Seeing the good and bad in aplastic anemia: is autoimmunity in AA dysregulated or antineoplastic?
Aplastic anemia (AA) is considered to be an autoimmune disease directed against hematopoietic stem cells (HSC), though knowledge on the inciting autoantigen(s) is scant. According to the traditional concept of autoimmunity the target tissue in autoimmune disease is essentially normal, and misdirected self-attack is caused by disturbed self-recognition. Recently, this theory has been challenged by the hypothesis that autoimmunity against solid tissues is directed against intrinsically abnormal, transforming cells, i.e. autoimmune reactions are essentially antineoplastic, attempting to eliminate cells signalling 'danger'. This theory might apply to AA as well. Observations such as the dysplastic traits typical of non-severe AA, the high prevalence of one or several abnormal hematopoietic clones and their resistance to apoptosis in newly diagnosed AA patients suggest that these cell populations do not develop secondarily, but expand primarily und could be the primary target of AA, normal hematopoietic stem cells being destroyed as innocent bystanders. If bone marrow hypoplasia/aplasia indeed reflects an immune reaction incited by outgrowth of transformed cells, immunosuppressive treatment of AA would have to be reconsidered, since a two-edged sword. As a consequence, AA patients with a hyperreactive immune system may require more intense immunosuppressive therapy (IS), whereas patients with an anergic immune system may fare better with IS of lower intensity than the currently recommended standard.
Department of Hematology, University Hospital, CH-4031 Basel, Switzerland. nissen@magnet.ch
Catherine
C
Nissen
Jörg
J
Schubert
D000741:Anemia, Aplastic / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D017209:Apoptosis; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D015551:Autoimmunity / Q000276:immunology*; D001854:Bone Marrow Cells / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000276:immunology; D002999:Clone Cells / Q000473:pathology; D004913:Erythrocytes, Abnormal / Q000473:pathology; D017261:Glycosylphosphatidylinositols / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000473:pathology; D006801:Humans; D007157:Immunologic Surveillance / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D008565:Membrane Proteins / Q000235:genetics; D018448:Models, Immunological; D009190:Myelodysplastic Syndromes / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000276:immunology / Q000473:pathology; D020183:Nocturnal Paroxysmal Dystonia / Q000235:genetics / Q000473:pathology; D019139:Tumor Escape / Q000276:immunology
D001324:Autoantigens; D017261:Glycosylphosphatidylinositols; D007166:Immunosuppressive Agents; D008565:Membrane Proteins; C080086:phosphatidylinositol glycan-class A protein