Department of Neurology IV, Neuromuscular Diseases and Neuroimmunology, Fondazione Istituto Neurologico Carlo Besta, Milan, Italy.
Ann Neurol. 2010 Jun;67(6):726-38. doi: 10.1002/ana.21902.
Increasing evidence supports a link between Epstein-Barr virus (EBV), a ubiquitous B-lymphotropic human herpesvirus, and common B-cell-related autoimmune diseases. We sought evidence of EBV infection in thymuses from patients with myasthenia gravis (MG), an autoimmune disease characterized by intrathymic B-cell activation.
Seventeen MG thymuses (6 follicular hyperplastic, 6 diffuse hyperplastic, 5 involuted) and 6 control thymuses were analyzed using in situ hybridization for EBV-encoded small RNAs (EBERs), immunohistochemistry for EBV latent and lytic proteins, and polymerase chain reaction for EBV DNA and mRNA.
All 17 MG thymuses showed evidence of active EBV infection, whereas none of the control thymuses were infected. Cells expressing EBERs (12 of 17) and EBV latency proteins (EBNA2, LMP1, and LMP2A) (16 of 17) were detected in medullary infiltrates and in germinal centers. Cells expressing early (BFRF1, BMRF1) and late (p160, gp350/220) lytic phase EBV proteins were present in 16 MG thymuses. Latency (EBNA1, LMP2A) or lytic (BZLF1) transcripts (often both) were present in all MG thymuses, and EBV DNA (LMP1 gene) was detected in 13 MG thymuses. We also found CD8+ T cells, CD56 + CD3-natural killer cells, and BDCA-2+ plasmacytoid dendritic cells in immune infiltrates of MG thymuses, but not germinal centers, suggesting an attempt of the immune system to counteract EBV infection.
Dysregulated EBV infection in the pathological thymus appears common in MG and may contribute to the immunological alterations initiating and/or perpetuating the disease.
越来越多的证据表明，人类疱疹病毒 4 型（EBV）与常见的 B 细胞相关自身免疫性疾病之间存在关联。EBV 是一种普遍存在的 B 淋巴细胞嗜性人类疱疹病毒。我们试图在重症肌无力（MG）患者的胸腺中找到 EBV 感染的证据，MG 是一种以胸内 B 细胞激活为特征的自身免疫性疾病。
使用原位杂交法检测 EBV 编码的小 RNA（EBERs）、免疫组织化学法检测 EBV 潜伏和裂解蛋白，以及聚合酶链反应法检测 EBV DNA 和 mRNA，对 17 例 MG 胸腺（6 例滤泡性增生、6 例弥漫性增生、5 例萎缩）和 6 例对照胸腺进行分析。
17 例 MG 胸腺均显示出活跃的 EBV 感染证据，而对照组无感染。在髓质浸润和生发中心检测到表达 EBERs（17 例中的 12 例）和 EBV 潜伏蛋白（EBNA2、LMP1 和 LMP2A）（17 例中的 16 例）的细胞。在 16 例 MG 胸腺中存在表达早期（BFRF1、BMRF1）和晚期（p160、gp350/220）裂解相 EBV 蛋白的细胞。在所有 MG 胸腺中均存在潜伏（EBNA1、LMP2A）或裂解（BZLF1）转录本（通常两者均有），在 13 例 MG 胸腺中检测到 EBV DNA（LMP1 基因）。我们还发现 CD8+T 细胞、CD56+CD3-自然杀伤细胞和 BDCA-2+浆细胞样树突状细胞浸润在 MG 胸腺的免疫浸润中，但不在生发中心，这表明免疫系统试图对抗 EBV 感染。
病理性胸腺中失调的 EBV 感染在 MG 中似乎很常见，可能导致启动和/或持续疾病的免疫改变。
