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)

A 16 year old boy underwent allogeneic bone marrow transplantation (BMT) from an human leukocyte antigen (HLA)-identical sibling for severe aplastic anaemia. He was symptomatic for 7 years before transplantation and had received multiple red blood cell and platelet transfusions. Conditioning for BMT consisted of cyclophosphamide, antilymphocyte globulin and total lymphoid irradiation. Engraftment was rapid, there was no evidence of rejection despite the history of multiple blood product transfusions and he did not develop acute or chronic graft versus host disease. He was well for the first 8 months after transplantation but then developed fevers, interstitial pneumonia, herpes simplex infections and cytomegalovirus enteritis. Serological studies revealed antibodies to human immunodeficiency virus (HIV) and he was considered to have acquired immune deficiency syndrome (AIDS). Retrospective analysis of the serum samples showed that he was seronegative for HIV until approximately 10 months before transplantation when his serum became HIV positive. Lymphocyte function studies done after transplantation suggested immunologic recovery at 3 months post-transplant with a brisk though subnormal response to phytohaemagglutinin stimulation. T cell subset analysis performed subsequently showed complete absence of CD4 positive cells indicating immune incompetence which was associated with clinical features of AIDS. Bone marrow transplantation had failed to produce sustained immunologic reconstitution and prevent the progression of HIV to which he ultimately succumbed.
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PMID:Failure of allogeneic bone marrow transplantation to benefit HIV infection. 149 64

Peripheral blood lymphocytes from 25 allogeneic bone marrow transplant recipients were studied serially using flow cytometry and two colour analysis. Fourteen patients were transplanted for haematologic malignancies, eight for aplastic anaemia, two for congenital immunodeficiencies and one for Morquio's disease. All patients were alive more than 100 days post-grafting; nine patients had chronic graft-versus-host disease (GVHD). Dual labelling with monoclonal antibodies, CD4/2H4, CD4/4B4, CD8/CD11, CD8/HLA-DR and CD8/Leu 7 was used to analyse the surface phenotypes of lymphocytes. The population of CD4+2H4+ cells was decreased, and CD8+CD11+, CD8+CD11- and CD8+Leu7+ cells were markedly increased in patients with chronic GVHD. The increase of CD8+CD11+, CD8+CD11- and CD8+Leu7+ cells closely correlated with clinical signs of chronic GVHD in each patient. These results suggest that CD8+ cells may play an important role in effector and/or suppressor mechanisms of chronic GVHD and could be used as an indicator of need for and response to treatment.
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PMID:Increased numbers of CD8+CD11+, CD8+CD11- and CD8+Leu7+ cells in patients with chronic graft-versus-host disease after allogeneic bone marrow transplantation. 169 37

T cell clones were established from peripheral blood of a patient with severe aplastic anemia. 8 of 18 individual clonal T cell populations stably coexpressed CD4 and CD8 molecules, a phenotype characteristic for thymocytes and a minor subpopulation of circulating T lymphocytes. Analysis of T cell receptor genes revealed identical rearrangements of T cell receptor beta chain genes, suggesting clonality of these T cells. CD4+/CD8+ T cells clones were found to be efficiently cytotoxic towards autologous lymphoblasts. Autocytotoxicity could be blocked by a CD3 MAb, a MAb specific for monomorphic MHC class II determinants, and particularly, by an MHC-DP-specific MAb, suggesting specificity for autologous DP molecules. Perhaps more important, CD4+/CD8+ T cell clones inhibited differentiation of autologous progenitor enriched bone marrow cells in vitro by a direct cell-mediated mechanism. These data suggest that circulating cytotoxic CD4+/CD8+ T cell clones specific for autologous MHC-DP determinants may be involved in hematopoietic failure in some cases of aplastic anemia.
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PMID:Clonal analysis of CD4+/CD8+ T cells in a patient with aplastic anemia. 182 29

