Griscelli-Bennaceur A, Gluckman E, Scrobohaci M L, Jonveaux P, Vu T, Bazarbachi A, Carosella E D, Sigaux F, Socié G
Laboratoire Central d'Hematologie, Hôpital Saint-Louis, Paris, France.
Blood. 1995 Mar 1;85(5):1354-63.
The association of paroxysmal nocturnal hemoglobinuria (PNH) and aplastic anemia (AA) raises the yet unresolved questions as to whether these two disorders are different forms of the same disease. We compared two groups of patients with respect to cytogenetic features, glycosylphosphatidylinositol (GPI)-linked protein expression, protein C/protein S/thrombomodulin/antithrombin III activity, and PIG-A gene expression. The first group consisted of eight patients with PNH (defined as positive Ham and sucrose tests at diagnosis), and the second, 37 patients with AA. Twelve patients with AA later developed a PNH clone. Monoclonal antibodies used to study GPI-linked protein expression (CD14 [on monocytes], CD16 [on neutrophils], CD48 [on lymphocytes and monocytes], CD67 [on neutrophils and eosinophils], and, more recently, CD55, CD58, and CD59 [on erythrocytes]) were also tested on a cohort of 20 normal subjects and five patients with constitutional AA. Ham and sucrose tests were performed on the same day as flow-cytometric analysis. Six of 12 patients with AA, who secondarily developed a PNH clone, had clinical symptoms, while all eight patients with PNH had pancytopenia and/or thrombosis and/or hemolytic anemia. Cytogenetic features were normal in all but two patients. Proteins C and S, thrombomodulin, and antithrombin III levels were within the normal range in patients with PNH and in those with AA (with or without a PNH clone). In patients with PNH, CD16 and CD67 expression were deficient in 78% to 98% of the cells and CD14 in 76% to 100%. By comparison, a GPI-linked defect was detected in 13 patients with AA, affecting a mean of 32% and 33% of CD16/CD67 and CD14 cell populations, respectively. Two of three tested patients with PNH and 1 of 12 patients with AA had a defect in the CD48 lymphocyte population. In a follow-up study of our patient cohort, we used the GPI-linked molecules on granulocytes and monocytes investigated earlier and added the study of CD55, CD58, and CD59 on erythrocytes. Two patients with PNH and 14 with AA were studied for 6 to 13 months after the initial study. Among patients with AA, four in whom no GPI-anchoring defect was detected in the first study had no defect in follow-up studies of all blood-cell subsets (including erythrocytes). Analysis of granulocytes, monocytes, and erythrocytes was performed in 7 of 13 AA patients in whom affected monocytes and granulocytes were previously detected. A GPI-anchoring defect was detected on erythrocytes in five of six.(ABSTRACT TRUNCATED AT 400 WORDS)
阵发性睡眠性血红蛋白尿（PNH）与再生障碍性贫血（AA）的关联引发了尚未解决的问题，即这两种疾病是否为同一疾病的不同形式。我们比较了两组患者的细胞遗传学特征、糖基磷脂酰肌醇（GPI）连接蛋白表达、蛋白C/蛋白S/血栓调节蛋白/抗凝血酶III活性以及PIG-A基因表达。第一组由8例PNH患者组成（诊断时Ham试验和蔗糖试验为阳性），第二组由37例AA患者组成。12例AA患者后来出现了PNH克隆。用于研究GPI连接蛋白表达的单克隆抗体（单核细胞上的CD14、中性粒细胞上的CD16、淋巴细胞和单核细胞上的CD48、中性粒细胞和嗜酸性粒细胞上的CD67，以及最近红细胞上的CD55、CD58和CD59）也在20名正常受试者和5例先天性AA患者的队列中进行了检测。Ham试验和蔗糖试验与流式细胞术分析在同一天进行。继发出现PNH克隆那12例AA患者中有6例有临床症状，而所有8例PNH患者均有全血细胞减少和/或血栓形成和/或溶血性贫血。除2例患者外，所有患者的细胞遗传学特征均正常。PNH患者和AA患者（有或无PNH克隆）的蛋白C和S、血栓调节蛋白以及抗凝血酶III水平均在正常范围内。在PNH患者中，78%至98%的细胞CD16和CD67表达缺陷，76%至100%的细胞CD14表达缺陷。相比之下，在13例AA患者中检测到GPI连接缺陷，分别影响平均32%和33%的CD16/CD67和CD14细胞群体。3例接受检测的PNH患者中有2例以及12例AA患者中有1例CD48淋巴细胞群体存在缺陷。在对我们患者队列的随访研究中，我们使用了之前研究过的粒细胞和单核细胞上的GPI连接分子，并增加了对红细胞上CD55、CD58和CD59的研究。在初始研究后，对2例PNH患者和14例AA患者进行了6至13个月的研究。在AA患者中，最初研究未检测到GPI锚定缺陷的4例患者在所有血细胞亚群（包括红细胞）的随访研究中也无缺陷。在之前检测到受影响单核细胞和粒细胞的13例AA患者中的7例中，对粒细胞、单核细胞和红细胞进行了分析。6例中有5例在红细胞上检测到GPI锚定缺陷。（摘要截断于400字）
