Emergence of CD52-, phosphatidylinositolglycan-anchor-deficient T lymphocytes after in vivo application of Campath-1H for refractory B-cell non-Hodgkin lymphoma.
Emergence of CD52-, phosphatidylinositolglycan-anchor-deficient T lymphocytes after in vivo application of Campath-1H for refractory B-cell non-Hodgkin lymphoma.
复制标题
Campath-1H 体内应用治疗难治性 B 细胞非霍奇金淋巴瘤后，CD52-磷脂酰肌醇锚定缺陷 T 淋巴细胞的出现。
作者：
B. Hertenstein;B. Wagner;D. Bunjes;C. Duncker;A. Raghavachar;R. Arnold;Hermann Heimpel;H. Schrezenmeier
CD 52是一种磷脂酰肌醇聚糖（PIG）锚定糖蛋白（PIG-AP），在正常T和B淋巴细胞、单核细胞和大多数B细胞非霍奇金淋巴瘤上表达。我们观察了3例患者静脉注射人源化抗CD 52单克隆抗体Campath-1H治疗难治性B细胞淋巴瘤后CD 52- T细胞的出现，并可以确定其潜在机制。除了不存在CD 52外，在2名患者的CD 52- T细胞上未检测到PIG-AP CD 48和CD 59。建立了来自两名患者的PIG-AP缺陷型T细胞克隆。对PIG-A基因mRNA的分析显示，这些患者中有1例的T细胞克隆大小异常，表明PIG-A基因突变是PIG-AP表达缺陷的原因。逃避针对PIG-AP+造血的免疫攻击已被假设为阵发性睡眠性血红蛋白尿症（PNH）和再生障碍性贫血中PIG-AP缺陷细胞发生的原因。我们的研究结果支持了这一假设，即对PIG-AP CD 52的攻击可能导致PIG锚缺陷细胞群的扩增，其具有PNH细胞的表型和分子特征。
CD52 is a phosphatidylinositolglycan (PIG)-anchored glycoprotein (PIG-AP) expressed on normal T and B lymphocytes, monocytes, and the majority of B-cell non-Hodgkin lymphomas. We observed the emergence of CD52- T cells in 3 patients after intravenous treatment with the humanized anti-CD52 monoclonal antibody Campath-1H for refractory B-cell lymphoma and could identify the underlaying mechanism. In addition to the absence of CD52, the PIG-AP CD48 and CD59 were not detectable on the CD52- T cells in 2 patients. PIG-AP-deficient T-cell clones from both patients were established. Analysis of the mRNA of the PIG-A gene showed an abnormal size in the T-cell clones from 1 of these patients, suggesting that a mutation in the PIG-A gene was the cause of the expression defect of PIG-AP. An escape from an immune attack directed against PIG-AP+ hematopoiesis has been hypothesized as the cause of the occurrence of PIG-AP-deficient cells in paroxysmal nocturnal hemoglobinuria (PNH) and aplastic anemia. Our results support the hypothesis that an attack against the PIG-AP CD52 might lead to the expansion of a PIG-anchor-deficient cell population with the phenotypic and molecular characteristics of PNH cells.
受影响的阵发性睡眠性血红蛋白尿症 T 淋巴细胞在 N-乙酰基-D-葡萄糖胺肌醇磷脂组装方面存在常见缺陷，与 A 类 Thy-1- 鼠淋巴瘤突变体中的缺陷相对应。
DOI：
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发表时间：
1992
期刊：
The Journal of biological chemistry
影响因子：
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作者：
Armstrong,C;Schubert,J;Ueda,E;Knez,JJ;Gelperin,D;Hirose,S;Silber,R;Hollan,S;Schmidt,RE;Medof,ME
通讯作者：
Medof,ME