Stem cells in paroxysmal nocturnal haemoglobinuria and aplastic anaemia: increasing evidence for overlap of haemopoietic defect.
The clinical association between paroxysmal nocturnal haemoglobinuria (PNH) and aplastic anaemia (AA) has long been recognized. Haemolytic PNH, as confirmed by a positive Ham's test, can occur in the setting of AA, and conversely AA can be a late complication of PNH. With the development of sensitive flow cytometry to quantify the expression of phosphatidylinositolglycan (PIG)-anchored proteins on blood cells, a small PNH clone can now be detected in a large number of patients with AA at diagnosis. PIG-A gene mutations can also be demonstrated in some AA patients. In haemolytic PNH, there is always marrow suppression despite a morphologically cellular marrow. In vitro cultures show markedly diminished proliferative capacity in both short-term and long-term marrow cultures, similar to that seen in AA. A similar autoimmune process, through the T-cell cytotoxic repertoire, is probably responsible for the pathogenesis of both AA and PNH. PIG-deficient cells may be resistant to immunological attack by autoreactive cytotoxic T cells, because they lack PIG. They are also more resistant to apoptosis than the PIG-normal cell population. This results in the selection of the PIG-deficient clone, in contrast to the PIG-normal stem cells which possess the PIG anchor and hence are targeted and depleted by the autoreactive T cells.
Marsh
J C W
JC
Department of Haematology, St George's Hospital Medical School, London, UK. jmarsh@sghms.ac.uk
Elebute
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MO
D000328:Adult; D000741:Anemia, Aplastic / Q000276:immunology / Q000473:pathology*; D017209:Apoptosis; D001327:Autoimmune Diseases / Q000473:pathology; D001853:Bone Marrow / Q000473:pathology; D002648:Child; D002999:Clone Cells / Q000473:pathology; D017261:Glycosylphosphatidylinositols / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006457:Hemoglobinuria, Paroxysmal / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D006801:Humans; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics
D017261:Glycosylphosphatidylinositols; D008565:Membrane Proteins; C080086:phosphatidylinositol glycan-class A protein