Siebert J D, Ambinder R F, Napoli V M, Quintanilla-Martinez L, Banks P M, Gulley M L
Department of Pathology, University of Texas Health Science Center, San Antonio 78284-7750, USA.
Hum Pathol. 1995 Nov;26(11):1191-5. doi: 10.1016/0046-8177(95)90192-2.
Severe immunodeficiency is associated with reactivation of latent Epstein-Barr virus (EBV) that is manifested by virus replication. It is unknown whether EBV replication also occurs in the Hodgkin's disease (HD) tissue of patients infected with the human immunodeficiency virus (HIV). Therefore, we studied paraffin-embedded lymph nodes from 13 cases of HIV-associated HD to determine the latent or replicative state of EBV infection. All patients were seropositive HIV-infected men; additional clinical information was available for 12 patients. The risk factor(s) for HIV infection were homosexuality (n = 7), intravenous drug abuse (n = 2), homosexuality and intravenous drug abuse (n = 1), sexual promiscuity (n = 1), or hemophilia (n = 1). Advanced clinical stage and B symptoms were common at the time of initial diagnosis of HD. The histological subtype of Hodgkin's disease was universally mixed cellularity, except for a single case classified as nodular sclerosis. Seven cases exhibited foci of relative lymphoid depletion. Five cases contained foci of necrosis. Reed-Sternberg (RS) cells and RS cell variants were positive for CD30/BerH2 and negative for CD45/LCA, CD45RO/UCHL1, and CD20/L26 in all cases. Tumor cells were positive for CD15/LeuM1 in seven cases. In all 13 cases, RS cells and RS cell variants were infected by latent EBV as shown by in situ hybridization to EBV-encoded ribonucleic acid (EBER1). In 12 of 13 cases neoplastic cells coexpressed EBV latent membrane protein 1 (LMP1). EBV replication was examined by two different methods: immunohistochemistry to identify EBV-encoded BZLF1 protein and in situ hybridization to detect EBV BHLF1 transcripts. No positivity in RS or RS cell variants was detected with either assay of EBV replication (95% confidence interval [CI] = 0% to 23%). The findings confirm that EBV is detected more frequently in HIV-associated HD when compared with immunocompetent patients with HD. The findings also suggest that EBV is tightly latent within RS and RS cell variants of HIV-associated HD. It appears that factors other than host immune status are important in maintaining EBV latency in HIV-associated HD.
严重免疫缺陷与潜伏性EB病毒（EBV）再激活相关，表现为病毒复制。目前尚不清楚在感染人类免疫缺陷病毒（HIV）的患者的霍奇金淋巴瘤（HD）组织中是否也会发生EBV复制。因此，我们研究了13例HIV相关HD患者的石蜡包埋淋巴结，以确定EBV感染的潜伏或复制状态。所有患者均为HIV血清阳性男性；12例患者有额外的临床信息。HIV感染的危险因素包括同性恋（7例）、静脉吸毒（2例）、同性恋和静脉吸毒（1例）、性乱交（1例）或血友病（1例）。HD初诊时，晚期临床分期和B症状较为常见。除1例分类为结节硬化型外，霍奇金淋巴瘤的组织学亚型均为混合细胞型。7例出现相对淋巴细胞耗竭灶。5例有坏死灶。所有病例中，里德-斯腾伯格（RS）细胞和RS细胞变异体CD30/BerH2呈阳性，而CD45/LCA、CD45RO/UCHL1和CD20/L26呈阴性。7例肿瘤细胞CD15/LeuM1呈阳性。原位杂交检测EB病毒编码的核糖核酸（EBER1）显示，所有13例病例中RS细胞和RS细胞变异体均被潜伏性EBV感染。13例中有12例肿瘤细胞共表达EB病毒潜伏膜蛋白1（LMP1）。通过两种不同方法检测EBV复制：免疫组化鉴定EB病毒编码的BZLF1蛋白，原位杂交检测EBV BHLF1转录本。两种EBV复制检测方法在RS细胞或RS细胞变异体中均未检测到阳性结果（95%置信区间[CI]=0%至23%）。这些发现证实，与免疫功能正常的HD患者相比，HIV相关HD中EBV的检出频率更高。这些发现还表明，EBV在HIV相关HD的RS细胞和RS细胞变异体中处于紧密潜伏状态。看来，除宿主免疫状态外，其他因素在维持HIV相关HD中EBV潜伏方面也很重要。
