Premium
Geno‐ and phenotyping and immunogenicity of HNA‐3
Author(s) -
Reil Angelika,
Wesche Jan,
Greinacher Andreas,
Bux Juergen
Publication year - 2011
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/j.1537-2995.2010.02751.x
Subject(s) - genotyping , immunogenicity , immunology , antibody , biology , allele , population , polymerase chain reaction , genotype , gene , medicine , genetics , environmental health
BACKGROUND: Alloantibodies directed against the human neutrophil alloantigen (HNA)‐3a are frequently implicated in severe and fatal transfusion‐related acute lung injury (TRALI). The HNA‐3a/3b system results from a single‐nucleotide exchange (461G>A; Arg154Gln) in the choline transporter‐like protein 2 gene. Genotyping may allow identification of blood donors at risk to develop HNA‐3a antibodies. STUDY DESIGN AND METHODS: A polymerase chain reaction using sequence‐specific primers (PCR‐SSP) for genotyping of HNA‐3a and ‐3b alleles was designed. Results of genotyping and phenotyping were compared in 40 randomly selected individuals and in blood donors and recipients of six TRALI cases associated with HNA‐3a antibodies. Phenotyping was performed by granulocyte immunofluorescence and granulocyte agglutination using typing sera for HNA‐3a and two recently found HNA‐3b–reactive sera. Immunogenicity of HNA‐3a was determined by the rate of HNA‐3a alloantibodies in HNA‐3b homozygous parous women. RESULTS: Genotyping and phenotyping results correlated to 100% and were in accordance with alloantibody formation and binding in HNA‐3a antibody associated TRALI cases. Gene frequencies of HNA‐3a and ‐3b were 0.792 and 0.207 in the German population with 64.1% homozygous individuals for the HNA‐3a allele, 5.5% for the HNA‐3b allele, and 30.4% heterozygous individuals, in accordance with the Hardy‐Weinberg equilibrium and the gene frequencies of 0.819 and 0.181 reported in 1964. Immunization rates were estimated to be of 7% for HNA‐3a and 0.5% for HNA‐3b. CONCLUSION: The PCR‐SSP method allows reliable determination of the HNA‐3a and ‐3b genotypes; approximately 7% of HNA‐3b homozygous women develop antibodies when exposed to the HNA‐3a antigen during pregnancy.