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.
Shepard
S L
SL
International Blood Group Reference Laboratory, Bristol, UK.
Noble
A L
AL
Filbey
D
D
Hadley
A G
AG
D019138:Antibodies, Blocking / Q000627:therapeutic use*; D004899:Erythroblastosis, Fetal / Q000628:therapy*; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008163:Luminescent Measurements; D008165:Luminol; D009000:Monocytes / Q000276:immunology*; D010587:Phagocytosis; D011247:Pregnancy; D017452:Receptors, IgG / Q000276:immunology*; D012204:Rh-Hr Blood-Group System / Q000737:chemistry*; D012680:Sensitivity and Specificity
D019138:Antibodies, Blocking; D017452:Receptors, IgG; D012204:Rh-Hr Blood-Group System; C026410:Rho(D) antigen; D008165:Luminol