ADCC (K‐Cell) Lysis of Human Erythrocytes Sensitized with Rhesus Alloantibodies III. COMPARISON OF IgG ANTI‐D AGGLUTINATING AND LYTIC (ADCC) ACTIVITY AND THE ROLE OF IgG SUBCLASSES

Abstract

Conventional manual (enzyme and antiglobulin titres) and AutoAnalyser quantitation of anti-D sera were compared with the ability of the same sera to mediate lysis of Rh(D) positive red cells in an ADCC assay. AutoAnalyser (AA) quantitation correlated significantly with manual titration methods, although there were wide discrepancies between individual sera. The ADCC activity of the anti-D sera did not correlate with any of the conventional assays (AA, enzyme, antiglobulin). There were significant differences between anti-D sera obtained from females immunized during pregnancy and male volunteers immunized by deliberate injection. The female sera contained significantly less anti-D when assessed by AA, yet were significantly more active in ADCC activity at equivalent concentrations. These functional differences in anti-D activity could not be attributed to the absence of IgG subclasses (IgG1 and IgG3) known to induce ADCC. However, there was a relationship between ADCC and IgG1/IgG3 titres in that high ADCC activity was seen where the IgG3 titre was higher than the IgG1 titre. In the male anti-D sera IgG1 titres were greater than or equal to IgG3 titres and ADCC activity was very low.

A single recombinant anti-RhD IgG prevents RhD immunization: association of RhD-positive red blood cell clearance rate with polymorphisms in the FcγRIIA and FcγIIIA genes

“…There is extensive literature on in vitro functional analysis of Fc-mediated effector functions of monoclonal anti-RhD antibodies via Fc␥R interactions, their utility in predicting prophylactic efficacy, and the relative merits of IgG1 versus IgG3 isotypes with respect to phagocytosis and cytolysis. [23][24][25][26][27][28][29][30][31][32][33][34] Rh prophylaxis is thought to be successful due to the efficient clearance of RhD-positive RBCs from the circulation and phagocytosis of anti-RhD-coated RBCs by macrophages in the spleen. 35 Accelerated clearance of coated RBCs and a relation between the rate of clearance and the degree of coating were observed many years ago.…”

Antibody-Dependent, Cell-Mediated Cytotoxicity of Nucleated Mammalian Cells by Rat Eosinophils and Neutrophils

“…It has been noted that the activity of effector cells involved in antibody-dependent cell-mediated cytotoxicity can vary accordingly to the IgG subclass present in the system [Holm et al, 1973;Urbaniak and Ayoub-Greiss, 1980], and inhibition studies with heat-aggregated IgG subclasses [Greenberg et al, 1973;MacLennan et al, 1973;Holm et al, 1973] have fur ther strengthened this view. Furthermore, Fc receptor differences also exist between eosinophils and neutro phils [Lopez and Sanderson, in preparation].…”

Improved Care for Rh-Isoimmunized Patients in Saudi Arabia

“…Each IgG molecule has an antigen-binding fragment (Fab) and a phagocytic cell-binding fragment or crystallizable fragment (Fc). 39,40 The structural differences between the subgroups are in the level of Fc fragment. IgG 1 and IgG 3 fragments react readily with receptors or phagocytic cells, while IgG 2 and IgG 4 are totally inactive in this aspect.…”

“…In addition, IgG 1 and IgG 3 have different biological properties in respect to production and monocytic fixation capacity. 39,40 IgG 1 is produced early in pregnancy and is transported across the placenta in large amounts in the mid trimester, while IgG 3 response tends to come later. 41 IgG 3 has a greater affinity for phagocytic receptors and thereby small amounts of IgG 3 can cause significant fetal hemolysis.…”