title: Mechanisms of anti-D action in the prevention of hemolytic disease of the fetus and newborn.
abstract: Anti-D is routinely and effectively used to prevent hemolytic disease of the fetus and newborn (HDFN) caused by the antibody response to the D antigen on fetal RBCs. Anti-D is a polyclonal IgG product purified from the plasma of D-alloimmunized individuals. The mechanism of anti-D has not been fully elucidated. Antigenic epitopes are not fully masked by anti-D and are available for immune system recognition. However, a correlation has frequently been observed between anti-D-mediated RBC clearance and prevention of the antibody response, suggesting that anti-D may be able to destroy RBCs without triggering the adaptive immune response. Anti-D-opsonized RBCs may also elicit inhibitory FcgammaRIIB signaling in B cells and prevent B cell activation. The ability of antigen-specific IgG to inhibit antibody responses has also been observed in a variety of animal models immunized with a vast array of different antigens, such as sheep RBCs (SRBC). This effect has been referred to as antibody-mediated immune suppression (AMIS). In animal models, IgG inhibits the antibody response, but the T-cell response and memory may still be intact. IgG does not mask all epitopes, and IgG-mediated RBC clearance or FcgammaRIIB-mediated B-cell inhibition do not appear to mediate the AMIS effect. Instead, IgG appears to selectively disrupt B cell priming, although the exact mechanism remains obscure. While the applicability of animal models of AMIS to understanding the true mechanism of anti-D remains uncertain, the models have nevertheless provided us with insights into the possible IgG effects on the immune response.
authors.affiliation: Canadian Blood Services, Department of Laboratory Medicine of St. Michael's Hospital, Toronto, Ontario, Canada.
authors.forename: Davor
authors.initials: D
authors.lastname: Brinc
authors.forename: Alan H
authors.initials: AH
authors.lastname: Lazarus
mesh_terms: D000328:Adult; D000818:Animals; D002417:Cattle; D004195:Disease Models, Animal; D004899:Erythroblastosis, Fetal / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D004910:Erythrocyte Membrane / Q000276:immunology; D005260:Female; D005312:Fetal Blood / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000627:therapeutic use; D007231:Infant, Newborn; D007518:Isoantibodies / Q000096:biosynthesis / Q000276:immunology / Q000627:therapeutic use*; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000276:immunology; D051379:Mice; D016513:Mice, SCID; D008822:Mice, Transgenic; D018448:Models, Immunological; D009895:Opsonin Proteins / Q000276:immunology; D010587:Phagocytosis; D011247:Pregnancy; D011817:Rabbits; D051381:Rats; D017452:Receptors, IgG / Q000037:antagonists & inhibitors / Q000276:immunology; D012203:Rh Isoimmunization / Q000628:therapy*; D012204:Rh-Hr Blood-Group System / Q000276:immunology*; D018029:Rho(D) Immune Globulin
chemical_list: C499173:FCGR2B protein, human; D007074:Immunoglobulin G; D007518:Isoantibodies; D009895:Opsonin Proteins; C061961:RHO(D) antibody; D017452:Receptors, IgG; D012204:Rh-Hr Blood-Group System; D018029:Rho(D) Immune Globulin; C026410:Rho(D) antigen