Hertenstein B, Wagner B, Bunjes D, Duncker C, Raghavachar A, Arnold R, Heimpel H, Schrezenmeier H
Department of Internal Medicine III, University of Ulm, Germany.
Blood. 1995 Aug 15;86(4):1487-92.
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.
CD52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、单核细胞以及大多数B细胞非霍奇金淋巴瘤中表达。我们观察到3例难治性B细胞淋巴瘤患者在静脉注射人源化抗CD52单克隆抗体Campath-1H后出现了CD52阴性T细胞，并能够确定其潜在机制。除了缺乏CD52外，2例患者的CD52阴性T细胞上未检测到PIG-AP CD48和CD59。建立了来自这2例患者的PIG-AP缺陷T细胞克隆。对PIG-A基因mRNA的分析显示，其中1例患者的T细胞克隆中mRNA大小异常，提示PIG-A基因突变是PIG-AP表达缺陷的原因。阵发性夜间血红蛋白尿（PNH）和再生障碍性贫血中PIG-AP缺陷细胞的出现被认为是由于针对PIG-AP阳性造血的免疫攻击逃逸所致。我们的结果支持这样一种假说，即针对PIG-AP CD52的攻击可能导致具有PNH细胞表型和分子特征的PIG锚定缺陷细胞群体的扩增。
