Is it homologous or allogeneic?
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Biomedical subjects
Publications and source records attributed to P L Mollison.
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Two human monoclonal antibodies, one IgG3 and one IgG1, with anti-Rh D specificity, were tested for their ability to clear red cells. Samples of red cells from 12 D-positive subjects were sensitised in vitro with various amounts of antibody, the number of antibody molecules bound to the cells was estimated, and the cells were reinjected into the donor's circulation. Both antibodies mediated clearance but substantially fewer IgG3 than IgG1 antibody molecules were required to produce a given rate of clearance. The IgG3 antibody was slightly more effective than polyclonal anti-D, as judged by comparison with previously published results. Since there is believed to be an association between the rate of red cell clearance by anti-D and the ability of the antibody to suppress D immunisation, the IgG3 monoclonal antibody may prove suitable for the immunoprophylaxis of Rh D haemolytic disease.
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Investigations on six males with naturally occurring Rh antibodies are described. In two subjects in whom the antibody (one anti-E and one anti-D) could be detected only by a two-stage papain technique, the survival of incompatible red cells was normal. In the remaining four subjects, the antibodies (two anti-E and two anti-D) could be detected by the indirect antiglobulin test and, in these, incompatible red cells were destroyed at an accelerated rate; in two of the subjects, 75-99% of the cells were cleared within 24 h; in the other two, 50% of the cells were cleared within 24 h and the remaining cells were cleared far more slowly. All six antibodies were mainly or wholly IgG; a clear-cut immune response was observed in only one case.
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Examination of death certificates and the clinical notes of the patients concerned showed that the number of deaths from rhesus (D) haemolytic disease in England and Wales was 44 and 34 during 1982 and 1983, respectively, a substantial decrease from the figure of 106 for 1977. Of the 78 women whose infants died in 1982 and 1983, 49 had not received anti-Rh immunoglobulin after previous pregnancies with Rh positive infants; most of these deaths would presumably have been prevented had postnatal anti-Rh immunoglobulin been given. In 13 women anti-D was detected during, or immediately after, a first pregnancy, and in 15 women rhesus immunisation developed despite administration of anti-Rh immunoglobulin postnatally. One or two apparent failures of treatment may have been due to underdosage, but it must be concluded that about one third of the deaths in 1982 and 1983 could have been prevented only by giving anti-Rh immunoglobulin antenatally as well as postnatally.
Rh-negative women, immunized to Rh by previous pregnancies, with only low concentrations of IgG anti-Rh(D) in their plasma were assigned at random to test and control groups (7 subjects in each group). Both groups were challenged with an intravenous injection of 0.28 ml of Rh-positive red cells; in addition, the test group received 500 micrograms anti-Rh intramuscularly. 2 weeks after the injections, all subjects showed an increase in plasma anti-Rh concentration; levels in test and control groups were similar. It is concluded that in Rh-immunized subjects with low levels of IgG anti-Rh a secondary response to Rh cannot be prevented by giving passively administered anti-Rh with the red cells.
The response to 0.8 ml of D-positive (ccDEE) red cells injected i.v., together with 1 microgram anti-D i.m., was studied in 13 D-negative male volunteers (test subjects); the red cells were labelled with 51Cr and were found to have a mean survival time of 24 d, after correction for Cr elution. Within the following 5 months, nine of the 13 subjects made anti-D, compared with four out of 12 control subjects in a previous series who received 1 ml of red cells from the same donor but without passively-administered antibody. The time at which anti-D was first detected and the maximum concentration of anti-D attained were similar in test and control subjects. After a second injection of D-positive red cells, given 5 months after the first, the total number of subjects making anti-D became 11 out of 13 in the test series, compared with six out of 12 in the previous control series. Antibody concentrations were similar in test and control subjects. Evidently, Rh immunization was not augmented if this term implies accelerated formation of antibody or an obvious increase in antibody concentration. On the other hand, the suggestive increase in the proportion of responders, though not statistically significant, is consistent with the earlier observations of others and suggests that the effect of a small dose of passively administered antibody is to facilitate primary immunization.
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The immune response to the i.v. injection of 1 ml of D-positive (ccDEE, presumably cDE/cDE) red cells was studied in 12 D-negative (ccddee) subjects who received a simultaneous i.m. injection of 5 microgram anti-D (the test group) and in a further 12 D-negative subjects who were not given anti-D (the control group). In all cases the red cells were labelled with 51Cr. Further injections of 1 ml of red cells were given at 7 and 12 months to subjects who had not made serologically detectable anti-D. In the test group the rate of clearance of the first injection of red cells was very variable, 99% of the cells being cleared in a period ranging from 3 to 20 d. Within 6-10 weeks of the first injection four subjects had produced anti-D; four more subjects produced anti-D after the second injection of red cells. In the control group Cr red cell survival following the first injection was normal in six cases and curtailed in the remaining six. Of the latter, four produced anti-D within 4-10 weeks of the first injection and two produced anti-D only after the second or third injection of red cells. Amongst the subjects who produced anti-D after the first injection of red cells antibody levels were lower in the test group than in the control group, indicating that the injection of 5 microgram of anti-D with 1 ml red cells had not augmented the immune response and might have partially suppressed it.
A comparison was made between the post-transfusion survival of red cells stored in standard ACD-A and in modified ACD-A, containing two-thirds the amount of citrate. Measurements of survival after 28 d storage in both solutions were made in each of six subjects. Mean post-transfusion survival with the two solutions was almost identical. When the results in one subject in whom survival was particularly bad with both solutions were omitted mean values at 24 h were 74.0% for standard ACD-A and 74.9% for modified ACD-A. It is concluded that viability is just as well maintained in modified ACD-A as in standard ACD-A. The results also provide further evidence of large differences between donors with respect to the maintenance of red cell viability during storage.