Expression of Cryptantigen Th on Paroxysmal Nocturnal Hemoglobinuria Erythrocytes in Association with a Hemolytic Exacerbation

Paroxysmal nocturnal hemoglobinuria (PNH) erythrocytes lack complement regulatory membrane proteins and are susceptible to complement. Although the critical role ofcom-plement in intravascular hemolysis in PNH is accepted, the precise mechanism of complement activation in vivo is un-known. Accordingly, in a PNH patient who was suffering from a hemolytic precipitation soon after a common cold-like upper respiratory infection, we analyzed the erythro-cytes with lectins and by flow cytometry to detect membrane alteration that lead to complement activation. The lectin reactivity of erythrocytes showed the expression of cryptan-tigen Th. The patient serum at the time of the hemolysis induced the expression of Th on erythrocytes from PNH patients and from healthy volunteers in vitro, whereas nei-ther the patient serum after recovery from the hemolysis nor blood type-matched control serum from healthy donor showed this activity. Moreover, autologous serum selectively' hemolyzed Th + PNH erythrocytes, but not Th- PNH eryth-rocytes, or Th+ control erythrocytes. Hemolysis was not observed either in complement-inactivated serum or in blood type-matched cord blood serum, which lacks natural antibodies to cryptantigens. These findings indicate that the immunoreaction of infection-induced Th with natural anti-body on PNH erythrocytes is a trigger of the complement activation, leading to intravascular hemolysis. (J. Clin. In-vest. 1995. 96:201-206.) Key words: paroxysmal nocturnal hemoglobinuria * hemolysis * complement activation * crypt-antigen * infectio