ALLOIMMUNE NEONATAL NEUTROPENIA RESULTING FROM IMMUNIZATION TO A HIGH-FREQUENCY ANTIGEN ON THE GRANULOCYTE FC-GAMMA RECEPTOR-III

Background: Alloimmune neonatal neutropenia is mainly caused by NA- or NB1-specific alloantibodies. An antibody in the serum of a Turkish mo ther who had given birth to an infant with alloimmune neonatal neutrop enia showed no NA or NB specificity and was therefore investigated fur ther. Study Design and Methods: The number of antibody-binding sites w as calculated by determination of elutable IgG from granulocytes using a quantitative sandwich enzyme-linked immunosorbent assay. Complement activation was tested by immunofluorescence (C3d) and cytotoxicity te sts. The antigen was identified using the antigen-capture assay, monoc lonal antibody-specific immobilization of granulocyte antigens, and a modified immunoprecipitation method based upon biotinylation of protei ns and visualization by luminescence (luminoimmunoprecipitation). Fami ly study and determination of antigen frequency were done by Immunoflu orescence ana agglutination tests. Results: A noncytotoxic, granulocyt e-specific alloantibody that recognized the Fc gamma receptor III, ind ependent of the NA phenotype, was detected, and 242,000 binding sites per cell were calculated. Of granulocytes from 150 randomly selected G erman blood donors, the alloantibody bound to all. The maternal cells were typed NA1/NA2-and NB1-positive. Conclusion: These data reveal the presence of a previously unrecognized, high frequency epitope on the granulocyte Fc gamma receptor III. Luminoimmunoprecipitation proved to be a simple, nonradioactive technique that was useful in identifying the molecule involved.