Characterization of a new alloantigen (SH) on the human neutrophil Fc gamma receptor IIIb.
Polymorphic structures of the neutrophil Fc gamma receptor IIIb (Fc gamma RIIIb) result in alloantibody formation that causes alloimmune neonatal neutropenia and transfusion reactions. Alloantigens located on Fc gamma RIIIb include the antigens NA1 and NA2. In four cases of alloimmune neonatal neutropenia, granulocyte-specific alloantibodies directed against a thus far unknown antigen were detected by granulocyte agglutination and immunofluorescence tests in the maternal sera. By the use of the monoclonal antibody-specific immobilization of granulocyte antigens (MAIGA) assay, the new antigen, termed SH, was located on the Fc gamma RIIIb. Nucleotide sequence analysis of the Fc gamma RIIIb coding region from a SH(+) individual showed a single-base C-->A mutation at position 266, which results in an Ala78Asp amino acid substitution. A family study confirmed that this nucleotide difference is inherited, and corresponds to the SH phenotype. Serologic typing of 309 randomly selected individuals showed an antigen frequency of 5% in the white population. The same frequency was found by genotyping, for which a technique based on polymerase chain reaction (PCR) using sequence-specific primers (PCR-SSP) was developed. Typing of all SH(+) individuals for NA1 and NA2, and PCR-restriction fragment length polymorphism analysis of the NA-specific PCR products from five SH(+) individuals using the SH-specific endonuclease SfaN 1 showed that SH antigen is very probably the result of an additional mutational event in the NA2 form of the Fc gamma RIIIB gene. Immunochemical studies also demonstrated that the SH determinants reside on the 65- to 80-kD NA2 isoform of the Fc gamma RIIIb. Our findings show the existence of an additional polymorphism of the Fc gamma RIIIb, which can result in alloantibody formation causing alloimmune neonatal neutropenia.
Bux
J
J
Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen, Germany.
Stein
E L
EL
Bierling
P
P
Fromont
P
P
Clay
M
M
Stroncek
D
D
Santoso
S
S
D000328:Adult; D001787:Blood Group Incompatibility / Q000235:genetics / Q000276:immunology; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007518:Isoantibodies / Q000737:chemistry; D007519:Isoantigens / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D009503:Neutropenia / Q000235:genetics / Q000276:immunology; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012333:RNA, Messenger / Q000032:analysis; D017452:Receptors, IgG / Q000737:chemistry* / Q000235:genetics / Q000276:immunology
D007518:Isoantibodies; D007519:Isoantigens; D012333:RNA, Messenger; D017452:Receptors, IgG; C072753:neutrophil-specific antigen NA2; C104384:neutrophil-specific antigen SH