title: The complex pathophysiology of acquired aplastic anaemia.
abstract: Immune-mediated destruction of haematopoietic stem/progenitor cells (HSPCs) plays a central role in the pathophysiology of acquired aplastic anaemia (aAA). Dysregulated CD8(+) cytotoxic T cells, CD4(+) 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.
authors: Department of Pediatrics, Steele Children's Research Center, University of Arizona, Tucson, AZ, USA.
authors: Y
authors: Y
authors: Zeng
authors: Department of Pediatrics, Steele Children's Research Center, University of Arizona, Tucson, AZ, USA.
authors: E
authors: E
authors: Katsanis
mesh_terms: D000741:Anemia, Aplastic / Q000209:etiology* / Q000378:metabolism / Q000628:therapy; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004198:Disease Susceptibility / Q000276:immunology; D020022:Genetic Predisposition to Disease; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D056747:Immunomodulation; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines
keywords: aplastic anemia; bone marrow mesenchymal stem cell; hematopoietic stem/progenitor cell, immune dysregulation