Blood-group Antibodies and Red-cell Destruction--II

Mollison, P. L.

doi:10.1136/bmj.2.5160.1123

Cited by 34 publications

(12 citation statements)

References 17 publications

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“…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.…”

Section: Methodsmentioning

confidence: 99%

“…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).…”

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confidence: 99%

“…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).…”

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confidence: 99%

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

Atkinson¹,

Frank²

1974

J. Clin. Invest.

140

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A B S T R A C T Purified human IgM isoagglutinins wereutilized to sensitize 'Cr-labeled erythrocytes so as to produce a known number of complement-fixing sites.These cells were then reinfused into the erythrocyte donor. A minimum of 20 Cl-fixing sites/erythrocyte were required for decreased survival. As the amount of antibody coating the erythrocytes was increased, a larger percentage was sequestered. With 80 Cl-fixing sites, more than 75% of the injected erythrocytes were removed from the circulation within 10 min. In each case, the clearance pattern consisted of rapid hepatic sequestration followed by a gradual return of a portion of the erythrocytes into the circulation where they survived normally.Clearance was shown to be dependent upon activation of the classical complement pathway, since sensitized cells survived normally in hereditary angioedema patients with low levels of C4 and no detectable C2. Exposure of sensitized cells to fresh serum for 15 min led to the deposition of 550-800 C3 molecules/Cl-fixing site. Such cells were immune adherence positive, were agglutinated by anti-C3b, formed rosettes with human alveolar macrophages, and were sequestered in vivo, presumably because of the interaction of cell-bound C3b with the C3b receptor on hepatic macrophages. After exposure to heated serum as a source of the C3b inactivator, the cells were immune adherence negative, were agglutinated only by anti-C3d, did not form rosettes with macrophages, and survived normally in vivo despite, being Coombs positive. Cleavage of cell-bound C3b to C3d may explain the release phase of the IgM clearance pattern. Whereas erythrocytes coated with IgM antibody and complement were previously thought to be sequestered in the liver because of extensive membrane damage, these experiments

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Section: Methodsmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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

Atkinson¹,

Frank²

1974

J. Clin. Invest.

140

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“…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.…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

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confidence: 99%