Lessons learnt from many years of experience using anti-D in humans for prevention of RhD immunization and haemolytic disease of the fetus and newborn

Although the exact mechanism of suppression of D immunization by administration of passive IgG anti-D remains to be elucidated, it is known that D-positive red cells are rapidly cleared to the spleen by macrophages via IgG Fc receptor (FcγR) interactions and rendered non-immunogenic. Indeed, to ensure prophylactic anti-D is likely to be effective at preventing D immunization to a large FMH, women are tested 2–3 days later to check that fetal cells are cleared from the circulation. Otherwise, allogeneic red cells have a long survival after FMH or transfusion. Alloimmune responses are slow to develop, typically 5–15 weeks for anti-D. This is probably due to their lack of danger signals (from foreign molecules) so that they are not recognized by the immune system until they become senescent, which then stimulates their phagocytosis via phosphatidyl serine receptors. Without RhD prophylaxis, approximately 17% of D-negative women become immunized after pregnancy with a D-positive fetus. This incidence is lower than for deliberately immunized normal subjects (up to approximately 85% respond because for most women the volumes of FMH are too small for the red cells to be immunogenic. Pregnant women can make robust alloimmune responses whilst tolerating their semi-allogeneic fetus.

Lessons learnt from many years of experience using anti-D in humans for prevention of RhD immunization and haemolytic disease of the fetus and newborn

The “Rh Disease” Explained