Mechanisms of anti-D action in the prevention of hemolytic disease of the fetus and newborn: what can we learn from rodent models?

Abstract

Hemolytic disease of the fetus and newborn can be effectively prevented by administration of anti-D to the mother. In this setting, the IgG purified from the plasma of D-alloimmunized donors prevents the maternal immune response to D-positive red blood cells (RBC). Several monoclonal anti-D antibodies have recently been developed for potential use in the setting of hemolytic disease of the fetus and newborn; the functional assays used to assess the potential success of these antibodies have often assumed antigen clearance as the predominant mechanism of anti-D. Unfortunately, the in-vivo success of these monoclonal antibodies has thus far been limited. A similar inhibitory effect of IgG has been observed in animal models with a vast array of different antigens, referred to as antibody-mediated immune suppression (AMIS). Here, studies of AMIS are reviewed and the relevance of these findings for anti-D-mediated immunoprophylaxis is discussed. In animal models of AMIS, IgG-mediated antigen clearance was not sufficient for prevention of the antibody response to RBC. Furthermore, anti-RBC IgG inhibited B-cell priming to foreign RBC, but failed to prevent a T-cell response and immunological memory. The applicability of AMIS models for determining the true mechanism of anti-D, though uncertain, may nevertheless provide knowledge as to potential mechanisms of action of anti-RBC antibodies.