Roles of DRB1∗1501 and DRB1∗1502 in the pathogenesis of aplastic anemia

Sugimori, Chiharu; Yamazaki, Hirohito; Feng, Xingmin; Mochizuki, Kanako; Kondo, Yukio; Takami, Akiyoshi; Chuhjo, Tatsuya; Kimura, Akinori; Teramura, Masanao; Mizoguchi, Hideaki; Omine, Mitsuhiro; Nakao, Shinji

doi:10.1016/j.exphem.2006.09.002

Cited by 61 publications

(65 citation statements)

References 34 publications

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“…18 A relatively good response to immunosuppressive therapy for patients with MDS and aplastic anemia was also predicted by expression of HLA-DR15 in studies of both North American and Japanese patients. 24,25 These observations support the hypothesis that aplastic anemia and a subgroup of low-risk MDS are immune-mediated diseases, and that the immune pathophysiological process provides the selection pressure that favors the outgrowth of PIGA mutant, GPI-AP-deficient stem cells.…”

Section: Subclinical Pnhsupporting

confidence: 75%

Management of Paroxysmal Nocturnal Hemoglobinuria in the Era of Complement Inhibitory Therapy

Parker

2011

Hematology

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Despite the availability of safe, effective targeted therapy that controls intravascular hemolysis, the management of paroxysmal nocturnal hemoglobinuria (PNH) remains complicated because of disease heterogeneity and close association with BM failure syndromes. The purpose of this review is to provide a framework for individualizing treatment based on disease classification. According to the recommendations of the International PNH Interest Group, patients can be placed into one of the following 3 categories: (1) classic PNH, (2) PNH in the setting of another BM failure syndrome, or (3) subclinical PNH. The PNH clone in patients with subclinical disease is insufficiently large to produce even biochemical evidence of hemolysis, and consequently, patients who fit into this category require no PNH-specific therapy. Patients with PNH in the setting of another BM failure syndrome (usually aplastic anemia or low-risk myelodysplastic syndrome) have at least biochemical evidence of hemolysis, but typically the PNH clone is small (Ͻ 10%) so that hemolysis does not contribute significantly to the underlying anemia. In these cases, the focus of treatment is on the BM failure component of the disease. Intravascular hemolysis is the dominant feature of classic PNH, and this process is blocked by the complement inhibitor eculizumab. The thrombophilia of PNH also appears to be ameliorated by eculizumab, but the drug has no effect on the BM failure component of the disease. Low-grade extravascular hemolysis due to complement C3 opsonization develops in most patients treated with eculizumab, and in some cases is a cause for suboptimal response to treatment. Allogeneic BM transplantation can cure classic PNH, but treatment-related toxicity suggests caution for this approach to management.

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Section: Subclinical Pnhsupporting

confidence: 75%

Management of Paroxysmal Nocturnal Hemoglobinuria in the Era of Complement Inhibitory Therapy

Parker

2011

Hematology

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“…It is generally considered that DR2 and its subgroups are associated with the effectiveness of pure CsA treatment or enhanced IST, but irrelevant for simple ATG or antilymphocyte globulin (ALG) treatment. Among Japanese AA patients, the reactivity of pure CsA treatment or enhanced IST in DR2 + or DRB1*15:01 + patients was significantly higher than that in DR2 -or DRB1*15:01 -patients (22,(24)(25)(26). However, no difference in the reactivity of pure ATG treatment was observed between these kinds of patients (20).…”

Section: Ist-effective Group (N=49) Healthy Control Group (N=222) ---mentioning

confidence: 74%

Correlation analysis of severe aplastic anemia immunosuppressive therapy and human leukocyte antigen alleles in pediatric patients

Hou

Zhang

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. The aim of the present study was to investigate the correlation between the efficacy of immunosuppressive therapy (IST) in children with severe aplastic anemia (SAA) and human leukocyte antigen (HLA) alleles. The polymerase chain reaction-sequence based typing high-resolution genotyping method was used to profile the HLA alleles of 115 SAA cases that were treated with rabbit-antithymocyte globulin (r-ATG) + cyclosporine (CsA) immunosuppressive therapy and 222 normal control subjects. The aim was to compare the frequency distribution of HLA alleles among the IST-effective group, the IST-ineffective group and the healthy control group.

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“…However, we previously examined various factors, including GPI-AP -cells and DRB1*1501, for their association with good response to IST in 140 patients with AA using multivariate analysis and found that only the presence of increased GPI-AP -cells significantly predicts favorable response to IST. 30,31 Thus, it is unlikely that DRB1*1501 affects PFS of patients with MDS more strongly than increased GPI-AP -cells or high TPO levels. Cytogenetic abnormality was not identified as a poor risk factor by the multivariate analysis.…”

Section: Discussionmentioning

confidence: 99%

Increased plasma thrombopoietin levels in patients with myelodysplastic syndrome: a reliable marker for a benign subset of bone marrow failure

et al. 2013

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ARTICLES 901 Myelodysplastic SyndromesAlthough myelodysplastic syndromes are heterogeneous disorders comprising a benign subset of bone marrow failure similar to aplastic anemia, no laboratory test has been established to distinguish it from bone marrow failures that can evolve into acute myeloid leukemia. Plasma thrombopoietin levels were measured in 120 patients who had myelodysplastic syndrome with thrombocytopenia (< 100 x 10 9 /L) to determine any correlation to markers associated with immune pathophysiology and outcome. Thrombopoietin levels were consistently low for patients with refractory anemia with excess of blasts, while patients with other myelodysplatic syndrome subsets had more variable results. Patients with thrombopoietin levels of 320 pg/mL and over had increased glycosylphosphatidylinositol-anchored protein-deficient blood cells (49.1% vs. 0%), were more likely to have a low International Prognostic Scoring System (IPSS) score (≤1.0, 100% vs. 65.5%), a higher response rate to immunosuppressive therapy (84.2% vs. 14.3%), and a better 5-year progression-free survival rate (94.1% vs. 63.6% for refractory cytopenia with unilineage dysplasia; 100.0% vs. 44.4% for refractory cytopenia with multilineage dysplasia). In conclusion, increased plasma thrombopoietin levels were associated with a favorable prognosis of bone marrow failure and could, therefore, represent a reliable marker for a benign subset of myelodysplastic syndrome. Increased plasma thrombopoietin levels in patients with

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Roles of DRB1∗1501 and DRB1∗1502 in the pathogenesis of aplastic anemia

Cited by 61 publications

References 34 publications

Management of Paroxysmal Nocturnal Hemoglobinuria in the Era of Complement Inhibitory Therapy

Management of Paroxysmal Nocturnal Hemoglobinuria in the Era of Complement Inhibitory Therapy

Correlation analysis of severe aplastic anemia immunosuppressive therapy and human leukocyte antigen alleles in pediatric patients

Increased plasma thrombopoietin levels in patients with myelodysplastic syndrome: a reliable marker for a benign subset of bone marrow failure

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