Bacterial contamination of blood components.
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Biomedical subjects
Publications and source records attributed to C P Engelfriet.
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With a view to terminological uniformity, blood group serologists, immunologists and transfusion physicians should refer only to the "ABo' (zero) in stead of the "ABO' system. They also should use "HLA antibodies' in stead of "anti HLA antibodies'. The new Dutch spelling "resus' in stead of "Rhesus' is incorrect from a historical point of view.
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Recent observations have shown that treatment with high-dose intravenous gammaglobulin (IVIgG) given to the mother may improve fetal outcome in cases of severe Rh D alloimmunization. Unfortunately, the costs of this new method of treatment are too high for routine use. Therefore, we decided to apply this treatment to the fetus and to investigate whether the effect of IVIgG might be attributable to blockade of the fetal mononuclear phagocyte system. We have performed a randomized study in which 20 fetuses with severe Rh D-haemolytic disease (HDN) were treated with intrauterine intravascular red cell transfusions (IUT). In 10 of these 20 cases transfusions were followed by administration to the fetus of low-dose IVIgG (85.7 +/- 11.6 mg/kg by ultrasound-estimated fetal weight because of fetal vascular volume considerations). We compared the number of IUTs, postnatal exchange transfusions, haematocrit (Ht) and haemoglobulin (Hb) values before and after transfusion (s) needed by the newborns of the two groups. No significant differences in the transfusion requirements of the fetuses and in the clinical outcome could be demonstrated. However, the 95% confidence interval for the difference in the improvement of cord blood Ht was too wide for any conclusions. The 95% confidence interval for the difference in the improvement of Hb levels suggests that any clinically relevant advantage of IVIgG on Hb is unlikely.
In cases of Rh D alloimmunization, strong results in the antibody-dependent cell-mediated cytotoxicity (ADCC) assay (> 80% lysis as compared to that of the standard anti-D serum) are indicative of severe hemolytic disease to occur in the newborn (HDN). However, discrepant cases were found in which the maternal anti-D gave strong ADCC results and the newborns had no or only mild hemolysis. In the majority of these cases the mother had produced monocyte-reactive IgG alloantibodies, mostly with HLA-DR specificity. Such antibodies may be capable of blocking FcR-mediated functions of the fetal MPS, and it has been postulated that they inhibit destruction of anti-D-sensitized red cells. We here describe 2 families in which such discrepancies were noticed. In 1 family, in spite of ADCC results of > 80%, the Rh D-positive second child was born without signs of hemolysis. However, the Rh D-positive third child suffered from very severe hemolytic disease. The mother had produced monocyte-reactive HLA-DR antibodies in the second pregnancy which, however, did not react with the cells of the third child. In the other family, the severely Rh D-alloimmunized mother had lost her fourth child because of intrauterine death due to HDN. The Rh D-positive fifth child was born with only mild HDN and only in this pregnancy had the mother produced such antibodies. These 2 case histories give further evidence that maternal monocyte-reactive alloantibodies, in both these cases directed against HLA-DR antigens, can protect the Rh D-positive child against hemolytic disease in case of severe Rh D alloimmunization.
IgG present in the circulation of newborn infants is predominantly of maternal origin. In cases of severe Rh D alloimmunization, the maternal anti-D anti-bodies may lead to Rh D-haemolytic disease of the newborn. However, an impaired placental transport of maternal IgG could be associated with the protection of the fetus/newborn against haemolytic disease as shown in this case report.
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The extent to which maternal anti-Rh(D) antibodies support lysis of erythrocytes by monocytes in the antibody-dependent cell-mediated cytotoxicity (ADCC) assay is closely correlated with the severity of Rh(D) haemolytic disease of the newborn infant (HDN). However, in some cases HDN is much milder than would be predicted from the ADCC value. We postulated that maternal ADCC-blocking alloantibodies against paternal antigens on monocytes can protect these infants against severe haemolysis. We studied 13 severely Rh(D)-alloimmunised mothers whose infants showed unexpectedly mild HDN (group I) and 14 women with similar ADCC values but whose infants had severe HDN (group II). 7 group-I women had monocyte-reactive IgG alloantibodies that inhibited lysis by paternal monocytes in the ADCC. No such antibodies were found in group II (p less than 0.01). In 6 of the 7 serum samples with monocyte-reactive antibodies, the antibodies had HLA-DR specificity. Our findings suggest that Rh(D)-positive children of some severely Rh(D)-alloimmunised women may be protected from severe HDN by maternal non-HLA-class-I, IgG alloantibodies against paternal monocyte blood-group antigens. These antibodies may inhibit the mononuclear phagocyte system of the fetus.
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