Aberrant regulation of complement by the erythrocytes of hereditary erythroblastic multinuclearity with a positive acidified serum lysis test (HEMPAS)

Susceptibility to hemolysis in acidified serum is a pathognomonic feature of hereditary erythroblastic multinuclearity with a positive acidified serum lysis test (HEMPAS, congenital dyserythropoietic anemia type II). The purpose of the studies reported herein was to determine if aberrant regulation of complement contributes to the susceptibility of HEMPAS erythrocytes to acidified serum lysis. The results of these experiments have demonstrated that regulation of both the C3 convertase of the alternative pathway and the membrane attack complex of complement by HEMPAS erythrocytes is aberrant. However, these abnormalities are not a consequence of quantitative or functional deficiencies of the erythrocyte complement-regulatory proteins, decay accelerating factor (DAF, CD55), or membrane inhibitor of reactive lysis (MIRL, CD59). Our recent studies have shown that glycophorin A (GPA), the major erythrocyte sialoglycoprotein is a complement regulatory protein. Analysis by radioimmunoprecipitation suggested that GPA on HEMPAS erythrocytes is abnormally glycosylated. Further analysis indicated that the abnormality involves the O-linked oligosaccharide moiety. Together, these studies show that complement regulation by HEMPAS erythrocytes is abnormal and that constituents other than DAF and MIRL participate in controlling complement activation on the erythrocyte membrane. Additionally, these studies suggest that the glycosylation defect that is characteristic of HEMPAS involves GPA.