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)

Allogeneic stem cell transplantation (allo SCT) is now frequently performed for the treatment of haematological malignancies and aplastic anaemia. However, graft-versus-host disease (GVHD) is still the major complication after allo SCT, producing immune deficiency, infection, organ damage and, occasionally, patient death. The antigen-specific signal mediated by the T-cell receptor (TCR) is essential for activation of T-cells; however, additional co-stimulatory signals are required for complete T-cell activation. Therefore, blocking strategies of co-stimulatory signals have been evaluated as targets of therapeutic intervention for GVHD after allo SCT. In a mouse bone-marrow transplantation (BMT) model, the administration of CTLA4-Ig, which blocks the interaction of CD28 on T-cells and B7 molecules on antigen-presenting cells (APCs), can prolong survival of allo BMT recipients, although this effect was not complete. In addition, the anti-CD40L (CD154) monoclonal antibody (mAb), which can interfere with the interaction of CD154 on T-cells and CD40 on APCs, can induce long-term graft survival in the murine model. Combined administration of CTLA4-Ig and anti-CD40L mAb can prevent allograft rejection in primates. Therefore, it seems the most powerful method to prevent the alloimmune response in vivo. The Fas/Fas ligand pathway is also involved in pathogenesis of GVHD. Anti-FasL mAb can reduce the mortality of GVHD and improve intestinal lesions. Recently, it was reported that donor bone marrow treated ex vivo using CTLA4-Ig reconstituted haematopoiesis in vivo with a relatively low risk of GVHD in human allo BMT. Therefore, selective blocking strategies for T-cell co-signalling might be useful for the prevention of GVHD in human allo SCT.
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PMID:T-cell co-signalling molecules in graft-versus-host disease. 1090 5

Aplastic anemia (AA) is a rare disease with a major autoimmune pathogenetic component. CTLA4 is a T-lymphocyte surface molecule involved in the maintenance of immune tolerance. Some polymorphisms associated with a reduced expression of CTLA4, and thus presumably with increased tendency to autoimmunity, have been associated with various autoimmune diseases. In this study, we evaluated the distribution of the low expression polymorphisms -318C > T and 49A > G of CTLA4 in a population of 67 patients with acquired AA and in 100 normal controls. There was no difference in the distribution of the tested polymorphism between patients and controls and, within the patient group, between those who responded to immunosuppression vs those who did not respond. This study indicates that the polymorphisms -318C > T and 49A > G of CTLA4 do not affect the risk of developing AA and do not influence the response to immunosuppression.
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PMID:The polymorphisms -318C>T in the promoter and 49A>G in exon 1 of CTLA4 and the risk of aplastic anemia in a Caucasian population. 1581 39

To investigate the expression and significance of CD28 and CTLA4 on T cells in bone marrow of aplastic anemia (AA) mice, in vitro bone marrow mononuclear cells (BMMNCs) were activated through being incubated with PHA (15 microg/mL). The expression of CD28 and CTLA4 on T cells incubated with or without PHA was detected by two-color flow cytometry. The expression of CD28 and CTLA4 was significantly increased after PHA stimulation. In the AA mice, the expression of CD28 with or without PHA stimulation was both higher than that in the normal mice (both P < 0.01), but the expression of CTLA4 with or without PHA stimulation showed no significant difference in comparison to that in the normal mice (both P > 0.05). In the AA mice, there were more activation and activated potential of T cells than the normal, and the abnormal expression of CD28 and CTLA4 may participate in immunological disorder mediated by T cells.
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PMID:Expression of CD28 and CTLA4 on T cells in bone morrow of immune-mediated aplastic anemia mice. 1646 58

Bone marrow failure and related syndromes are rare disorders characterized by ineffective bone marrow hematopoiesis and peripheral cytopenias. Although many are associated with characteristic clinical features, recent advances have shown a more complicated picture with a spectrum of broad and overlapping phenotypes and imperfect genotype-phenotype correlations. Distinguishing acquired from inherited forms of marrow failure can be challenging, but is of crucial importance given differences in the risk of disease progression to myelodysplastic syndrome, acute myeloid leukemia, and other malignancies, as well as the potential to genetically screen relatives and select the appropriate donor if hematopoietic stem cell transplantation becomes necessary. Flow cytometry patterns in combination with morphology, cytogenetics, and history can help differentiate several diagnostic marrow failure and/or insufficiency entities and guide genetic testing. Herein we review several overlapping acquired marrow failure entities including aplastic anemia, hypoplastic myelodysplasia, and large granular lymphocyte disorders; and several bone marrow disorders with germline predisposition, including GATA2 deficiency, CTLA4 haploinsufficiency, dyskeratosis congenita and/or telomeropathies, Fanconi anemia, Shwachman-Diamond syndrome, congenital amegakaryocytic thrombocytopenia, severe congenital neutropenia, and Diamond-Blackfan anemia with a focus on advances related to pathophysiology, diagnosis, and management.
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PMID:Acquired and germline predisposition to bone marrow failure: Diagnostic features and clinical implications. 3057 48