The PNH phenotype cells that emerge in most patients after CAMPATH‐1H therapy are present prior to treatment
The PNH phenotype cells that emerge in most patients after CAMPATH‐1H therapy are present prior to treatment
复制标题
大多数患者在 CAMPATH-1H 治疗后出现的 PNH 表型细胞在治疗前就已存在
作者：
C. A.;Raws Tron;J. S.;R. Inson;S.;Richards;A.;English;J. G;Morgan;G.;Hale
由于造血干细胞中 PIG-A 基因的体细胞突变，阵发性睡眠性血红蛋白尿 (PNH) 细胞缺乏糖基磷脂酰肌醇 (GPI) 相关抗原。看来，只有当选择对其有利时，PNH 克隆才能达到可检测的比例。在接受 CAMPATH-1H（一种针对 GPI 连接的 CD52 分子的单克隆抗体）治疗的患者中已鉴定出 GPI 缺陷的 T 淋巴细胞。 CAMPATH-1H 选择缺乏 CD52 的细胞（例如 PNH 样细胞），促进 PNH 样克隆（类似于 PNH）的发育。我们报告称，10/15 的慢性淋巴细胞白血病患者在接受 CAMPATH-1H 治疗后出现了 PNH 样淋巴细胞。其余 5 名患者在任何阶段均未出现 PNH 样细胞，其中一名患者接受了 12 周的治疗。已在一名患者身上发现了失活的 PIG-A 突变。在 CAMPATH-1H 治疗之前，通过对患者的单核细胞进行极其灵敏的基于突变特异性 PCR 的分析，可以检测到这种突变。 CAMPATH-1H 后 GPI 缺陷淋巴细胞的频率和表型以及 CAMPATH-1H 治疗前淋巴细胞中 PIG-A 突变的检测表明，在 CAMPATH-1H 选择对它们有利的细胞之前，此类突变存在于极小比例的细胞中。这表明很大一部分个体的细胞带有流式细胞术无法检测到的 PIG-A 突变，因此可能有发展为 PNH 的潜力。
Paroxysmal nocturnal haemoglobinuria (PNH) cells are deficient in glycosylphosphatidylinositol (GPI) linked antigens due to a somatic mutation of the PIG‐A gene in a haemopoietic stem cell. It appears that a PNH clone reaches detectable proportions only when there is selection in its favour. GPI‐deficient T lymphocytes have been identified in patients treated with CAMPATH‐1H, a monoclonal antibody against the GPI‐linked CD52 molecule. CAMPATH‐1H selects for cells that are deficient in CD52 (such as PNH‐like cells) promoting the development of a PNH‐like clone (analogous to PNH). We report that 10/15 patients with chronic lymphocytic leukaemia developed PNH‐like lymphocytes after therapy with CAMPATH‐1H. The remaining five patients developed no PNH‐like cells at any stage, including one patient who received 12 weeks of therapy. The inactivating PIG‐A mutation has been identified in one patient. This mutation was detectable by an extremely sensitive mutation‐specific PCR‐based analysis in the patient's mononuclear cells prior to CAMPATH‐1H therapy. The frequency and phenotype of GPI‐deficient lymphocytes after CAMPATH‐1H and the detection of a PIG‐A mutation in the lymphocytes prior to CAMPATH‐1H therapy indicated that such mutations were present in a very small proportion of cells prior to selection in their favour by CAMPATH‐1H. This suggests that a large proportion of individuals have cells with PIG‐A mutations that are not detectable by flow cytometry and thus may have the potential to develop PNH.
阵发性睡眠性血红蛋白尿症的分子基础。
影响因子：
2.9
作者：
Yomtovian,R;Prince,GM;Medof,ME
通讯作者：
Medof,ME