Do monocyte ADCC assays accurately predict the severity of hemolytic disease of the newborn caused by antibodies to high-frequency antigens?

Monocyte ADCC assays are helpful indicators of the severity of hemolytic disease of the newborn (HDN) due to anti-D. It would be particularly useful if the assays also accurately predicted the ability of antibodies to high-frequency antigens (UFA) to cause HDN. To investigate this possibility, 14 antenatal sera containing antibodies to HFA were tested and the results correlated with the severity of HDN. Antibody titers were determined using an indirect antiglobulin test (IAT). Eight sera (anti-Hy, -Di^b, -Jr^a -ScI, -In^b, -Wr^b, and-U [n =2]) had low ADCC activity (< 28%) and did not cause HDN. The IAT titers ranged from 4 to 128. Two antibodies (anti-Ena and anti-Rh29) had high ADCC activity (≥ 72%) and high IAT titers (≥ 1,024), and both caused severe HDN. The remaining four antibodies (anti-Cr^a, -In^b, and -U [n = 2]) had ADCC activity ≥ 40 percent and titers ≥ 128, but they did not cause HDN. The inability of anti-Cr^a and anti-In^b to cause HDN is presumed to be related to fetal antigen expression and tissue distribution. The anti-In^b was further investigated using monocyte binding and inhibition studies. The absence of HDN in the presence of potent anti-U remains unexplained. In general, antibodies with low ADCC activity do not cause HDN, but high ADCC activity does not always indicate severe HDN. Immunohematology 1996;12:20-26.