A pathogenetic link between aplastic anemia and paroxysmal nocturnal hemoglobinuria is suggested by a high frequency of aplastic anemia patients with a deficiency of phosphatidylinositol glycan anchored proteins.
The clinical interrelationship between paroxysmal nocturnal hemoglobinuria (PNH) and aplastic anemia (AA) promoted a search for a pathogenetic link. Since the molecular defect in PNH is a failure to express phosphatidylinositol glycan-anchored proteins (PIG-AP), we investigated whether this defect could also be demonstrated on peripheral blood cells of patients with typical AA. Quantification of the expression of PIG-AP was performed by flow cytometry using the monoclonal antibodies (MAbs) CD16 and CD66b for granulocytes, CD14 and CD48 for monocytes, CD48 and CD52 for lymphocytes, and CD55 and CD59 for erythrocytes. We analyzed cells from 52 patients with acquired AA. A PIG-AP-defective population was identified in 27 of 52 patients (52%) in at least one cell lineage. Granulocytes were involved in 25 of 27, monocytes in 18 of 25, lymphocytes in seven of 27, and erythrocytes in seven of 27 AA patients who were affected by a PIG-AP deficiency. The response rate to standard immunosuppressive therapy was significantly higher in the group of patients without a PIG-AP-deficient population than in patients with a PIG-AP-deficient population in at least one cell lineage (85.7 vs. 30.4%; p < 0.0003). Our results demonstrate that on the basis of PIG-AP expression, the proportion of AA patients who show features of typical AA along with a PNH phenotype is substantially higher than previously recognized. The pattern of PIG-AP expression might identify subgroups of AA patients who differ in the underlying mechanism as well as in the course of their disease.
Schrezenmeier
H
H
Department of Medicine III, University of Ulm, Germany.
Hertenstein
B
B
Wagner
B
B
Raghavachar
A
A
Heimpel
H
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D000741:Anemia, Aplastic / Q000097:blood / Q000209:etiology* / Q000628:therapy; D000911:Antibodies, Monoclonal; D004912:Erythrocytes / Q000737:chemistry; D005260:Female; D005434:Flow Cytometry; D017261:Glycosylphosphatidylinositols / Q000097:blood / Q000172:deficiency*; D006098:Granulocytes / Q000737:chemistry; D006457:Hemoglobinuria, Paroxysmal / Q000097:blood / Q000209:etiology* / Q000628:therapy; D006801:Humans; D007165:Immunosuppression Therapy; D008214:Lymphocytes / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000737:chemistry
D000911:Antibodies, Monoclonal; D017261:Glycosylphosphatidylinositols