Although hematopoietic cells with a paroxysmal nocturnal hemoglobinuria (PNH) phenotype have been often detected in patients with aplastic anemia (AA), their pathologic significance remains unclear. To clarify this point, we examined peripheral blood of 100 patients with AA for the presence of granulocytes deficient in glycosylphosphatidylinositol (GPI)-anchored proteins using a sensitive flow cytometric assay. When 105 peripheral blood granulocytes from 68 normal individuals were examined using phycoerythrin-labeled anti-CD 11 monoclonal antibodies (mAb) as well as FITClabeled anti-CD55 and anti-CD59 mAb, a small number of CD55CD59CDllb* cells were detected in 18 (26.5%) individuals although the frequency of the PNH granulocytes did not exceed 0.003% in any of them. An increase in the frequency of PNH granulocytes (0.003%) was observed in 31 of 35 (88.6%) patients with untreated AA at diagnosis. The proportions of patients showing increased PNH granulocytes was 68.8% (11/16) in treated AA patients with a short (<5 years) disease duration and 20.4% (10/49) in those with a long (5 years) disease duration (P=0.008, x2 test). In treated patients, other factors than time from diagnosis, such as type of therapy, disease severity and requirement for transfusion at sampling did not significantly affect the incidence of showing increased PNH granulocytes. When 19 patients showing increased frequency of PNH granulocytes before therapy were studied at 6-12 months after antithymocyte globulin plus cyclosporine A therapy, the frequency decreased to 0.01-90% of pretreatment values in 15 recovering patients although the absolute number of PNH granulocytes remained unchanged. The frequency increased in the other 3 recovering patients and in one patient refractory to the therapy. These findings suggest that an increase in the number of PNH granulocytes is a common feature of AA at diagnosis, and that it may represent the presence of immunologie pressure to normal hematopoietic stem cells as a cause of AA.
|Original language||English (US)|
|Issue number||11 PART I|
|State||Published - 2000|