Epstein-Barr virus-associated B-cell proliferations of diverse clonal origins after bone marrow transplantation in a 12-year-old patient with severe combined immunodeficiency.
Epstein-Barr virus-associated B-cell proliferations of diverse clonal origins after bone marrow transplantation in a 12-year-old patient with severe combined immunodeficiency.
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一名 12 岁严重联合免疫缺陷患者骨髓移植后，不同克隆来源的 Epstein-Barr 病毒相关 B 细胞增殖。
DOI：
10.1056/nejm198505023121804
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
Grumet,FC
中科院分区：
文献类型：
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作者：
Shearer,WT;Ritz,J;Finegold,MJ;Guerra,IC;Rosenblatt,HM;Lewis,DE;Pollack,MS;Taber,LH;Sumaya,CV;Grumet,FC
一名患有严重联合免疫缺陷的 12 岁男孩从出生起就一直生活在限菌环境中，他接受了来自组织不相容的兄弟姐妹的骨髓，试图重建免疫功能。为了预防移植物抗宿主病，用单克隆抗体和补体在体外处理供体的骨髓以去除同种异体反应性 T 细胞。移植后80天，患者出现全身性疾病，表现为发热、血小板减少、胃肠道疼痛和出血；他于移植后第 124 天去世。尸检显示，许多器官中存在多种肿瘤样 B 细胞增殖，源自受体。从患者咽部分泌物中分离出EB病毒（EBV）；在自发转化的外周血淋巴细胞、腹膜液炎症细胞和骨髓细胞中发现了 EBV 核抗原；在所有肿瘤组织中都发现了 EBV 基因组。捐赠者的血清显示出过去感染过 EBV 的证据。对肿瘤细胞免疫球蛋白和免疫球蛋白基因 DNA 的分析表明存在单克隆和寡克隆 B 细胞增殖。这些发现为 EBV 诱导的 B 细胞多克隆激活进化为寡克隆 B 细胞增殖并最终进化为单克隆 B 细胞淋巴瘤提供了证据。 （新英格兰医学杂志 1985 年；312：1151-9。）
A 12-year-old boy with severe combined immunodeficiency who had been kept in a gnotobiotic environment since birth received bone marrow from a histoincompatible sibling in an attempt to reconstitute immunologic function. To prevent graft versus host disease, the donor's marrow was treated in vitro with monoclonal antibody and complement to remove alloreactive T cells. Eighty days after transplantation, the patient had a systemic illness characterized by fever, thrombocytopenia, gastrointestinal pain, and bleeding; he died on the 124th post-transplantation day. Postmortem examination revealed multiple tumor-like B-cell proliferations, recipient in origin, in numerous organs. Epstein-Barr virus (EBV) was isolated from the patient's pharyngeal secretions; EBV nuclear antigen was found in spontaneously transformed peripheral-blood lymphocytes, inflammatory cells from peritoneal fluid, and bone marrow cells; and EBV genomes were discovered in all tumor tissues. The donor's serum showed evidence of past EBV infection. Analysis of cellular immunoglobulin and immunoglobulin gene DNA from the tumors indicated both monoclonal and oligoclonal B-cell proliferations.These findings provide evidence for the evolution of EBV-induced polyclonal activation of B cells to oligoclonal B-cell proliferation and finally to monoclonal B-cell lymphoma. (N Engl J Med 1985; 312:1151–9.)