A role for red cell clearance in antibody‐mediated inhibition of erythrocyte alloimmunization?

Abstract

Antibodies targeting erythrocytes can induce antibody‐mediated inhibition of erythrocyte alloimmunization, and anti‐D has been extremely successful in preventing haemolytic disease of the foetus and newborn (HDFN). It is desirable to replace the current donor‐derived anti‐D with a monoclonal antibody; however, the exact mechanism of IgG‐mediated suppression of red blood cell immune responses remains unclear. It has been proposed that the ability of anti‐D to prevent HDFN is due to IgG interactions with Fc receptors on phagocytic cells leading to rapid clearance of RhD+ red cells. Several monoclonal anti‐D alternatives have been developed with an emphasis on their ability to rapidly clear red blood cells from the circulation. None of the monoclonal antibodies have been as effective as donor‐derived anti‐D with some antibodies inadvertently leading to immune enhancement instead of inhibition. A better understanding of the mechanisms of IgG‐mediated inhibition of red cell alloimmunization is necessary. In this brief review, we highlight selected evidence for and against the requirement for rapid red cell clearance in the ability of IgG to prevent red cell alloimmunization. We also discuss potential alternative mechanisms which could be important for informing the future development of monoclonal antibody alternatives.

Murine models for studying treatment, prevention and pathogenesis of FNAIT

“…Still it is unclear exactly how passively injected antibodies suppress the immune system, but different mechanisms are proposed, as discussed by Kumpel and Elson [50]. Briefly, this includes inhibition of B cells through crosslinking of the B-cell receptor and the inhibitory receptor FcγRIIB on B cells with the antibody-antigen complex, or clearance of antigens, where the antigen is removed from the circulation before the antigen is seen and processed by the immune system [51]. However, Bernardo and colleagues could induce AMIS in knockout mice for either activating or inhibitory Fcγ receptors [52].…”

Immunoglobulin G Fc glycans are not essential for antibody-mediated immune suppression to murine erythrocytes

“…The ability of anti-D to prevent HDFN has long been thought to be due to IgG interactions with Fc receptors on phagocytic cells, leading to rapid clearance of the erythrocytes. 11 IgG interactions with Fc receptors after removal of the conserved Fc N-linked glycan are impaired. 4 The 2 Duffy-specific mAbs (MIMA 29; IgG2a and CBC-512; IgG1) used in this study induce clearance of HOD-RBCs in vivo.…”