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 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

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

Paroxystic nocturnal hemoglobinuria (PNH) is an acquired hemolytic anaemia related to an increase susceptibility of erythrocytes to complement-mediated lysis. PNH is a clonal disease of an hematopoietic stem cell which lost, by mutation, the ability to synthesized phospholipid anchor of membranous proteins, i.e. complement regulatory proteins: DAF, C8BP or CD59. The clinical features of PNH are hemoglobinuria episodes associated with chronic hemolytic anaemia or pancytopenia with active bone marrow or aplastic anaemia. The clinical course is marked by severe thrombotic complications (such as Budd-Chiari syndrome), hemorrhages or infections. The diagnosis is confirmed by in vitro hemolysis tests, and now by facs analysis of cell membrane expression of deficient proteins. Different treatments have been proposed with various results (corticosteroid therapy, androgens, chemotherapy...) but the only way to eliminate the abnormal clone appears to be related bone marrow allograft.
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PMID:[Paroxysmal nocturnal hemoglobinuria]. 823 86

Treatment of severe aplastic anemia with antithymocyte globulin (ATG) and cyclosporin leads to clinical remission in a large proportion of patients. As many as 10% to 57% of these patients, however, develop paroxysmal nocturnal hemoglobinuria (PNH). We and others have observed that this secondary PNH appears to be more indolent than classical PNH, which results from an acquired mutation in the PIG-A gene. In the present study, we compared PIG-A mRNA transcripts in affected cells from patients with secondary PNH and patients with classical PNH. All four of our aplastic patients who developed PNH had a negative Ham test at diagnosis. Two of the four showed a positive Ham test within 3 months after ATG/cyclosporin administration, one developed a positive test at 6 months, and another at 18 months after immunosuppressive therapy. All four patients remain transfusion-independent with no thrombotic episodes after a mean follow-up of 30 months (range, 6 to 63 months). Reverse transcription-polymerase chain reaction (RT-PCR) of PIG-A transcripts in DAF-/CD59- neutrophils or lymphocyte lines of the four patients showed PIG-A abnormalities in all cases. Transition of C163 to T was found in one, a 14-bp deletion (positions 1141 to 1154) was found in the second, deletion of C39 was found in the third, and two mutations, transition of C55 to T and transversion of T762 to A, were found in the fourth. These abnormalities compared with findings of abnormal RNA splicing causing a 133-bp deletion, a 4-bp insertion (between positions 578 and 579), loss of A767, and loss of C575 in four patients with primary PNH. We conclude that secondary PNH that evolves out of aplastic anemia, like classical PNH, is associated with mutations in the PIG-A gene. The apparent indolent nature of this disease probably reflects early detection.
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PMID:Genetic defects underlying paroxysmal nocturnal hemoglobinuria that arises out of aplastic anemia. 854 58

Paroxysmal nocturnal haemoglobinuria (PNH) is defined as a somatic mutation of a clonal population of stem cells. Consequently, when aplastic anaemia (AA) occurs in patients with a history of PNH, allogeneic bone marrow transplantation is considered as the only effective treatment. The impact of immunosuppressive therapy has not been reported in this situation. We present observations of three PNH patients who developed AA and were effectively treated with cyclosporin A (CSA). Because of lack of improvement with other treatments, CSA alone was given at a dose of 5-10mg/kg/d. Complete response (CR) was obtained in two patients after 6 and 24 months respectively. A partial response (PR) was observed in the third patient after 12 months. Transient elevated LDH and haemosiderinuria persisted in all cases. DAF and MIRL deficiency were still documented in the two patients in CR. Two patients (one CR, one PR) ceased CSA therapy after 12 months and relapsed within 3-6 months. CSA was reinitiated and led to platelet recovery in one patient after 6 months. The persistence of the abnormal PNH clone is coherent with the hypothesis that CSA does not act directly on the PNH clone but probably acts through regulation of the inhibitory effects of immunocompetent cells on haemopoiesis. These observations suggest that patients suffering from severe AA complicated PNH should not be excluded from immunosuppressive therapy.
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PMID:Correction of aplastic anaemia complicating paroxysmal nocturnal haemoglobinuria: absence of eradication of the PNH clone and dependence of response on cyclosporin A administration. 861 73

