Human neutrophil antigen 3 genotype impacts neutrophil-mediated endothelial cell cytotoxicity in a two-event model of TRALI.
Blood Transfus
; 20(6): 465-474, 2022 11.
Article
em En
| MEDLINE
| ID: mdl-35848624
ABSTRACT
BACKGROUND:
Antibodies against human neutrophil antigen (HNA)-3a are associated with severe cases of transfusion-related acute lung injury (TRALI). The HNA-3 system is located on choline transporter-like 2 (CTL-2) protein. CTL-2 is encoded by the gene SLC44A2 and a single-nucleotide polymorphism c.461G>A results in two antigens HNA-3a and HNA-3b. Three HNA-3 genotypes/ phenotypes exist HNA-3aa, HNA-3bb, and HNA-3ab. Two different pathways of anti-HNA-3a TRALI have been described a two-hit neutrophil-dependent pathway and a one-hit neutrophil-independent pathway. However, it is not clear whether HNA-3ab heterozygous patients have a lower risk of anti-HNA-3a-mediated TRALI compared to HNA-3aa homozygous patients. MATERIALS ANDMETHODS:
Healthy volunteers were genotyped for HNA-3 by real-time polymerase chain reaction, and phenotyped for HNA-3a by granulocyte immunofluorescence test (GIFT) and granulocyte agglutination test (GAT) against two donor sera containing anti-HNA-3a antibodies. The two sera were also used in in vitro models of human pulmonary microvascular endothelial cell (HLMVEC) cytotoxicity to investigate pathways of TRALI development.RESULTS:
For both anti-HNA-3a sera, GIFT results matched the genotype, with a lower GIFT ratio for HNA-3ab neutrophils compared to HNA-3aa neutrophils, whereas GAT results showed no difference in agglutination. HLMVEC cytotoxicity was not observed in a one-hit neutrophil-independent model but was observed in a two-hit neutrophil-dependent model. Differences in cytotoxicity were observed between the two anti-HNA-3a sera used. Consistent with reduced HNA-3a antigen density as measured by GIFT, HNA-3ab neutrophils mediated less HLMVEC cytotoxicity than HNA-3aa neutrophils.CONCLUSION:
HNA-3 genotype and HNA-3a antigen expression impacted the severity of anti-HNA-3a-mediated HLMVEC cytotoxicity in a two-hit neutrophil-dependent model of TRALI. Different HNA-3a antibodies might also impact the magnitude of HLMVEC cytotoxicity.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Lesão Pulmonar Aguda Relacionada à Transfusão
/
Neutrófilos
Limite:
Humans
Idioma:
En
Revista:
Blood Transfus
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Austrália