T-lymphocytes form the peripheral blood of 12 patients with aplastic anemia (AA) and 4 patients with aplastic anaemia-paroxysmal hemoglobinuria syndrome (AA-PNH) were cultivated and their subsets were measured by monoclonal antibodies CD4, CD8, CD25 with indirect immunofluorescence technique. Change of the proportion of T-lymphocyte subsets was observed in 5 patients with AA after the mononuclear cells were activated with phytohemagglutinin (PHA). Its was shown that the number of CFU-T of the patients with AA was apparently decreased in comparison with that of normal controls (P less than 0.05). Disorder of T-lymphocyte subsets took place in patients with AA. The percentages of CD8 and CD25 lymphocytes were increased. The helper: suppressor T-lymphocytes (CD4:CD8) ratio was significantly increased (P less than 0.01). In the cases of AA-PNH, the number of CFU-T was significantly increased (P less than 0.01) and that of T-lymphocyte subsets did not change. The ratio of CD4/CD8 in 5 patients with AA was further decreased after activating mononuclear cells with PHA. These results showed that the increase of T-lymphocytes in patients with AA may account for the low level of CFU-T; the high level of CFU-T in patients with AA-PNH may be related to the multiplication of bone marrow cells. However, there may be a potential disorder of immune system on patients with AA at the same time.
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PMID:[Study on T-lymphocyte culture and function of T-lymphocyte subsets in patients with aplastic anemia]. 183 45

Therapy with antilymphocyte globulin (ALG) has been shown to be effective in restoring hematopoiesis to some patients with aplastic anemia. It would be useful to have a method for predicting those likely to be responders versus nonresponders. The mode of immunostimulatory action of ALG is of interest in addition to its immunosuppressive action. We examined in vitro the distribution of the proliferative responses of ALG-stimulated peripheral blood mononuclear cells (PBMCs) obtained from 18 patients with aplastic anemia, eight of whom responded to ALG and 10 who did not. We found a significant difference in the proliferative response of PBMCs obtained from the eight responders versus the 10 nonresponders (P less than .01). Two-color flow cytometry analysis of the patients' PBMCs stimulated by ALG in vitro showed that the CD4-positive subsets were activated to a greater extent by ALG than the CD8-positive subsets. Moreover, a positive correlation with the clinical response of patients to ALG with granulocyte-macrophage colony-stimulating factor produced by their PBMCs stimulated by ALG suggests that the immunostimulatory property of ALG has an important role in the treatment of aplastic anemia. Our results suggest that the clinical response to ALG therapy is correlated with its lymphocyte proliferative effect in vitro, and indicates that the assessment of the proliferative response of PBMCs in vitro would be useful in predicting the clinical response to ALG therapy.
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PMID:Correlation of response of aplastic anemia patients to antilymphocyte globulin with in vitro lymphocyte stimulatory effect: predictive value of in vitro test for clinical response. 202 81

Four patients with severe aplastic anemia and one patient with pure red cell aplasia (PRCA) were treated with antilymphocyte and antithymocyte globulins. One patient in aplastic anemia who achieved good response by ALG administration had a possible diagnosis of myelodysplastic syndrome. ATG was administered to only one case of aplastic anemia and ALG was administered to the remainder. In the result, three out of 4 patients with aplastic anemia and one patient with PRCA achieved good response without severe side effects. Three patients with aplastic anemia had high CD4/CD8 ratio in their peripheral lymphocytes. This ratio normalized after ALG therapy in effective cases, but not in ineffective case. Natural killer activity elevated after ALG therapy in two effective cases of aplastic anemia and PRCA, but not in one ineffective case of aplastic anemia.
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PMID:[Effectiveness of antilymphocyte and antithymocyte globulins for patients with severe aplastic anemia and pure red cell aplasia--analysis of immunologic parameters of peripheral lymphocytes concerning ALG and ATG therapy]. 210 42

The following immunological studies were performed in circulating mononuclear cells of 17 patients with severe aplastic anemia (SAA): a) lymphocytic phenotypes; b) proliferative response to PHA; c) determination of interleukin 2 (IL2) production and d) expression of Tac CD25. Fifteen of the seventeen patients showed altered CD4/CD8 regulatory populations, expressed as a significantly diminished CD4/CD8 ratio (0.72 +/- 0.19, NV: 1.8 +/- 0.6) (Table 1). The proliferative response to PHA was normal in 80% of the cases; only 2 of the patients showed a diminished response to the mitogen (Fig. 1). IL2 production by PHA-stimulated mononuclear cells was significantly increased (56.6 +/- 9.8; NV: 11 +/- 7.69) (Fig. 1), and a deficient expression to CD25 antigen was also recorded (Table 2). In the other two patients, we observed a normal CD4/CD8 ratio (Table 1, patients 1 and 2) with absence of proliferative response to PHA and hypo-production of IL2 (Fig. 1). These results suggest that in these two cases the hematopoietic defect could be associated to a primary deficiency of cellular immunity. Our results support the current concept of diversity of pathogenetic mechanisms implicated in SAA, and suggest that there are groups of patients with variable degrees of immunological defect that can be delineated through laboratory assays. On the other hand, the altered distribution of regulatory populations mostly due to an absolute decrease of the CD4 subpopulation, associated to the hyperproduction of IL2 and deficient expression of the Tac antigen in most of our patients, suggest the existence of functional alterations.
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PMID:[Changes in distribution of T subpopulations in the peripheral blood of patients with severe idiopathic anemia]. 213 Feb 43

