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)

Identification of HLA-DR, DQ and DP alleles at the DNA level is an important tool for bone marrow transplantation (BMT). We recently encountered an aplastic anemia patient for whom the ability of molecular HLA typing to utilize alternative sources of DNA proved to be fundamental for her treatment. After repeated failures to obtain HLA typing using peripheral blood, HLA-DR and DQ alleles were identified by molecular techniques utilizing two hairs as a source of DNA, ultimately resulting in successful BMT from a sibling donor. This case clearly illustrates the potential of DNA methodologies for HLA typing in patients whose condition precludes the use of more traditional methods.
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PMID:HLA class II DNA typing and subsequent transplantation of an aplastic anemia patient using hair follicles as a DNA source. 799 74

The underlying etiology of aplastic anemia is unknown in the majority of patients, although medications, chemical exposure, or viral infections can be implicated in some. Genetic susceptibility to a variety of diseases has been shown and it has recently been suggested that aplastic anemia is more common in individuals who are HLA DR2+ than in the general population. To examine this question, we retrospectively analyzed the results of HLA-DR typing in 75 aplastic anemia patients who received antithymocyte globulin (ATG) therapy or an HLA-matched sibling bone marrow transplant at UCLA between 1978 and 1989. Thirty-one patients were DR2+, a 1.9-fold higher incidence than the expected number of 16.6 patients (P < .0005). Of the 37 patients who received ATG, 33 were evaluable for a response; 14 patients had either a complete (4 patients) or partial (10 patients) response, for an overall response rate of 42.4%. Of the 14 DR2+ patients who received ATG, 7 responded, for a 50% response rate, which is not significantly higher than the response rate for the DR2- patients (7 of 19 [36.8%]; P = .50). The median survival of patients who are DR2+ was slightly, but not significantly, longer than that of the DR2- patients in the ATG group (P = .19). Although the incidence of HLA DR2 was clearly increased in these patients with aplastic anemia, response rates to ATG were not significantly different in the DR2+ and DR2- patients.
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PMID:An increased HLA DR2 frequency is seen in aplastic anemia patients. 804 74

A unique form of subacute panencephalitis developed in a child with aplastic anemia 8 months after an allogeneic bone marrow transplantation (BMT). It was characterized by parenchymal infiltration of CD3 lymphocytes, a marked increase in the number of microglia strongly expressing HLA-DR antigens in both the gray and white matter, and diffuse degeneration of the cerebral white matter. The onset of neurological symptoms coincided with the development of chronic systemic graft-versus-host disease (GVHD). Cellular infiltrates in the CNS lesions were exclusively CD3 lymphocytes intermingled with a small number of monocytes labeled with CD68. There was a preponderance of cells of the CD45RB phenotype. The pathological changes in visceral organs were consistent with those of chronic GVHD. In addition, scrutiny of immunohistochemistry disclosed sparse infiltration of CD3 lymphocytes and diffuse gliosis in the cerebral white matter of another child with chronic GVHD who died 9 months after allogeneic BMT. These cases are suggestive of a potential risk of CNS involvement in GVHD.
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PMID:Subacute panencephalitis associated with chronic graft-versus-host disease. 849 65

A 67-year-old female was admitted with fatigue. Peripheral blood examination showed severe pancytopenia. Bone marrow biopsy revealed hypoplastic marrow. She was diagnosed as having aplastic anemia. Steroid pulse therapy was not effective. After treatment with erythropoietin (EPO) and granulocyte colony-stimulating factor (G-CSF), blasts which were positive for CD13, CD33, CD34 and HLA-DR and negative for myeloperoxidase appeared in the peripheral blood. At this time, bone marrow biopsy revealed myelofibrosis with increased blasts. Chromosome analysis showed 46XX, add (1) (p36), add (1) (q44), -2, -5, del (7) (q11), -12, +3mar. She died of pneumonia despite chemotherapy with etoposide. Administration of EPO and G-CSF may have led to the rapid development of leukemia and myelofibrosis.
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PMID:[Transformation of aplastic anemia to acute myeloid leukemia with myelofibrosis following treatment with granulocyte colony-stimulating factor and erythropoietin]. 877 84

