Evidence for the Protective Effect of Maternal FcR‐Blocking IgG Alloantibodies HLA‐DR in Rh D‐Haemolytic Disease of the Newborn

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Abstract
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 alloimmunizatio