Characteristics of I and i antigen receptors on the membrane of erythrocytes in sickle cell anemia.

In this study we employed two approaches in attempts to explain the increased expression of I and i antigens on the membrane surface of SS erythrocytes: immunoelectron microscopy and measurements of antigen-antibody affinity. AA and SS erythrocytes were first reacted with anti-I or anti-i antisera, and then with ferritin-conjugated anti-human IgM. With both antibodies, proportions of cells labeled and ferritin-cluster density on labeled cells were greater for SS erythrocytes at a high level of significance. Studies on the temperature dependence of agglutination by anti-I provided the association constants of agglutination, which were uniformly greater for SS erythrocytes. I and i antigen determinants are carried principally on band 3, the major transmembrane protein of the erythrocyte membrane. Therefore, for SS erythrocytes, the increased I (and i) antigen density and the increased association constant of agglutination by anti-I very likely both reflect the same phenomenon: a relatively greater exposure of I (and i) antigen determinant sites at the membrane surface. Any deviation from normal at the exterior surface of the erythrocyte membrane deserves to be suspect for potential pathogenicity, because this is the cell's region of intimate contact with other elements of the circulation. In addition to enhancing susceptibility of SS erythrocytes to cold agglutinins, an altered exposure of band 3 at the membrane outer surface has the potential for accelerating recognition and removal of SS erythrocytes from the circulation by mononuclear phagocytes.