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Limited potential of sheep as a large animal to model transfusion-related acute lung injury mediated by antibodies against human neutrophil antigen 3a
Journal article   Open access   Peer reviewed

Limited potential of sheep as a large animal to model transfusion-related acute lung injury mediated by antibodies against human neutrophil antigen 3a

Filip Radenkovic, Mark Burton, Penny Hassell, Sara Chiaretti, Xuan Bui, Shen Zhao, Martina Jones, Robert Flower and John-Paul Tung
Annals of Blood, Vol.9, pp.1-9
2024
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Published VersionCC BY-NC-ND V4.0 Open Access

Abstract

immunology transfusion granulocyte human neutrophil antigen (HNA)
Transfusion-related acute lung injury (TRALI) is a potentially life-threatening adverse transfusion reaction. Many severe cases of TRALI relate to transfusion of antibodies against human neutrophil antigen 3 (HNA-3). Characterization of the HNA-3 antigen on choline transporter-like protein 2 (CTL2) led to the discovery that human anti-HNA-3a alloantibodies show some cross-reactivity with mouse CTL2. This suggested that human anti-HNA-3a antibodies may react with CTL2 from other species. Although small rodent models are crucial for scientific research, their clinical relevance may be limited due to differences in physiology and, as a result, findings obtained from murine models may not be directly applicable to clinical settings. Sheep have previously been used to model non-antibody mediated TRALI and were therefore assessed for their potential to model for anti-HNA-3a mediated TRALI. Sequences for CTL2 and the gene that encodes it (SLC44A2) from humans, mice, and sheep were compared using publically available databases. Binding experiments were performed with human sera containing an anti-HNA-3a antibody and human, mouse and sheep cells. Although analysis showed that sheep SLC44A2 and CTL2 shared high homology with both human and mouse counterparts (88–89% gene homology, 95–96% protein homology), including the Arg154 residue responsible the HNA-3a variant, no significant anti-HNA-3a alloantibody binding was observed with sheep cells. Therefore, this study suggests that sheep would not be a suitable large animal in which to model TRALI mediated by human anti-HNA-3a antibodies.

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