Circulatory clearance of transfused antibody-sensitized red cells in an entirely allogenic rabbit model.

Abstract

Antibodies against histocompatibility antigens on phagocytes abrogate their Fc gamma-receptor-mediated functions in vitro. Studies were carried out to determine whether this phenomenon also exists in vivo. An allogenic blood group antibody was generated in rabbits. Red cells sensitized with this antibody were internalized in vitro by rabbit phagocytes. Another allogenic antibody specific for major histocompatibility complex (MHC) antigens of rabbits was produced. Plasma containing this antibody was infused into rabbits with phagocytes expressing the corresponding MHC antigens. Thereafter, the sensitized rabbit red blood cells were transfused into the rabbits. The following 3 phases of the circulatory clearance of transfused sensitized red cells could be observed when MHC antibodies were not given prior to the transfusion: 1. initial rapid clearance of the cells (t/2 = 1.7-3.3 min), 2. release of the cells back into the circulation after 0.5-24 h and 3. terminal slow clearance which was, however, faster than that with unsensitized cells. Two independent experiments carried out on the same recipient out of the 3 recipients analysed showed that the prior treatment of the recipient with MHC-alloantibodies extended the circulatory half-life of the sensitized red cells during the terminal phase from t/2 = 1 day to t/2 = 3 and 4 days, respectively. Antibodies against MHC antigens on phagocytes can reduce the Fc gamma-receptor-mediated immune elimination of sensitized red cells. This corresponds to the observation that many cases of morbus haemolyticus neonatorum show unexpectedly reduced levels of foetal red cell destruction and a good clinical outcome if mothers not only produce antibodies to Rh (D) but also to foetal MHC antigens.