THERE ARE TWO indications for establishing the clinical significance of red cell (RBCs) alloantibodies in vitro. Rarely, it is to determine whether incompatible RBCs can be given to a patient with a "difficult" antibody. Much more important is the prediction of the severity of hemolytic disease of the newborn (HDN) by establishing the destructive power of the responsible maternal antibodies. Virtually all antibodies that cause HDN are noncomplement-binding IgG antibodies, which destroy RBCs via adherence of sensitized cells to Fc receptors (FcRs) on macrophages. Even IgG anti-A and anti-B, although capable of binding complement, destroy RBCs by this mechanism in the newborn infant.' Two important factors that influence this process cannot be measured in serologic tests (see below). It is for this reason that serologic values, such as the titer of the antibodies in the indirect antiglobulin test (IAT) or the quantity of the antibodies in the maternal serum, do not accurately represent the destructive capacity of the antibody population. Serologic tests have indeed been found to be inadequate to predict the severity of HDN.2-5 Subclasses of IgGAn important characteristic of IgG RBC alloantibodies, which strongly influences their clinical significance, is their subclass. It is well known that the affinity of FcR for IgG4 is very low, and as a consequence, IgG4 antibodies do not affect the RBC life span.6 Abbreviations: ADCC (L) = antibody-dependent cellular cytotoxicity test with lymphocytes as effector cells; ADCC (M) = ADCC (test) with monocytes as effector cells; CL = chemiluminescence (assay); FcR(s) = FC receptor(s); HDN = hemolytic disease of the newborn; IAT = indirect antiglobulin test; MAIMA = monoclonal antibody-specific immobilization of monocyte antigens assay; MMA = monocyte monolayer assay; MoAb(s) = monoclonal antibody(ies); RBC(s) = red cell(s).

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