title: 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?
abstract: Anti-D has been widely and effectively used in Rhesus blood group D negative mothers for the prevention of haemolytic disease of the fetus and newborn; its mechanism of action however, often referred to as antibody-mediated immune suppression (AMIS), remains largely unresolved. We investigated, in a murine model, whether active immune suppression or clonal deletion mediated by anti-red blood cell (RBC) immunoglobulin G (IgG) could explain the phenomenon of AMIS. Transfusion of IgG-opsonized foreign RBCs (i.e. AMIS) strongly attenuated antibody responses compared to transfusion of untreated foreign RBCs. When the AMIS-mice were subsequently transfused with untreated RBCs, no immune suppression was observed at 5 and 35 days after AMIS induction; in fact, the mice responded to retransfusion with untreated RBCs in a manner that was characteristic of a secondary immune response. When IgG-opsonized RBCs were transfused concurrently with untreated RBCs, a dose-dependent reduction of the antibody response was observed. This work suggests that the attenuation of the antibody responsiveness by anti-RBC IgG is not associated with active immune suppression or clonal deletion at either the T-cell or B-cell level; rather, the effect appears more characteristic of B-cell unresponsiveness to IgG-opsonized RBCs. These results may have implications for the understanding of the mechanism of action of anti-D in haemolytic disease of the fetus and newborn.
authors.affiliation: Canadian Blood Services, Toronto, ON, Canada.
authors.forename: Davor
authors.initials: D
authors.lastname: Brinc
authors.forename: Hoang
authors.initials: H
authors.lastname: Le-Tien
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Crow
authors.forename: Vinayakumar
authors.initials: V
authors.lastname: Siragam
authors.forename: John
authors.initials: J
authors.lastname: Freedman
authors.forename: Alan H
authors.initials: AH
authors.lastname: Lazarus
mesh_terms: D000818:Animals; D004306:Dose-Response Relationship, Immunologic; D004899:Erythroblastosis, Fetal / Q000517:prevention & control; D017707:Erythrocyte Transfusion; D004912:Erythrocytes / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007074:Immunoglobulin G / Q000276:immunology*; D007075:Immunoglobulin M / Q000096:biosynthesis; D007231:Infant, Newborn; D007518:Isoantibodies / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D018029:Rho(D) Immune Globulin / Q000627:therapeutic use; D012756:Sheep
chemical_list: D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007518:Isoantibodies; D018029:Rho(D) Immune Globulin