CHARACTERIZATION OF A NEW ALLOANTIGEN (SH) ON THE HUMAN NEUTROPHIL FC-GAMMA-RECEPTOR IIIB

Polymorphic structures of the neutrophil Fc gamma receptor IIIb (Fc ga mma RIIIb) result in alloantibody formation that causes alloimmune neo natal neutropenia and transfusion reactions. Alloantigens located on F c gamma RIIIb include the antigens NA1 and NA2. In four cases of alloi mmune neonatal neutropenia, granulocyte-specific alloantibodies direct ed against a thus far unknown antigen were detected by granulocyte agg lutination and immunofluorescence tests in the maternal sera. By the u se of the monoclonal antibody-specific immobilization of granulocyte a ntigens (MAIGA) assay, the new antigen, termed SH, was located on the Fc gamma RIIIb. Nucleotide sequence analysis of the Fc gamma RIIIb cod ing region from a SH(+) individual showed a single-base C-->A mutation at position 266, which results in an Ata(76)Asp amino acid substituti on. A family study confirmed that this nucleotide difference is inheri ted, and corresponds to the SH phenotype. Serologic typing of 309 rand omly selected individuals showed an antigen frequency of 5% in the whi te population. The same frequency was found by genotyping, for which a technique based on polymerase chain reaction (PCR) using sequence-spe cific primers (PCR-SSP) was developed, Typing of all SH(+) individuals for NA1 and NA2, and PCR-restriction fragment length polymorphism ana lysis of the NA-specific PCR products from five SH(+) individuals usin g the SH-specific endonuclease SfaN I showed that SH antigen is very p robably the result of an additional mutational event in the NA2 form o f the Fc gamma RIIIB gene. Immunochemical studies also demonstrated th at the SH determinants reside on the 65- to 80-kD NA2 isoform of the F c gamma RIIIb. Our findings show the existence of an additional polymo rphism of the Fc gamma RIIIb, which can result in alloantibody formati on causing alloimmune neonatal neutropenia. (C) 1997 by The American S ociety of Hematology.