Relation Between Characteristics of Blood‐Group Antibodies in Vitro and Associated Patterns of Red‐Cell Destruction in Vivo

The Destruction of Red Cells by Antibodies in Man. Iii. Quantitative Factors Influencing the Patterns of Hemolysis in Vivo*

“…There is reasonably good, but necessarily indirect, evidence that incomplete agglutinins destroy red cells by rendering them agglutinable in the presence of fibrinogen and other anisometric macromolecules in vivo (2,18), which in turn leads to their low pressure filtration (26) by the spleen. Although it has been postulated that frankly agglutinating antibodies, such as anti-B, cause hepatic trapping by causing large, firm agglutinates which are also filterable by the relatively large liver sinusoids (2), the extensive, comparative studies of human iso-antibodies by Cutbush and Mollison (12,13,27) indicate that those antibodies which bind complement, without producing frank agglutination in vitro, also cause a rapid (probably hepatic) pattern of red cell destruction. Thus, in the present studies, some hepatic sequestration was observed at antibody concentrations which caused little or no agglutination in vitro.…”

“…Thus the liver, with its great mass, is the chief site of trapping. Such hepatic trapping ensues when red cells have been exposed to agglutinating antibodies (1, 2), complement-fixing antibodies (12,13), agglutinating metallic cations (1,3), sodium arsenate (4), and sterile incubation at 370 C for 24 hours or more (5). In general, these alterations involve either gross aggregation of red cells or a nearlytic injury to the cell membrane.…”

Studies on the In Vivo Effects of Antibody INTERACTION OF IgM ANTIBODY AND COMPLEMENT IN THE IMMUNE CLEARANCE AND DESTRUCTION OF ERYTHROCYTES IN MAN

“…Jandl, Jones, and Castle noted a pattern of hepatic sequestration and release on one individual who received erythrocytes coated with anti-B isoagglutinins, although this was thought to be due to the fact that the cells were agglutinated at the time of injection (4). In other studies, injection of erythrocytes coated in vitro with isoagglutinins or injection of type A or B cells into individuals with circulating isoagglutinins to the infused cell type showed a two-part clearance curve (4,(6)(7)(8)(9). There was rapid initial hepatic sequestration or lysis of a large percentage of the injected cells followed by a period of normal or slightly decreased cell survival.…”

“…Early studies demonstrated that erythrocyte sensitization often leads to decreased survival and suggested that sensitization of these cells by antibody in the absence of complement activation results in splenic sequestration due to subtle antibodymediated membrane damage (4,5,8). In contrast, antibodies which mediated the deposition of complement on the cell surface appeared to produce major membrane damage, and such cells were sequestered by reticuloendothelial elements of the liver (4,(6)(7)(8)(9).…”

“…Interest in this condition has focused upon its importance as a model of autoimmune disease in man. Furthermore, it provides a model for the direct exploration of the consequences of cell sensitization by antibody and the mechanisms of cell destruction (2,(4)(5)(6)(7). Early studies demonstrated that erythrocyte sensitization often leads to decreased survival and suggested that sensitization of these cells by antibody in the absence of complement activation results in splenic sequestration due to subtle antibodymediated membrane damage (4,5,8).…”