。抗体介导的恶化被证明不依赖于补体系统，但需要 Fc 受体的表达，因为它在 C'-3 缺陷的小鼠中观察到，但在 Fc 受体缺陷的小鼠中没有观察到。我们的研究表明，在存在其他潜在自身免疫性疾病的情况下，感染可能会导致更深刻的免疫病理学变化。
We examine here the outcome of viral encephalomyelitis [mouse hepatitis virus (MHV) A59, Theiler’s encephalomyelitis virus, and Coxsackievirus B3] in mice with autoantibodies to a central nervous system (CNS)-specific antigen, myelin oligodendrocyte glycoprotein, that usually develop no clinical disease. Morbidity and mortality of the acute viral CNS disease was augmented by the presence of the autoantibodies in all three viral infections. Transfer of serum containing the autoantibodies at the time of infection with MHV was sufficient to reproduce the exacerbated disease. The presence of the autoantibodies was found to result in increased infiltration of mononuclear cells into the brain. Early demyelination was severely augmented in brains and spinal cords of MHV-infected mice with CNS-specific autoantibodies. The antibody-mediated exacerbation was shown to be independent of the complement system but to require expression of Fc receptors, because it was observed in C′-3-deficient but not in Fc receptor-deficient mice. Our study illustrates the possibility that infections can lead to much more profound immunopathology in the presence of an otherwise latent autoimmune condition.
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