Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002874 (aplastic anemia)
 5,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied three glycosylphosphatidylinositol (GPI) linked proteins on the erythrocytes of 14 patients with paroxysmal nocturnal haemoglobinuria (PNH). The pattern observed was bimodal in 12 of the patients and trimodal in two. Ten patients had a red cell population with normal CD59 antigen (membrane inhibitor of reactive lysis, MIRL), decay accelerating factor (DAF or CD55) and lymphocyte function-associated antigen (LFA-3 or CD58) and a second abnormal PNH population with absent CD59 antigen, DAF and LFA-3. The other two patients with a bimodal pattern had a red cell population with normal CD59 antigen, DAF and LFA-3 and an abnormal population with reduced, but not absent, CD59 antigen and DAF. The LFA-3 on the abnormal red cells in these two patients appeared to be only slightly reduced. The two patients with a trimodal pattern had a normal population, a population with reduced, not absent, CD59 antigen and DAF, and a population with complete absence of CD59 antigen, DAF and LFA-3. The accuracy of the Ham test in estimating the proportion of red cells with the PNH defect in the two types of PNH was assessed. The case of one patient who appeared to be 'rescued' from severe aplastic anaemia by the development of PNH is described.
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PMID:Two distinct patterns of glycosylphosphatidylinositol (GPI) linked protein deficiency in the red cells of patients with paroxysmal nocturnal haemoglobinuria. 137 29

Paroxysmal nocturnal haemoglobinuria (PNH) is now generally accepted as a disease in which bone marrow derived cells are deficient in phosphatidylinositolglycan (PIG)-anchored surface molecules. A series of new monoclonal antibodies detecting PIG-anchored surface structures on human leucocytes (CD48, CD55, CD59) has recently been described. In the present study 12 patients with the diagnosis PNH and a positive Ham test were examined for PIG-anchored surface antigen expression on various cell lineages using immunofluorescence. In all patients deficient cells were detected in erythrocyte, granulocyte and monocyte analysis. A deficient lymphocyte subset was also observed in all but one of these patients. Using two-colour analysis, all lymphocyte subpopulations such as T, B and NK cells were found to be affected. In addition, peripheral blood cells of 22 patients with severe aplastic anaemia (SAA) were tested for the PIG-anchoring defect. In five of these patients the defect was detected, and in four of the five the lack of PIG-anchored molecules was confined to the granulocyte and monocyte lineages apparently without affecting the erythrocytes. The results of these studies demonstrate that cytofluorographic testing of peripheral blood cells provides a simple and reliable method for establishing the diagnosis of PNH. Furthermore, especially in the case of aplastic anaemia patients, the sensitivity of immunophenotyping might be superior to conventional laboratory tests.
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PMID:Diagnosis of paroxysmal nocturnal haemoglobinuria using immunophenotyping of peripheral blood cells. 175 77

Paroxysmal nocturnal hemoglobinuria (PNH) is a disease that affects not only red cells, but other blood cells as well. The common defect is supposed to be an acquired deficiency of glycosyl-phosphatidylinositol (GPI)-anchored membrane proteins, which may be present already at the hematopoietic stem cell level. Recently, a panel of monoclonal antibodies (MoAbs) has become available directed against various GPI-linked membrane proteins. This makes it possible to study various cell lineages for the deficiency of such proteins in PNH in more detail. Using cytofluorography, we could show that the granulocytes of 20 different PNH patients miss not only GPI-linked FcRIII (CD16 antigen), but also three other GPI-linked proteins, ie, CD24 antigen, CD67 antigen and a granulocyte-specific 50 to 80 Kd antigen. The affected granulocytes were not only neutrophils but also eosinophils, as was found in a more detailed analysis of three patients. Moreover, in all 10 PNH patients tested, the monocytes were found to be deficient for the GPI-linked CD14 antigen, and we found with CD24 and CD55 (DAF) antibodies that lymphocytes may be involved as well. However, abnormal B and T lymphocytes were detected only in a subset of patients (2 of 10 tested). The uniform deficiency of GPI-linked proteins of granulocytes allows the introduction of a new diagnostic cytofluorometric assay for PNH with MoAbs against GPI-linked granulocytic antigens. This test was positive in all PNH patients studied and not in a group of 40 control patients or 50 normal donors, with the exception of three of 16 aplastic anemia (AA) patients. In the three AA patients, subpopulations (10% to 20%) of PNH granulocytes could be detected, whereas these patients had a negative acidified serum (Ham) test. This indicates that the new test is more sensitive than the Ham test and allows the early diagnosis of PNH in AA. An advantage of the neutrophil assay is that, in contrast to the Ham test, it is not influenced by recent red-cell transfusions. Moreover, it is possible to quantify the number of affected cells by single cell analysis.
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PMID:Deficiency of glycosyl-phosphatidylinositol-linked membrane glycoproteins of leukocytes in paroxysmal nocturnal hemoglobinuria, description of a new diagnostic cytofluorometric assay. 214 90

