Detection of poliovirus-infected macrophages in thymus of patients with myasthenia gravis
Detection of poliovirus-infected macrophages in thymus of patients with myasthenia gravis
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DOI：
10.1212/wnl.0b013e3181d7d884
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发表时间：
2010-04-06
期刊：
影响因子：
9.9
通讯作者：
Bernasconi, P.
中科院分区：
文献类型：
--
作者：
Cavalcante, P.;Barberis, M.;Bernasconi, P.
背景：遗传和环境因素被认为是自身免疫性疾病重症肌无力（MG）的病因。长期以来，人们一直怀疑病毒参与其中，但尚未发现直接证据。我们最近报道toll样受体4 (TLR4)-先天免疫的关键激活因子-在一些MG患者的胸腺中过度表达，提示病原体感染胸腺可能参与MG的发病机制。我们寻找MG患者胸腺内感染的证据。方法：采用PCR技术对27例MG胸腺（累及性胸腺6例，增生性胸腺7例，胸腺炎5例，胸腺瘤9例）、18例非病理对照胸腺和10例非病理对照胸腺（胸腺瘤8例，增生性胸腺2例）进行巨细胞病毒、水痘带状疱疹病毒、单纯疱疹病毒1型和2型、真细菌、呼吸道合胞病毒和肠病毒的检测。采用免疫组织化学和双免疫荧光技术检测胸腺标本肠病毒衣壳蛋白VP1，分析VP1阳性细胞中TLR4的表达。结果：MG胸腺中检出脊髓灰质炎病毒4例（14.8%），胸腺炎2例，胸腺瘤2例。在任何对照胸腺中均未检测到病毒。在所有4个胸腺中观察到正链和负链脊髓灰质炎病毒RNA水平呈线性相关，提示胸腺持续感染。在所有pv阳性胸腺中，分布于胸腺髓质的cd68阳性巨噬细胞细胞质中均检测到VP1蛋白。VP1和TLR4在感染细胞中共定位。结论：脊髓灰质炎病毒感染的巨噬细胞存在于一些重症肌无力患者的胸腺中，提示病毒在导致该疾病的胸腺内改变中起作用。神经病学(R) 2010；74:1118 - 1126
Background: Genetic and environmental factors are thought to contribute to the etiology of the autoimmune disease myasthenia gravis (MG). Viral involvement has long been suspected, but direct evidence of involvement has not been found. We recently reported that Toll-like receptor 4 (TLR4)-a key activator of innate immunity-was overexpressed in the thymus of some patients with MG, suggesting that thymic infection by pathogens might be involved in MG pathogenesis. We searched for evidence of intrathymic infection in patients with MG.Methods: Twenty-seven MG thymuses (6 involuted, 7 hyperplastic, 5 thymitis, and 9 thymoma) previously tested for TLR4 expression, 18 nonpathologic control thymuses, and 10 pathologic control thymuses from patients without MG (8 thymoma and 2 hyperplastic) were analyzed for cytomegalovirus, varicella-zoster virus, herpes simplex virus types 1 and 2, eubacteria, respiratory syncytial virus, and enteroviruses using PCR techniques. Immunohistochemistry and double immunofluorescence were used to detect enterovirus capsid protein VP1 in thymic specimens and analyze TLR4 expression in VP1-positive cells.Results: Poliovirus was detected in 4 MG thymuses (14.8%; 2 thymitis and 2 thymoma). No virus was detected in any control thymus. A linear correlation between plus and minus strand poliovirus RNA levels was observed in all 4 thymuses, suggesting persistent thymic infection. VP1 protein was detected in the cytoplasm of CD68-positive macrophages scattered through thymic medulla in all PV-positive thymuses. VP1 and TLR4 colocalized in infected cells.Conclusions: Poliovirus-infected macrophages are present in thymus of some patients with myasthenia gravis, suggesting a viral contribution to the intrathymic alterations leading to the disease. Neurology (R) 2010;74:1118-1126