Paroxysmal nocturnal hemoglobinuria: II. Erythrocyte acetylcholinesterase defect

Markedly reduced erythrocyte acetylcholinesterase activity was demonstrated in all eight cases of paroxysmal nocturnal hemoglobinuria studied. Consistent reduction of this degree has not been noted in other blood dyscrasias, either in studies cited in the literature or in our own investigations. The defect was localized to the stroma of the PNH red cell. The enzyme activity of reticulocytes was markedly impaired, indicating that the immature cells were formed with defective acetylcholinesterase. The activity of normal cells was not reduced following transfusion into patients with PNH. No evidence was found for a circulating inhibitor of acetylcholinesterase or for one which could be readily eluted from the PNH erythrocyte membrane. However, our studies do not exclude the possibility of an inhibitor, particularly one bound firmly to the enzyme. In the one case in which a family study was carried out, normal erythrocyte acetylcholinesterase activity was present in all members tested. The previous work of many investigators has suggested that erythrocyte acetylcholinesterase plays an important role in the preservation of the integrity of the red cell. The significance of the defective enzyme activity in the PNH cell is discussed in this connection.