Preformed HNA-3a antibodies in renal transplantation: A suggested approach to risk assessment

Patients presenting with a homozygous human neutrophil antigen-3b (HNA-3b)/3b genotype are at risk of HNA-3a alloimmunisation, generating anti-HNA-3a antibodies, which are known to cause severe transfusion-related acute lung injury (TRALI). HNA-3b homozygosity therefore presents a risk of HNA-3a alloimmunisation, and has recently been implicated in antibody-mediated rejection (ABMR) of renal transplants. However, this remains poorly characterised in the literature. Thus, we herein present the first reported case describing the loss of two sequential donor after brainstem death (DBD) renal grafts mediated by HNA-3a antibodies, in the absence of HLA donor-specific antibodies (DSAs) and confirmed by wet crossmatching. In situations involving accelerated graft injury with negative HLA-DSA and positive flow cytometry crossmatching, non-HLA ABMRs should be considered as a possible differential, especially in the context of patients with prior pregnancies, blood transfusions and past transplants as potential sensitisers. Our case demonstrates that virtual crossmatching alone is insufficient in detecting non-HLA antibodies and emphasises the need for a wider repertoire of screening tests beyond this, to enable for enhanced immunosuppression and plasmapheresis.