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PLASTIC RECONSTRUCTIVE AND REGENERATIVE SURGERY

Original article

Blood Transfusion - 6 2022 (November-December)

Human neutrophil antigen 3 genotype impacts neutrophil-mediated endothelial cell cytotoxicity in a two-event model of TRALI

Authors

Sara Chiaretti , Mark Burton , Penny Hassel , Filip Radenkovic , Nilam Devikashri , Annette J. Sultana , Fergal T. Temple , Melinda M. Dean , John-Paul Tung

Key words: transfusion-related acute lung injury (TRALI), human neutrophil antigens, neutrophils, lung vascular endothelium
Doi: 10.2450/2022.0013-22
Publication Date: 2022-05-19

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.

References

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Authors

Sara Chiaretti Clinical Services and Research, Australian Red Cross Lifeblood, Brisbane, Queensland, Australia

Mark Burton Transplantation and Immunogenetics Services, Australian Red Cross Lifeblood, Brisbane, Queensland, Australia

Penny Hassel Transplantation and Immunogenetics Services, Australian Red Cross Lifeblood, Brisbane, Queensland, Australia;

Filip Radenkovic Clinical Services and Research, Australian Red Cross Lifeblood, Brisbane, Queensland, Australia; 3Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland, Australia

Nilam Devikashri Transplantation and Immunogenetics Services, Australian Red Cross Lifeblood, Brisbane, Queensland, Australia

Annette J. Sultana Clinical Services and Research, Australian Red Cross Lifeblood, Brisbane, Queensland, Australia; Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia; The Critical Care Research Group, The Prince Charles Hospital, Queensland, Australia

Fergal T. Temple Clinical Services and Research, Australian Red Cross Lifeblood, Brisbane, Queensland, Australia

Melinda M. Dean Clinical Services and Research, Australian Red Cross Lifeblood, Brisbane, Queensland, Australia; The Critical Care Research Group, The Prince Charles Hospital, Queensland, Australia; Faculty of Health, Queensland University of Technology, Brisbane, Queensland, Australia; School of Health and Behavioural Sciences, University of the Sunshine Coast, Queensland, Australia

John-Paul Tung Clinical Services and Research, Australian Red Cross Lifeblood, Brisbane, Queensland, Australia; Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia; The Critical Care Research Group, The Prince Charles Hospital, Queensland, Australia; Faculty of Health, Queensland University of Technology, Brisbane, Queensland, Australia

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