Inhibition of the Monocyte Chemiluminescent Response to Anti-D- Sensitized Red Cells by FcγRI-Blocking Antibodies Which Ameliorate the Severity of Haemolytic Disease of the Newborn

Abstract

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 FcγRI and inhibited the CL response of moncytes to red cells sensitized with monoclonal anti-D. In contrast, FcγRl-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 FcγRl- 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 FcγRl-blocking antibodies which may ameliorate the severity of HDN.

Functions of the Fc receptors for immunoglobulin G

“…2 and 3). This hypothesis was independently confirmed in studies on mothers and their newborns with HDN (138,139). Our group came to the same conclusion in a multicenter study on more individuals without, in contrast to Dooren et al (138) and Shepard et al (139), selecting the cases by immunological criteria of the causative Rhesus antibodies.…”

“…Our group came to the same conclusion in a multicenter study on more individuals without, in contrast to Dooren et al (138) and Shepard et al (139), selecting the cases by immunological criteria of the causative Rhesus antibodies. Contrary to the findings of Dorren et al (138) and in agreement with those of Shepard et al (139), we found that the ameliorating antibodies were primarily specific for HLA A, B, and C (140). Maternal HLA antibodies also could be protective against other detrimental antibodies of the mother, e.g., to fetal platelet antigens causing the fetal or neonatal alloimmune thrombocytopenia or passive autoimmune thrombocytopenia, and to neutrophil granulocyte antigens causing the respective alloimmune neutropenia of the child.…”