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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.

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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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