In vivo immune phagocytosis of neonatal monocytes was significantly correlated to the extent of maternal HLA immunization. Monocytes from all 15 neonates of mothers with HLA antibodies show reduced immune phagocytosis. In contrast, this holds true for monocytes from only 6 out of 13 neonates of mothers without detectable HLA antibodies. We infer the hypothesis that maternal HLA antibodies bind to mononuclear phagocytes of the fetus and of the fetal part of the placenta and thus cause inhibition of immune phagocytosis. Thereby, activation and secondary cell or tissue injury will not ensue and rejection of the fetal allograft is prevented in those pregnancies in which maternal alloimmunization occurs.

900 pregnancy sera were screened for monocyte antibodies. 23 sera (2.6%) were found to be reactive with monocytes in an allotypic pattern distinct from blood group ABO, HLA-A,B,C, DR and DQ specificities. Because of strong reactions and high reproducibility, 4 sera with pure endothelial monocyte (EM) reactivity and 2 sera also positive with B lymphocytes of certain donors were selected for population and family studies. The frequency of positive reactions in a panel of 26 random donors obtaied with the pure EM sera was 13, 8,8 and 13% with clearly distinct patterns. Analysis of the tentatively designated EM antigens 1.1,1.2, 2.1, and 2.2 in 7 families revealed definite segregation with FILA. By means of two crossing-over events within the HLA region the two hypothetical EM loci were localized centromeric of HLA-A and one of both loci centromeric of HLA-B.