The review outlines developments in research on paroxysmal nocturnal haemoglobinuria (PNH). The disease is due to a somatic mutation of the PIG-A gene. This results in deficiency of the protein, GPI (glucosyl phosphatidyl inositol), which serves as an anchor for several membrane-bound proteins including MIRL (CD59; membrane inhibitor of reactive lysis) and DAF (CD55; decay accelerating factor). The absence of these proteins results in increased cellular sensitivity to complement-mediated lysis, affecting not only red cells, leukocytes and platelets, but also haemopoietic stem cells. This explains the often complex clinical picture in PNH (haemolysis, pancytopenia and increased thrombotic predisposition), and the well known relationship between PNH and aplastic anaemia.
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PMID:[PNH--paroxysmal nocturnal hemoglobinuria. An old disease explained by new technology]. 942 27

The peripheral blood cells of ten patients with biopsy-proven aplastic anemia were studied by means of flow-cytometry in order to assess the expression of two phosphatidylinositol-anchored surface proteins: CD55/DAF (decay accelerating factor) and CD59/MIRL (membrane inhibitor of reactive lysis). An abnormal expression was found in five of these ten patients, whereas the "traditional" tests for paroxysmal nocturnal hemoglobinuria (PNH) were positive only on two of these five individuals. Five of the aplastic patients were treated with anti-thymocyte globulin and cyclosporin-A and three entered a complete remission; of the latter, one had CD55/CD59 deficiencies whereas two did not. Along the study period one patient with a hemolytic pattern of PNH was identified. It is concluded that CD55 and/or CD59 abnormalities are frequent in Mexican mestizo patients with aplastic anemia, that the aplastic presentation of PNH is more frequent in Mexico than the hemolytic presentation, that the flow-cytometric identification of CPI-anchored proteins is more sensitive than the "traditional" PNH tests, and that some patients with PNH-aplasia may respond to intensive immunosuppressive treatment. The flow-cytometric identification of GPI-anchored cell surface proteins should replace the "traditional" tests in the identification of patients with PNH.
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PMID:[Glycosilphosphatidylinositol-anchored cell surface protein deficiency in Mexican mestizo patients with aplastic anemia]. 1034 61

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal disorder in which intravascular hemolysis results from the somatic mutation of the totipotent stem cells causing an intrinsic defect in red cell membrane. PNH cells lack glycosylphosphatidylinositol (GPI) anchored membrane proteins. Of these proteins absence of CD 59 (MIRL--membrane inhibitor of reactive lysis, protectin) and CD 55 (DAF--decay accelerating factor) makes the PNH cells abnormally sensitive to the lytic action of complement. The defect appears to be in the somatic mutation of the X-linked PIG-A (phosphatidylinositolglycan A class) gene which participate in an early step of GPI-anchor synthesis. PNH is characterized by recurrent life threatening venous thromboses and an intimate association with aplastic anemia (AA). It seems that PNH always coexists with bone marrow failure (BMF) (37). The possible explanation may be that some GPI-anchored proteins may be a critical target recognized by immune effector cells. PNH clones not possessing these critical GPI-anchored proteins will survive because they are selectively resistant to the autoimmune assault that eliminates most normal clones. The flow cytometry of erythrocytes using anti-CD 59 and anti-CD 59 and anti-CD 55 of granulocytes has been now introduced as a very sensitive and quantitative method of PNH diagnosis able to detect PNH cells even in normal individuals (1,54). Thus it seems now clear that we must make distinction between the detection of very occasional PNH cells in patients with BMF and PNH as a clinicohematological entity. Unfortunately, we do not know the minimal content of PNH cells required to produce clinical signs of PNH (38).
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PMID:Paroxysmal nocturnal hemoglobinuria (membrane defect, pathogenesis, aplastic anemia, diagnosis). 1093 78