The existence of T cells capable of inhibiting in vitro hematopoiesis has been shown in aplastic anemia (AA), although whether such inhibition is mediated by a specific immune reaction involving an HLA allele remained unknown. We isolated a CD4+ Vbeta21+ T-cell clone that was most dominant among Vbeta21+ T cells in the bone marrow (BM) of an AA patient whose HLA-DRB1 alleles included 1501 and 0405. The T-cell clone named NT4.2 lysed an autologous Epstein-Barr virus-transformed lymphoblastoid cell line (LCL) and phytohemagglutinin-stimulated lymphocytes (PHA-blasts) as well as allogeneic LCLs sharing HLA-DRB1*0405. Cytotoxicity against LCL cells and PHA-blasts by NT4.2 was blocked by anti-HLA-DR monoclonal antibody (MoAb) or anti-CD3 MoAb. NT4.2 also lysed autologous BM mononuclear cells enriched with CD34+ cells that had been cultured for one week in the presence of colony-stimulating factors as well as allogeneic CD34+ cells of a normal individual carrying HLA-DRB1*0405, cultured in the same way. Moreover, NT4.2 strongly inhibited colony formation by hematopoietic progenitor cells derived from cultured CD34+ cells sharing HLA-DRB1*0405. These results indicate that the AA patient has T cells capable of killing hematopoietic cells in an HLA-DRB1*0405-restricted manner and that such cytotoxic T cells may contribute to the pathogenesis of AA.
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PMID:Isolation of a T-cell clone showing HLA-DRB1*0405-restricted cytotoxicity for hematopoietic cells in a patient with aplastic anemia. 916 Jun 74

In an attempt to elucidate the pathogenic role of a CD4+ cytotoxic T-cell clone NT4.2 isolated from the bone marrow of a patient with cyclosporine-dependent aplastic anaemia, we characterized the T-cell clone as well as its cytotoxicity against an autologous Epstein-Barr (EB) virus-transformed B-lymphoblastoid cell line (LCL). NT4.2 expressed BV21+ BJ2.7+ with a complementarity-determining region (CDR) 3 motif of SQGQGEVEQY which was homologous to that of a T-cell clone isolated from a patient with connective tissue disease. NT4.2 started to lyse LCL cells within 2 h and exerted maximal cytotoxicity within 3 h of incubation. The cytotoxicity required the presence of divalent cations and was not associated with DNA fragmentation of the target cells. Anti-CD59 monoclonal antibodies (MoAb) blocked the cytotoxicity to the same degree as anti-CD3, HLA-DR or CD2 mAb. Flow cytometric analysis of the peripheral blood of this patient during remission after cyclosporine therapy revealed 1.7% of granulocytes to be deficient in CD59. These findings indicate that NT4.2 exerts its cytotoxicity through a perforin-mediated pathway, not a Fas/Fas ligand-dependent pathway, and that haemopoietic stem cells lacking CD59 may evade cytotoxic T lymphocytes, leading to the in vivo expansion of a paroxysmal nocturnal haemoglobinuria clone.
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PMID:Cytotoxicity against lymphoblastoid cells mediated by a T-cell clone from an aplastic anaemia patient: role of CD59 on target cells. 1060 86

It has been reported that aplastic anemia (AA) is more common in HLA-DR2-positive individuals than in the general population. We investigated the frequency of some HLA loci of 102 Northern Han Chinese patients with AA and 105 healthy control subjects. Polymerase chain reaction and sequence specific oligonucleotide probe hybridization were used to determine HLA-DR- and HLA-DR2-related DRB1 alleles. The frequency of DR2 is increased in AA patients; the relative risk (RR) was 2.86, and the difference was significant (chi 2 = 11.1, P = .004). The RR of HLA-DRB1*1501 was 3.07, and the difference was significant (chi 2 = 9.42, P = .008). The above results suggest that HLA-DR2 is significantly associated with AA in Northern Han Chinese. HLA-DRB1*1501 is the main subtype of HLA-DR2, and may be the susceptibility gene of AA.
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PMID:Aplastic anemia is associated with HLA-DRB1*1501 in northern Han Chinese. 1090 54

