{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T04:56:57Z","timestamp":1792299417284,"version":"4.4.0"},"reference-count":90,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2015,4,23]],"date-time":"2015-04-23T00:00:00Z","timestamp":1429747200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,5,15]]},"abstract":"<jats:title>Summary<\/jats:title>\n               <jats:p>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)-\u03b3, tumour necrosis factor (TNF)-\u03b1 and transforming growth factor (TGF)-\u03b2, induce apoptosis of HSPCs, constituting a consistent and defining feature of severe aAA. Alterations in the polymorphisms of TGF-\u03b2, IFN-\u03b3 and TNF-\u03b1 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.<\/jats:p>","DOI":"10.1111\/cei.12605","type":"journal-article","created":{"date-parts":[[2015,2,13]],"date-time":"2015-02-13T12:25:33Z","timestamp":1423830333000},"page":"361-370","source":"Crossref","is-referenced-by-count":116,"title":["The complex pathophysiology of acquired aplastic anaemia"],"prefix":"10.1093","volume":"180","author":[{"given":"Y","family":"Zeng","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Steele Children's Research Center, University of Arizona, Tucson, AZ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Katsanis","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Steele Children's Research Center, University of Arizona, Tucson, AZ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,4,23]]},"reference":[{"key":"2021122010152005000_cei12605-bib-0001","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1182\/blood-2011-12-274019","article-title":"How I treat acquired aplastic anemia","volume":"120","author":"Scheinberg","year":"2012","journal-title":"Blood"},{"key":"2021122010152005000_cei12605-bib-0002","doi-asserted-by":"crossref","first-page":"2509","DOI":"10.1182\/blood-2006-03-010777","article-title":"Current concepts in the pathophysiology and treatment of aplastic anemia","volume":"108","author":"Young","year":"2006","journal-title":"Blood"},{"key":"2021122010152005000_cei12605-bib-0003","doi-asserted-by":"crossref","first-page":"310","DOI":"10.3324\/haematol.2008.002329","article-title":"Immunosuppressive treatment for aplastic anemia: are we hitting the 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