Suppression of Primary Rh Immunization by Passively-Administered Antibody. Experiments in Volunteers

Abstract

Rh-negative volunteers were given an injection of 1 ml of Rh-positive red cells, either alone or with 15 μg or 75 μg anti-D. Six months later anti-Rh was detected in 2 out of 14 subjects who had originally received Rh-positive red cells alone but in none out of 8 subjects who had also received 15 μg anti-D and in none out of 15 subjects who had also received 75 μg anti-D. Six months after the start of the experiment, thirty-four of the subjects were injected with 1 ml of ^51Cr labelled red cells without anti-D. At 7—11 days after injection, survival was normal in all of 13 subjects who had received 75 μg anti-D with their first injection of red cells. By contrast, survival was subnormal in seven out of 13 cases who had received no anti-D with their first injection of red cells. This difference is significant (p = 0.027) and is taken to indicate that primary immunization occurred when 1 ml of Rh-positive red cells was given alone but was prevented when 1 ml of red cells was given with 75 μg anti-D. Survival at 7 days was slightly subnormal in 2 out of 8 subjects who had received 15 μg anti-D with their first injection of red cells; this is taken as evidence that no augmentation of primary immunization was produced with this dose. In a follow-up study of another series of Rh-negative volunteers, who had been injected with 0.3 ml of Rh-positive red cells at a time when they had between 0.6 and 4 fig anti-D in their circulation, 3 to 8 months later the survival of injected Rh-positive red cells was normal in 5 out of 6 cases, suggesting that there had been no augmentation of primary immunization.

Prevention of Maternal Rh Immunization after Accidental Transfusion of D(Rh(0))-positive Blood

“…The mean assayed antibody concentration per ml in the five separate lots of Rh immunoglobulin fortunately was 342 figjra\, being greater than anticipated. The above dosimetry is comparable with that in another preliminary study [22] where approximately 42 fig of anti-Rh antibodies per ml of D-positive red cells was shown to yield good primary immunosuppression when 7-9 ml of D-incompatible red cells were administered. This dose is also closely compatible with the amount of Rh immunoglobulin suggested for suppres sion of Rh sensitization at another conference [31].…”

“…Finally, the selected dosage should both elicit prompt immune clearance of the foreign D-positive red cell population and show a sufficient amount of circulating antibody after their elimination [26,32], as the latter may prevent Rh sensitization by a negative feedback mechanism [30,32]. While the rate of immune clearance of the D-positive segment of the erythron by anti-D antibodies is not the primary factor in preventing Rh immuniza tion, individuals given lesser amounts of Rh immunoglobulin who ex hibited delayed regression curves appear more susceptible to sensitization [22] As only 30 ml of this preparation (of varied lots) of Rh immunoglobulin could be obtained for this emergency, this also was the final dose used. The mean assayed antibody concentration per ml in the five separate lots of Rh immunoglobulin fortunately was 342 figjra\, being greater than anticipated.…”

“…However, Mollison et al [22] concluded that 75 fig of anti-D antibodies inhibited primary immunization by 1.0 ml of D-positive red cells, which were also of Rh group CDe/ce (Rhxrh), as administered to Mrs. C.X.…”

The Structure and Function of the Rh Antigen Complex

“…By the 1960's, a mere 20 years after the discovery of Rh incompatibility, HDN due to anti-D could be effectively prevented. 2,3 The Rh system has long been known to be one of the most complex blood group systems. In addition to the presence or absence of the D antigen, other common Rh antigens include the allelic C or c, and E or e. However, over fifty different Rh antigens have been identified by investigating the specificity of antibodies produced after blood transfusion or pregnancy.…”

Human Monoclonal Anti-D-Induced Clearance of Human D-Positive Red Cells in a Chimpanzee Model

“…The rate of red cell destruction in vivo caused by anti bodies depends on the number of antibody molecules at tached to red cells [9], Thus, the rate of destruction brought about by a particular antibody depends on its concentration and on the average value of its equilibrium constant. To estimate the amount of antibody molecules bound per RBC we measured the dissociation constant of each mAb and calculated the concentration of available antibodies from the volume of the vascular plasma sector and the quantitiy of antibodies injected to the animals.…”