Associations between the <i>HLA-A/B/DRB1</i> polymorphisms and aplastic anemia: evidence from 17 case–control studies

Deng, Xiaozhen; Du, Mi; Peng, Jiao; Long, Jianxiong; Zheng, Chengjun; Tan, Yuan; Li, Lijuan; Cao, Qing; Pang, Yan-Yan; Lan, Yan; Zhang, Haitian

doi:10.1080/10245332.2017.1375064

Cited by 16 publications

(10 citation statements)

References 27 publications

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“…Aplastic anemia is associated with specific histocompatibility antigens 2627 . More striking is the presence of “escape clones”, granulocytes with loss of the region of chromosome 6 that encompasses HLA alleles, in 10–15% of patients 2829,30 ; cells selected by absence of HLA, acquired by 6pLOH or somatic mutations, sustain hematopoiesis by clonal expansion 31 Immune escape has been hypothesized to explain clonal expansion of cells globally deficient in glycosylphosphoinositiol (GPI)-anchored proteins 32 in PNH, due to an acquired mutation in PIG-A in a stem cell.…”

Section: Pathophysiologiesmentioning

confidence: 99%

Aplastic Anemia

2018

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Section: Pathophysiologiesmentioning

confidence: 99%

Aplastic Anemia

2018

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“…AA development has also been associated with specific human leukocyte antigens (HLA) 82 . Class I HLA molecules, such as HLA A02:01, A02:06, A31:01, and B4:02, can act as auto-antigens and are targeted by cytotoxic T cells 83 .…”

Section: Clonalitymentioning

confidence: 99%

“…6pLOH(+) clones have been detected in 11%-13% of AA patients. Reduced HLA auto-antigen expression gives stem cells an opportunity for clonal outgrowth as an "escape" from the autoimmune attack [82][83][84][85][86] . This may be the mechanism by which hematopoiesis is maintained for years in AA patients 83 .…”

Section: Clonalitymentioning

confidence: 99%

High Graft-versus-Host Disease-Free, Relapse/Rejection-Free Survival and Similar Outcome of Related and Unrelated Allogeneic Stem Cell Transplantation for Aplastic Anemia: A Nationwide Swedish Cohort Study

Vaht

Göransson

Carlson

et al. 2019

Biology of Blood and Marrow Transplantation

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Background and aims. Aplastic anemia (AA) is a rare but life-threatening disease. The introduction of immunosuppressive treatment (IST) and hematopoietic stem cell transplantation (HSCT) has considerably improved the outcome of patients with AA. However, modern-day population-based data are limited. This thesis aimed to retrospectively analyze the incidence, treatment modalities, survival, and immune markers in the bone marrow of patients diagnosed with AA in Sweden from 2000-2011. Patients and methods. Patients were included via the National Patient Registry and diagnosed according to the Camitta criteria. All data were collected from medical charts. In paper IV, immunohistochemistry was used to obtain data on regulatory T cells and macrophages in the bone marrow. Results and conclusions. We identified 257 confirmed cases, with an overall incidence of 2.35 cases per million inhabitants per year. The 5-year overall survival (OS) was >90% in patients aged up to 39 years but 38.1% in patients aged ≥60 years. Multivariate analysis showed that age ≥40 years, very severe AA, and no specific therapy were independent risk factors for inferior survival. First-line IST treated patients (n=158) showed a 47% response rate with no difference regarding the age groups or anti-thymocyte globulin (ATG) formulation. The response was significantly associated with the severity grade at the time of treatment initiation, and very severe AA patients exhibited a response rate of 22%. Sixty-eight patients underwent HSCT with a 5-year OS of 86.8%. The graft-versus-host-disease-free, relapse/rejection-free survival at 5 years was 69.1%. Patients aged ³40 years had higher transplant-related mortality that translated into a lower 5-year OS. In paper IV, we found lower numbers of FOXP3-positive regulatory T cells in AA patients without predictive value for IST response and that patients with a higher number of CD163-positive macrophages had a better 5-year OS, but this benefit was only observed in the non-severe AA group. In conclusion, younger patients have very good long-term survival regardless of the choice of therapy, whereas the outcome for patients ≥60 years remains poor. Very severe AA patients respond poorly to ATG, which indicates the need for a different treatment approach.

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“…Babushok et al identified somatic mutation in HLA class I genes including 4 HLA alleles; HLA-A*33.03, HLA-A*68.01, HLA-B*14:02, and HLA-B*40:02, related to more severe disease and predisposing to other chromosomal abnormalities and clonal changes, thus supporting the link between inherited abnormalities and clonal evolution in the course of AA [32]. Also, HLA class II gene related autoimmunity has been revealed [2,[32][33][34][35][36][37]. Comparing AA and hypoplastic MDS patients, including MDS secondary to AA, using SNP array-based karyotyping, Afable et al reported lesions involving the HLA locus suggestive of clonal immune escape in some AA patients [38].…”

Section: Clonal Haematopoiesis Of Hematopoietic Stem Cellmentioning

confidence: 89%

Acquired Aplastic Anemia as a Clonal Disorder of Hematopoietic Stem Cells

Brzeźniakiewicz‐Janus

Rupa‐Matysek

Gil

2020

Stem Cell Rev and Rep

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Aplastic anemia is rare disorder presenting with bone marrow failure syndrome due to autoimmune destruction of early hematopoietic stem cells (HSCs) and stem cell progenitors. Recent advances in newer genomic sequencing and other molecular techniques have contributed to a better understanding of the pathogenesis of aplastic anemia with respect to the inflammaging, somatic mutations, cytogenetic abnormalities and defective telomerase functions of HSCs. These have been summarized in this review and may be helpful in differentiating aplastic anemia from hypocellular myelodysplastic syndrome. Furthermore, responses to immunosuppressive therapy and outcomes may be determined by molecular pathogenesis of HSCs autoimmune destruction, as well as treatment personalization in the future.

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Associations between the HLA-A/B/DRB1 polymorphisms and aplastic anemia: evidence from 17 case–control studies

Abstract: In conclusion, HLA-A/B/DRB1 polymorphisms may play an important role in AA, but higher quality and larger sample studies are needed to confirm.

Cited by 16 publications

References 27 publications

Aplastic Anemia

Aplastic Anemia

High Graft-versus-Host Disease-Free, Relapse/Rejection-Free Survival and Similar Outcome of Related and Unrelated Allogeneic Stem Cell Transplantation for Aplastic Anemia: A Nationwide Swedish Cohort Study

Acquired Aplastic Anemia as a Clonal Disorder of Hematopoietic Stem Cells

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