HNA-3 antibodies and increased risk of recurrent rejection in kidney transplant recipients.

BACKGROUND

There is an increasing number of biopsies with histological features of antibody mediated rejection but lacking the detection of anti-human leucocyte antigen (HLA) antibodies or C4d deposition. Anti-Human neutrophil antigens-3 (HNA-3) have been reported in severe and fatal cases of Transfusion-Related Acute Lung Injury and Neutropenia Alloimmune Neonatal, a phenomenon mediated by antibody endothelial activation. This study investigated the association between the presence of pre-formed anti-HNA-3 antibodies and the development of a recurrent episode of acute rejection (AR) after kidney transplantation.

METHODS

Patients who experienced the first biopsy confirmed acute rejection (BCAR) between 2011-2019 were screened for the presence of anti-HNA-3 antibodies using pretransplant serum samples. Three techniques were used, Granulocyte Agglutination Test (GAT), Granulocyte Immunofluorescence Test (Flow-GIFT), and microsphere-based technique (LABSCreen Multi kit, One Lambda) to detect and determine the specificity of the antibodies. HNA-3 genotyping of recipients and donors was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). A matched control group included patients with first BCAR but without pretransplant anti-HNA-3 antibodies.

RESULTS

Of 1256 patients with first BCAR, 33 (2.6 %) had anti-HNA-3 antibodies. Compared to the matched control, survival-free of a second BCAR was lower in patients with any anti-HNA-3 antibody (p = 0.014) and in patients with donor specific anti-HNA-3 antibodies (p = 0.015). No differences were observed in histological phenotypes of the rejection episodes comparing patients with and without anti-HNA-3 antibodies.

CONCLUSIONS

This matched cohort study suggests that preformed anti-HNA-3 antibodies are associated with an increased risk of recurrent BCAR. The involved mechanisms remain to be elucidated.