The association between severe aplastic anemia (AA) and DR2 antigen seems to be well established. However, since discrimination between two DR2-associated splits, namely DR15 and DR16, rarely was performed, it remains unclear whether one or both of these subvariants are responsible for AA susceptibility. In this study, we have analyzed the HLA-DR allelic distribution in a group of 37 AA patients of slavic origin from North-Western Russia. The experimental design included PCR-based amplification of DRB-specific sequences, followed by reverse dot-blot hybridization of the biotinylated PCR-product with the set of sequence-specific oligonucleotide probes. HLA-DRB alleles were identified by non-radioactive enzymatic reaction, then standard serological specificities of HLA-DR antigen were estimated according to the WHO nomenclature. Whereas DR15 subtype occurred more often in the patients (23.0% vs. 13.3%, p< 0.05), DR16 split did not show the same tendency. The results, show the overall predominance of HLA-DR2 specificity (DR15+DR16) did not reach statistical significance (24.4% vs.17.5%, p<0.2). Thus, we conclude that repeatedly reported DR2 frequency increase in AA patients is mainly attributed to the prevalence of DR15 subtype.
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PMID:HLA-DR2 Frequency Increase in Severe Aplastic Anemia Patients is Mainly Attributed to the Prevalence of DR15 Subtype. 1117 35

The degree of histoincompatibility that can be tolerated, and the relative importance of matching at individual HLA class I and class II locus in bone marrow transplantation (BMT) has not been established. We hypothesized that matching for HLA-DR may not be more important than matching for HLA-A or HLA-B in selection of a donor for successful BMT. We retrospectively analyzed the outcomes of 248 consecutive pediatric patients who received allogeneic BMT from related donors (RD, n = 119) or unrelated donors (URD, n = 129). HLA-A and HLA-B were serologically matched, and HLA-DRB1 were identical by DNA typing in 69% of donor-recipient pairs. Most patients (89%) had hematologic malignancies; the rest had aplastic anemia or a congenital disorder. One HLA-A antigen mismatch was associated with a decrease in survival (p = 0.003) and a delay in granulocyte engraftment (p = 0.02) in recipients of RD marrow; as well as a decrease in survival (p = 0.02) and the development of severe acute graft-versus-host disease (GVHD) (p = 0.03) in recipients of URD marrow. One HLA-B antigen mismatch was associated with a decrease in the survival (p = 0.05) and the development of severe GVHD (p = 0.0007) in recipients of RD marrow. One HLA-DRB1 allele mismatch was associated only with a decrease in the survival (p = 0.0003) of recipients of RD marrow. Results of this study suggest that disparity in HLA-A and HLA-B antigens may not be better tolerated than disparity in HLA-DR allele in allogeneic BMT. Further studies are warranted to confirm our results.
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PMID:Effect of HLA class I or class II incompatibility in pediatric marrow transplantation from unrelated and related donors. 1129 73

Fas ligand (FasL) mediated apoptosis in the bone marrow may contribute to suppression of hematopoiesis in myelodysplastic syndromes (MDS) and in aplastic anemia, and also to the regulation of normal erythropoiesis. To identify potential effector and target cells in this regulatory pathway, we examined the constitutive expression of Fas receptor (Fas) and FasL (total and cell-surface) in myeloid and lymphoid cells and subsets of CD34+ cells in normal healthy adult human bone marrow using multiparameter flow cytometry. A high proportion of CD34+ cells constitutively expressed cell-surface FasL. However, none of the CD34+ cells expressed Fas alone. A reciprocal gradient of expression of FasL and Fas was observed in subsets of CD34+ cells: as compared to primitive CD34+/HLA-DR(-) (DR(-)) cells, a higher proportion of committed CD34+/HLA-DR(++) (DR(++)) cells expressed FasL but fewer expressed Fas; the expression of both molecules was intermediate in CD34+/HLA-DR(dim) cells. Also, the intensity of FasL expression was higher in DR(++) than in DR(-) cells. These results suggest that the homeostatic regulation of myelopoiesis in normal bone marrow is mediated via an autoregulatory feedback loop by myeloid cells and progenitors themselves, at least partly via the Fas-FasL pathway. This notion is also consistent with our recent observation that overexpression of FasL by myeloid cells in MDS correlates directly with anemia, transfusion requirements, and shorter survival, an example of dysregulation of this pathway.
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PMID:Constitutive expression of the Fas receptor and its ligand in adult human bone marrow: a regulatory feedback loop for the homeostatic control of hematopoiesis. 1248 10


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