Stem cells in paroxysmal nocturnal haemoglobinuria and aplastic anaemia: increasing evidence for overlap of haemopoietic defect.

Abstract

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.