To evaluate quality of hematologic recovery in aplastic anemia (AA) patients treated with cyclosporine A (CyA), we examined polymorphonuclear leukocytes (PMNCL) from 25 AA patients for clonality and glycosyl-phosphatidylinositol (GPI)-anchored membrane protein expression. Using three different X-linked gene probes, we failed to detect clonal hematopoiesis in seven CyA-responsive female patients. Clonal hematopoiesis was detected in two of six female patients refractory to CyA therapy, although one of these two patients had shown monoclonality before therapy. Flow-cytometric analysis revealed a normal expression of GPI-linked membrane proteins, including CD55, CD59, and CD16 on PMN in all patients treated with CyA, irrespective of response, except for one patient who had a small proportion of GPI-anchored membrane protein-negative cells before therapy. The proportion remained unchanged 41 months after hematologic recovery following CyA therapy. These findings suggest that successful therapy of AA with CyA may not be associated with a significant risk of developing late clonal complications, such as paroxysmal nocturnal hemoglobinuria (PNH) and myelodysplasia.
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PMID:Quality of hematologic recovery in patients with aplastic anemia following cyclosporine therapy. 753 14

Using a flow cytometric analysis, CD55 (decay-accelerating factor), CD59 and CD58 have been measured on neutrophils from 12 aplastic anaemia (AA) patients who were long-term survivors after immunosuppressive therapy (IS), 17 healthy individuals, four patients with PNH, and six patients with other haematological disorders. The neutrophils from normal control patients and the six patients with other haematological disorders showed 98 +/- 2% (mean +/- SD) positive granulocytes for CD55. Corresponding values were low (12%, 26%, 51% and 58%) on the primarily PNH patients. Among the 12 AA patients examined, seven had normal and five low values (59% in two, 70%, 71% and 82%). Among the five AA patients who showed CD55 neutrophil deficiency, four had showed an incomplete response after the initial IS treatment and the other relapsed following an initial haematological complete response; three cases had a positive Ham's test and two were negative. Our data suggest that the development of PNH clones is a frequent finding in AA long-term survivors, mainly in those who had shown an incomplete response following IS. Neutrophil CD55 expression analysis by flow cytometry could be useful to detect clonal evolution in these patients.
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PMID:Flow cytometric analysis of decay-accelerating factor (CD55) on neutrophils from aplastic anaemia patients. 754 52

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)
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PMID:Aplastic anemia and paroxysmal nocturnal hemoglobinuria: search for a pathogenetic link. 785 65

Scleroderma and aplastic anaemia (AA) occurred simultaneously in a patient. Treatment with antilymphocyte globulin (ALG) resulted in some improvement of the scleroderma and a partial, temporary response of the AA. Both the scleroderma and AA then responded dramatically to cyclosporin (CSA) therapy. Subsequently, a positive Ham's test, together with a reduction in the phosphatidyl-inositolglycan (PIG) anchored membrane proteins decay accelerating factor (DAF, CD55) and membrane inhibitor of reactive lysis (MIRL, CD59), confirmed a diagnosis of paroxysmal nocturnal haemoglobinuria (PNH) affecting erythroid, myeloid and lymphoid cell lineages. We hypothesize that the pathogenesis of the bone marrow failure in this patient was a stem cell defect with a secondary immune response involving T-lymphocytes that may have simultaneously triggered the pancytopenia and scleroderma.
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PMID:Response of aplastic anaemia and scleroderma to cyclosporin. 791 56

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.
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PMID: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. 799 74

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired disorder of hematopoiesis in which affected cells are deficient in glycosylphosphatidyl-inositol (GPI) anchored surface proteins. The authors used flow cytometry to study 10 patients with PNH. They used a comprehensive panel of monoclonal antibodies against all nine currently known GPI-linked surface proteins (CD14, CD16, CD24, CD48, CD55, CD58, CD59, CD67, CD73) on cells of various lineages. Deficient cells were identified in the granulocytic-monocytic and erythroid lineages in all patients. However, the lymphoid lineage was affected in only eight patients. The patterns of deficiency were variable, with deficient cells constituting a part to all of the cells in the lineages tested. Certain proteins, including CD16, CD58, and CD59, appeared to be preferentially expressed, despite severe deficiencies of other GPI-linked proteins. Moreover, a trimodal pattern of expression of CD16, CD48, and CD59 was observed, in which a population of cells with intermediate levels of expression were identified in addition to positive and deficient cells. The authors' findings indicated a great degree of heterogeneity in the patterns and levels of expression of the GPI-linked proteins in the various cell types, as well as a possible heterogeneity in lineage involvement. The different patterns of expression of GPI-linked proteins should be considered when using flow cytometry to diagnose PNH. Finally, the clinical progression in some of the patients suggested a possible link between PNH, aplastic anemia, and myelodysplasia.
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PMID:Flow cytometric measurement of glycosylphosphatidyl-inositol-linked surface proteins on blood cells of patients with paroxysmal nocturnal hemoglobinuria. 803 65

Twenty-six consecutive patients with acquired aplastic anaemia (AA) and nine patients with de novo paroxysmal nocturnal haemoglobinuria (PNH) were included in this study. In these 35 patients a GPI-anchored molecule defect at the platelet surface was investigated by flow-cytometry. Platelets from eight out of the nine patients with de novo PNH were found to be deficient for the GPI-anchored molecule CD55, CD58 and CD59. We also detected a GPI-anchored molecule defect on monocytes, granulocytes, and erythrocytes in all patients with de novo PNH. Among the 26 AA patients, a GPI defect was detected on platelets in five patients. Interestingly, these five patients were also found to have a GPI-anchored molecule defect on erythrocytes, whereas in 10 patients the GPI-anchored molecule defect was only detected on monocyte and polymorphonuclear (PMN) cells.
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PMID:Aplastic anaemia and paroxysmal nocturnal haemoglobinuria: a study of the GPI-anchored proteins on human platelets. 865 77


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