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


RESULTS
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.


CONCLUSIONS
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.
Brinc
Davor
D
The Canadian Blood Services, Toronto, Ontario, Canada.
Denomme
Gregory A
GA
Lazarus
Alan H
AH
D000818:Animals; D004195:Disease Models, Animal; D004899:Erythroblastosis, Fetal / Q000188:drug therapy* / Q000276:immunology; D005333:Fetus; D006801:Humans; D007231:Infant, Newborn / Q000276:immunology*; D007518:Isoantibodies / Q000627:therapeutic use*; D051379:Mice; D051381:Rats; D018029:Rho(D) Immune Globulin
D007518:Isoantibodies; C061961:RHO(D) antibody; D018029:Rho(D) Immune Globulin