Journal article
Human neutrophil antigen 3 genotype impacts neutrophil-mediated endothelial cell cytotoxicity in a two-event model of TRALI
Blood Transfusion , Vol.20(6), pp.465-474
2022
PMCID: PMC9726621
PMID: 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 and methods - 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.
Details
- Title
- Human neutrophil antigen 3 genotype impacts neutrophil-mediated endothelial cell cytotoxicity in a two-event model of TRALI
- Authors
- Sara Chiaretti (Author) - Australian Red Cross LifebloodMark Burton (Author) - Australian Red Cross Blood ServicePenny Hassel (Author) - Australian Red Cross Blood ServiceFilip Radenkovic (Author) - The University of QueenslandNilam Devikashri (Author) - Australian Red Cross Blood ServiceAnnette J Sultana (Author) - The University of QueenslandFergal T Temple (Author) - Australian Red Cross Blood ServiceMelinda M Dean (Author) - University of the Sunshine Coast, Queensland, School of Health and Behavioural Sciences - LegacyJohn-Paul Tung (Author) - Australian Red Cross Lifeblood
- Publication details
- Blood Transfusion , Vol.20(6), pp.465-474
- Publisher
- S I M T I Servizi srl
- Date published
- 2022
- DOI
- 10.2450/2022.0013-22
- ISSN
- 2385-2070
- PMID
- 35848624; PMC9726621
- Organisation Unit
- School of Health - Biomedicine; School of Health and Behavioural Sciences - Legacy
- Language
- English
- Record Identifier
- 99697897302621
- Output Type
- Journal article
Metrics
56 Record Views
InCites Highlights
These are selected metrics from InCites Benchmarking & Analytics tool, related to this output
- Collaboration types
- Domestic collaboration
- Web Of Science research areas
- Hematology
UN Sustainable Development Goals (SDGs)
This output has contributed to the advancement of the following goals:
Source: SDGs from InCites