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Characterization of a new alloantigen (SH) on the human neutrophil Fc gamma
receptor IIIb
J Bux, EL Stein, P Bierling, P Fromont, M Clay, D Stroncek and S Santoso
Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig
University, Giessen, Germany.
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.
Volume 89,
Issue 3,
pp. 1027-1034,
02/01/1997
Copyright © 1997 by The American Society of Hematology
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