Cavalcante Paola, Maggi Lorenzo, Colleoni Lara, Caldara Rosa, Motta Teresio, Giardina Carmelo, Antozzi Carlo, Berrih-Aknin Sonia, Bernasconi Pia, Mantegazza Renato
Department of Neurology IV, Neuromuscular Diseases and Neuroimmunology, Neurological Institute C. Besta Foundation, 20133 Milan, Italy.
Autoimmune Dis. 2011;2011:213092. doi: 10.4061/2011/213092. Epub 2011 Sep 26.
The thymus plays a major role in myasthenia gravis (MG). Our recent finding of a persistent Epstein-Barr (EBV) virus infection in some MG thymuses, combined with data showing that the thymus is in a proinflammatory state in most patients, supports a viral contribution to the pathogenesis of MG. Aim of this study was to gain further evidence for intrathymic chronic inflammation and EBV infection in MG patients. Transcriptional profiling by low density array and real-time PCR showed overexpression of genes involved in inflammatory and immune response in MG thymuses. Real-time PCR for EBV genome, latent (EBER1, EBNA1, LMP1) and lytic (BZLF1) transcripts, and immunohistochemistry for LMP1 and BZLF1 proteins confirmed an active intrathymic EBV infection, further supporting the hypothesis that EBV might contribute to onset or perpetuation of the autoimmune response in MG. Altogether, our results support a role of inflammation and EBV infection as pathogenic features of MG thymus.
胸腺在重症肌无力(MG)中起主要作用。我们最近发现一些MG患者的胸腺中存在持续性EB病毒(EBV)感染,同时有数据表明大多数患者的胸腺处于促炎状态,这支持病毒在MG发病机制中起作用。本研究的目的是进一步获取MG患者胸腺内慢性炎症和EBV感染的证据。通过低密度阵列和实时PCR进行转录谱分析显示,MG胸腺中参与炎症和免疫反应的基因过表达。对EBV基因组、潜伏(EBER1、EBNA1、LMP1)和裂解(BZLF1)转录本进行实时PCR,以及对LMP1和BZLF1蛋白进行免疫组织化学检测,证实胸腺内存在活跃的EBV感染,进一步支持了EBV可能促成MG自身免疫反应的发生或持续的假说。总之,我们的结果支持炎症和EBV感染作为MG胸腺致病特征的作用。