Assuntos
Púrpura/diagnóstico , Púrpura/etiologia , Corticosteroides/uso terapêutico , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Imunoglobulinas Intravenosas , Contagem de Plaquetas , Transfusão de Plaquetas , Complicações Pós-Operatórias , Púrpura/sangue , Púrpura/tratamento farmacológico , Púrpura Trombocitopênica/diagnóstico , Reação TransfusionalRESUMO
BACKGROUND: People with the human neutrophil antigen (HNA)-3b/3b type can make HNA-3a antibodies, which have been reported to cause immune neutropenia disorders and are especially prone to cause severe cases of transfusion-related acute lung injury. However, knowledge of HNA-3 allele frequencies outside Caucasian populations is limited. We developed a high-throughput genotyping assay and determined the HNA-3a/3b genotype frequencies in six different racial and ethnic groups. STUDY DESIGN AND METHODS: Genotyping utilized TaqMan 5' exonuclease chemistry and real-time polymerase chain reaction. A total of 742 DNA samples from six different racial and ethnic groups were genotyped for HNA-3a and HNA-3b. RESULTS: The genotyping assay showed 100% sensitivity and specificity compared to sequencing and phenotyping and had high throughput. A significant percentage of Caucasians (6.5%), Han Chinese (16%), and Asian Indians (6%) typed HNA-3b/3b, but only a small percentage of Hispanics (1%) and no African or Native Americans. CONCLUSIONS: The HNA-3 genotyping assay had high sensitivity, specificity, and sample throughput. HNA-3b/b genotype results determined for 742 individuals representing six different racial and ethnic groups showed that there could be a significant risk of producing anti-HNA-3a in Chinese, as well as in Caucasian and Asian Indian blood donor populations, but a very low risk in Hispanic, African, or Native American populations.
Assuntos
Incompatibilidade de Grupos Sanguíneos/etnologia , Incompatibilidade de Grupos Sanguíneos/genética , Isoantígenos/genética , Glicoproteínas de Membrana/genética , Proteínas de Membrana Transportadoras/genética , Neutropenia/etnologia , Neutropenia/genética , Lesão Pulmonar Aguda/etnologia , Lesão Pulmonar Aguda/genética , Negro ou Afro-Americano/genética , Negro ou Afro-Americano/estatística & dados numéricos , Asiático/genética , Asiático/estatística & dados numéricos , Etnicidade/genética , Etnicidade/estatística & dados numéricos , Predisposição Genética para Doença/etnologia , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala , Hispânico ou Latino/genética , Hispânico ou Latino/estatística & dados numéricos , Humanos , Indígenas Norte-Americanos/genética , Indígenas Norte-Americanos/estatística & dados numéricos , Isoantígenos/imunologia , Glicoproteínas de Membrana/imunologia , Proteínas de Membrana Transportadoras/imunologia , Fosfodiesterase I/genética , Fatores de Risco , Sensibilidade e Especificidade , População Branca/genética , População Branca/estatística & dados numéricosRESUMO
The molecular basis of the HNA-3a/b (5b/a) leukocyte antigen system has not yet been defined despite evidence that HNA-3a-specific antibodies are particularly prone to cause severe, often fatal, transfusion-related lung injury. We used genome-wide single nucleotide polymorphism scanning and sequencing of DNA from persons of different HNA-3a/b phenotypes to identify a single single nucleotide polymorphism in exon 7 of the CLT2 gene (SLC44A2) that predicts an amino acid substitution in the first extracellular loop of choline transporter-like protein 2, a member of the choline transporter-like protein family of membrane glycoproteins, and correlates perfectly with HNA-3a/b phenotypes (R154 encodes HNA-3a; Q154 encodes HNA-3b). Mass spectrometric analysis of proteins immunoprecipitated from leukocytes by anti-HNA-3a provided direct evidence that anti-HNA-3a recognizes choline transporter-like protein 2. These findings will enable large-scale genotyping for HNA-3a/b to identify blood donors at risk to have HNA-3a-specific antibodies and should facilitate development of practical methods to detect such antibodies and prevent transfusion-related lung injury.