Mechanisms of anti-D action in the prevention of hemolytic disease of the fetus and newborn
Open Access
- 1 January 2009
- journal article
- review article
- Published by American Society of Hematology in Hematology-American Society Hematology Education Program
- Vol. 2009 (1), 185-191
- https://doi.org/10.1182/asheducation-2009.1.185
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 FcγRIIB 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 FcγRIIB-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.Keywords
This publication has 63 references indexed in Scilit:
- Activation of natural regulatory T cells by IgG Fc–derived peptide “Tregitopes”Blood, 2008
- Immunoglobulin G-mediated regulation of the murine immune response to transfused red blood cells occurs in the absence of active immune suppression: implications for the mechanism of action of anti-D in the prevention of haemolytic disease of the fetus and newborn?Immunology, 2008
- Inflammation enhances consumption and presentation of transfused RBC antigens by dendritic cellsBlood, 2007
- Antibody‐Mediated Regulation of the Immune ResponseScandinavian Journal of Immunology, 2006
- Monoclonal anti-D antibodies to prevent alloimmunization: lessons from clinical trialsTransfusion Clinique et Biologique, 2006
- B cells can prime naive CD4+ T cells in vivo in the absence of other professional antigen‐presenting cells in a CD154‐CD40‐dependent mannerEuropean Journal of Immunology, 2005
- Promotion of B Cell Immune Responses via an Alum-Induced Myeloid Cell PopulationScience, 2004
- IgG Fc ReceptorsAnnual Review of Immunology, 2001
- ANTIBODY SYNTHESIS AT THE CELLULAR LEVELThe Journal of Experimental Medicine, 1965
- Experimental Studies on the Prevention of Rh Haemolytic DiseaseBMJ, 1961