Hanto D W, Frizzera G, Purtilo D T, Sakamoto K, Sullivan J L, Saemundsen A K, Klein G, Simmons R L, Najarian J S
Cancer Res. 1981 Nov;41(11 Pt 1):4253-61.
Six renal transplant recipients with abnormal lymphoproliferative disorders were studied in an attempt to define their clinical features and the role of Epstein-Barr virus (EBV) in their pathogenesis. Patients were either teenage (three) or in the sixth decade (three). The younger patients presented an average of 3 months after transplantation with fever, sore throat, and lymphadenopathy; had been markedly immunosuppressed; frequently had preceding or concomitant cytomegalovirus infections; and two of three had a rapidly fatal course. The older patients presented an average of 5 years after transplantation while on maintenance immunosuppressive drugs; in two of three cases with an oropharyngeal tumor; and had a more indolent, but frequently fatal, clinical course. The most frequent sites of biopsy-proven involvement in these patients were lymph nodes (three), the oropharynx (three), liver (three), bone marrow (three), transplanted kidney (three), colon (two), and central nervous system (two). EBV-specific antibody titers including anti-viral capsid antigen IgG, anti-viral capsid antigen IgM, anti-early antigen, and anti-Epstein-Barr nuclear antigen were serially measured in all patients. Four patients demonstrated serological evidence of a primary (one) or reactivation (three) EBV infection. No patient had significant changes in anti-early antigen or anti-Epstein-Barr nuclear antigen titers. All three patients tested for oropharyngeal shedding of EBV were positive. A touch imprint of one tumor was stained for the presence of Epstein-Barr nuclear antigen, and a majority of cells were positive. EBV complementary RNA/DNA filter hybridization and/or viral DNA/DNA reassociation analysis performed on tumor biopsy specimens in five patients demonstrated multiple EBV genome equivalents per cell in all eight specimens tested. Clinical, pathological, serological, and molecular hybridization studies provide substantial evidence that EBV was the cause of these lymphoproliferative disorders occurring after renal transplantation. Impaired host defenses allow the EBV-transformed B-lymphocytes to escape normal control mechanisms. This impairment is invariable and influenced by many factors resulting in the observed spectrum of disease. Cytogenetic changes, however, may also be important.
对6例患有异常淋巴增生性疾病的肾移植受者进行了研究，以确定其临床特征以及爱泼斯坦-巴尔病毒（EBV）在其发病机制中的作用。患者年龄分别为青少年（3例）或60多岁（3例）。较年轻的患者在移植后平均3个月出现发热、咽痛和淋巴结病；免疫抑制明显；经常有先前或同时存在的巨细胞病毒感染；3例中有2例病程迅速致命。年龄较大的患者在移植后平均5年，当时正在接受维持性免疫抑制药物治疗；3例中有2例患有口咽肿瘤；临床病程较为隐匿，但通常致命。这些患者经活检证实受累最常见的部位是淋巴结（3例）、口咽（3例）、肝脏（3例）、骨髓（3例）、移植肾（3例）、结肠（2例）和中枢神经系统（2例）。对所有患者连续检测了EBV特异性抗体滴度，包括抗病毒衣壳抗原IgG、抗病毒衣壳抗原IgM、抗早期抗原和抗爱泼斯坦-巴尔核抗原。4例患者表现出原发性（1例）或再激活（3例）EBV感染的血清学证据。没有患者的抗早期抗原或抗爱泼斯坦-巴尔核抗原滴度有显著变化。对3例患者进行的口咽EBV脱落检测均为阳性。对一个肿瘤的触片进行爱泼斯坦-巴尔核抗原染色，大多数细胞呈阳性。对5例患者的肿瘤活检标本进行的EBV互补RNA/DNA滤膜杂交和/或病毒DNA/DNA重结合分析显示，在所有8个检测标本中，每个细胞都有多个EBV基因组当量。临床、病理、血清学和分子杂交研究提供了大量证据，表明EBV是这些肾移植后发生的淋巴增生性疾病的病因。宿主防御功能受损使EBV转化的B淋巴细胞逃避正常的控制机制。这种损害是恒定的，并且受许多因素影响，导致观察到的疾病谱。然而，细胞遗传学变化可能也很重要。
