The complex pathophysiology of acquired aplastic anaemia

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Immune-mediated destruction of haematopoietic stem/progenitor cells (HSPCs) plays a central role in the pathophysiology of acquired aplastic anaemia (aAA). Dysregulated CD8<sup>+</sup> cytotoxic T cells, CD4<sup>+</sup> T cells including T helper type 1 (Th1), Th2, regulatory T cells and Th17 cells, natural killer (NK) cells and NK T cells, along with the abnormal production of cytokines including interferon (IFN)-γ, tumour necrosis factor (TNF)-α and transforming growth factor (TGF)-β, induce apoptosis of HSPCs, constituting a consistent and defining feature of severe aAA. Alterations in the polymorphisms of TGF-β, IFN-γ and TNF-α genes, as well as certain human leucocyte antigen (HLA) alleles, may account for the propensity to immune-mediated killing of HSPCs and/or ineffective haematopoiesis. Although the inciting autoantigens remain elusive, autoantibodies are often detected in the serum. In addition, recent studies provide genetic and molecular evidence that intrinsic and/or secondary deficits in HSPCs and bone marrow mesenchymal stem cells may underlie the development of bone marrow failure.

Original languageEnglish (US)
Pages (from-to)361-370
Number of pages10
JournalClinical and Experimental Immunology
Volume180
Issue number3
DOIs
StatePublished - Jun 1 2015

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Aplastic Anemia
Hematopoietic Stem Cells
Transforming Growth Factors
Interferons
Tumor Necrosis Factor-alpha
Bone Marrow
T-Lymphocytes
Th17 Cells
Natural Killer T-Cells
Hematopoiesis
Autoantigens
Regulatory T-Lymphocytes
HLA Antigens
Mesenchymal Stromal Cells
Natural Killer Cells
Autoantibodies
Molecular Biology
Alleles
Apoptosis
Cytokines

Keywords

  • Aplastic anemia
  • Bone marrow mesenchymal stem cell
  • Hematopoietic stem/progenitor cell, immune dysregulation

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

The complex pathophysiology of acquired aplastic anaemia. / Zeng, Yi -; Katsanis, Emmanuel.

In: Clinical and Experimental Immunology, Vol. 180, No. 3, 01.06.2015, p. 361-370.

Research output: Contribution to journalArticle

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