Immunophenotypic discrepancies between granulocytic and erythroid lineagesin peripheral blood of patients with paroxysmal nocturnal haemoglobinuria

In paroxysmal nocturnal haemoglobinuria (PNH), somatic mutation of the PIG- A gene is thought to result in altered expression of glycosylphosphatidylin ositol (GPI)-anchored proteins. This study was performed to determine if th ere were any heterogeneities of cellular phenotypes between two major perip heral blood cells, erythrocytes and granulocytes. Using CD59-based immunocy tometry, the patterns of CD59 expression were shown to be conserved in the circulating erythroid cells (reticulocytes and mature erythrocytes) in all 29 patients with PNH. Twenty-one patients had distinct combinations of PNH type T, II, and III cells in different lineages. Only eight patients exhibi ted similar patterns of CD59 expression between the two lineages. Approxima tely one third of the patients had PNH type II cells in either or both of t he two lineages indicating variable lineage involvement. The proportion of abnormal granulocutes was higher than those of abnormal reticulocytes and e rythrocytes. In patients with appropriate erythropoietic responses to haemo lysis (RPI>2.0), shift reticulocytes display predominantly PNH phenotypes. These immature erythroid cells with altered expression of GPI-anchored prot eins may dominate the peripheral blood during periods of increased marrow a ctivity resulting in greater phenotypic mosaicism in such patients. Discrep ancies in expression of GPI-anchored proteins in PNH which are highly varia ble between the two lineages may be the result of their different life span s and the influence of complement-mediated cytolysis. The phenomena also in dicated the possible occurrence of more than one PNH clones with variable c lonal dominance.