Inhibition of the monocyte chemiluminescent response to anti-D-sensitized red cells by Fc gamma RI-blocking antibodies which ameliorate the severity of haemolytic disease of the newborn.

Luminol-enhanced chemiluminescence (CL) may be used to measure the metabolic response of human monocytes to red cells sensitized by anti-D. The functional activity of maternal anti-D when measured in this way correlates with the severity of haemolytic disease of the newborn (HDN) in D-positive fetuses. Occasionally, however, women with levels of functionally active anti-D predictive of moderate to severe HDN may deliver D-positive babies with unexpectedly mild disease. In the current study we have shown that serum from 12 of 15 such women contained monocyte-binding IgG antibodies which blocked Fc gamma RI and inhibited the CL response of monocytes to red cells sensitized with monoclonal anti-D. In contrast, Fc gamma RI-blocking antibodies were found in the serum from only 4 of 11 women who were matched for anti-D activity but who delivered babies with severe HDN (p < 0.05). Antibodies responsible for inhibition of CL responses were predominantly against HLA class I antigens. The CL response of monocytes to sensitized red cells was at least as sensitive to inhibition by Fc gamma RI-blocking antibodies as were phagocytic and lytic responses. Our data suggest that inhibition of the CL test is an objective, sensitive and relatively simple technique for detecting and investigating Fc gamma RI-blocking antibodies which may ameliorate the severity of HDN.

Predicting the severity of haemolytic disease of the newborn: an assessment of the clinical usefulness of the chemiluminescence test.

The ability of the chemiluminescence test (CLT) to predict the severity of haemolytic disease of the newborn (HDN) was determined in 80 alloimmunized pregnant women who delivered antigen-positive babies. In 54 cases of alloimmunization to D, results from the CLT showed better correlation with fetal outcome than anti-D concentration measured by AutoAnalyzer (r = 0.70 and 0.36 respectively). Results from the CLT permitted a threshold level of antibody activity (30%) below which 15/20 babies were unaffected or had mild disease, and only one required transfusion therapy in utero. CLT results above 30% were associated with moderate or severe disease in all cases. Results from the AutoAnalyzer proved a less reliable predictor of disease severity; three women with anti-D levels > 20 iu/ml delivered unaffected babies, and two women with anti-D levels < 10 iu/ml delivered babies who had required transfusion in utero. The clinical usefulness of the CLT derives from the possibility of avoiding invasive monitoring procedures in women with high levels of anti-D which is relatively non-functional.