A pathogenetic link between aplastic anemia and paroxysmal nocturnal hemoglobinuria is suggested by a high frequency of aplastic anemia patients with a deficiency of phosphatidylinositol glycan anchored proteins.
A pathogenetic link between aplastic anemia and paroxysmal nocturnal hemoglobinuria is suggested by a high frequency of aplastic anemia patients with a deficiency of phosphatidylinositol glycan anchored proteins.
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发表时间：
1995
影响因子：
2.6
通讯作者：
H. Schrezenmeier;B. Hertenstein;B. Wagner;A. Raghavachar;Hermann Heimpel
中科院分区：
文献类型：
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作者：
H. Schrezenmeier;B. Hertenstein;B. Wagner;A. Raghavachar;Hermann Heimpel
阵发性睡眠性血红蛋白尿症（PNH）和再生障碍性贫血（AA）之间的临床相互关系促进了对发病机制联系的研究。由于PNH的分子缺陷是未能表达磷脂酰肌醇聚糖锚定蛋白（PIG-AP），我们研究了这种缺陷是否也可以在典型AA患者的外周血细胞上证明。通过流式细胞术使用单克隆抗体（MAb）CD 16和CD 66 b（粒细胞）、CD 14和CD 48（单核细胞）、CD 48和CD 52（淋巴细胞）以及CD 55和CD 59（红细胞）对PIG-AP的表达进行定量。我们分析了52例获得性AA患者的细胞。在52名患者中的27名（52%）中至少在一种细胞谱系中鉴定出PIG-AP缺陷群体。27例AA患者中有25例涉及粒细胞，25例中有18例涉及单核细胞，27例中有7例涉及淋巴细胞，27例中有7例涉及红细胞。在至少一种细胞谱系中，无PIG-AP缺陷群体的患者组对标准免疫抑制治疗的应答率显著高于PIG-AP缺陷群体的患者组（85.7%对30.4%; p < 0.0003）。我们的研究结果表明，PIG-AP表达的基础上，AA患者的比例显示的功能，典型的AA沿着与PNH表型是显著高于以前认识到的。PIG-AP表达的模式可能会识别AA患者的亚组，这些亚组在潜在机制以及疾病过程中存在差异。
The clinical interrelationship between paroxysmal nocturnal hemoglobinuria (PNH) and aplastic anemia (AA) promoted a search for a pathogenetic link. Since the molecular defect in PNH is a failure to express phosphatidylinositol glycan-anchored proteins (PIG-AP), we investigated whether this defect could also be demonstrated on peripheral blood cells of patients with typical AA. Quantification of the expression of PIG-AP was performed by flow cytometry using the monoclonal antibodies (MAbs) CD16 and CD66b for granulocytes, CD14 and CD48 for monocytes, CD48 and CD52 for lymphocytes, and CD55 and CD59 for erythrocytes. We analyzed cells from 52 patients with acquired AA. A PIG-AP-defective population was identified in 27 of 52 patients (52%) in at least one cell lineage. Granulocytes were involved in 25 of 27, monocytes in 18 of 25, lymphocytes in seven of 27, and erythrocytes in seven of 27 AA patients who were affected by a PIG-AP deficiency. The response rate to standard immunosuppressive therapy was significantly higher in the group of patients without a PIG-AP-deficient population than in patients with a PIG-AP-deficient population in at least one cell lineage (85.7 vs. 30.4%; p < 0.0003). Our results demonstrate that on the basis of PIG-AP expression, the proportion of AA patients who show features of typical AA along with a PNH phenotype is substantially higher than previously recognized. The pattern of PIG-AP expression might identify subgroups of AA patients who differ in the underlying mechanism as well as in the course of their disease.