The development of alloantibodies to platelets is a major problem in the supportive management of thrombocytopenia in patients with severe aplastic anemia. We report here a case of aplastic anemia refractory to platelet transfusion. An immunosuppressant, cyclosporin A, which was used for the therapy of aplastic anemia, modulated alloimmunization to platelets in this patient, followed by repeated platelet transfusion. The treatment reduced platelet alloantibodies detected by anti-human immunoglobulin lymphocytotoxicity test, with change of the CD4/CD8 ratio in T lymphocytes in peripheral blood. These results suggest the usefulness of cyclosporin A for the prevention of platelet alloimmunization.
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PMID:Treatment of platelet-alloimmunization with cyclosporin A in a patient with aplastic anemia. 230 81

Thirty-one patients (pts) with aplastic anaemia (AA) were studied whose probable etiology were: idiopathic (16 pts), nocturnal aroxysmal haemoglobinuria (NPH) (2 pts), benzene (4 pts), agrotoxics (5 pts), pharmaceutical drugs (2 pts) and insecticides (2 pts). A decrease in total lymphocyte counts was seen in 10 pts belonging mainly to the NPH and pharmaceutical drug groups, whereas, in the benzene group the opposite was found. B cell levels were low in 9 out of 20 pts. T cell levels varied, the majority of patients had normal levels, 13 presented low levels and 4 had increased numbers. CD4 levels were low in 14 pts and T cell numbers were compensated in some by an increase in CD8 cells. Our results show that there is a great heterogeneity among the patients and there might be differences in the immunological profile of aplastic anaemia depending on the causative agent of the disease.
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PMID:Study of lymphocyte populations and natural killer activity in severe aplastic anaemia. 257 48

Corticosteroids and anti-thymocyte globulin (ATG) have been extensively used in the treatment of autoimmune diseases, aplastic anemia and organ graft rejection; nonetheless, the precise mechanisms of action of these agents are unknown. Studies of their long term immunoregulatory effects, particularly in humans, have been limited. We examined the long term effects of therapy with ATG given for 2-4 weeks and prednisone for 2 months in 4 patients with newly diagnosed insulin dependent diabetes (IDD). Three matched newly-diagnosed untreated IDD patients and 17 healthy volunteers served as controls. No differences in total lymphocyte count, percentage of B cells, percentage of total T cells (CD3), helper-inducer T cells (CD4) or cytotoxic-suppressor cells (CD8), lymphocyte blastogenesis assays, or pokeweed mitogen-induced IgG secretion in T & B cell co-cultures were detected before therapy. A transient lymphopenia following ATG administration was the only immunological defect found in the first month of therapy. At 2 months, however, patients treated with ATG and prednisone had diminished immunoregulatory T cell function demonstrated by production of only 28 +/- 3% IgG expected in T & B co-culture, compared to 205 +/- 35% for untreated IDD patients and 107 +/- 13% for normals (p less than 0.01). This diminished IgG production resulted from excessive suppressor function, since co-cultures of T cells from treated patients with T and B cells from normal volunteers suppressed the latter's IgG production by 76 +/- 9%. This enhanced suppressor activity persisted for 3-6 months following therapy. Other immunological functions were not statistically different from those present at the inception of the study. Thus, treatment with corticosteroids and ATG produces long-term enhanced suppressor activity, a finding which suggests that treatment with combination ATG and Prednisone is a rational form of immunomodulation in conditions associated with decreased suppressor function.
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PMID:Long-term immunoregulatory effects of therapy with corticosteroids and anti-thymocyte globulin. 269 66


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