Abstract
<h3>Purpose</h3> Angiotensin II type 1 receptor antibodies (AT1R-Ab) are associated with non-human leukocyte antigen (HLA) mediated antibody mediated rejection (AMR) and graft failure in adult renal transplantation. They can be stimulated by ventricular assist device (VAD) support, but data regarding AT1R-Ab in pediatric heart transplantation (HT) are scarce. The purpose of this study is to describe the incidence of non-HLA mediated AMR and identification of AT1R-Ab in a pediatric HT cohort. <h3>Methods</h3> We performed a single-center retrospective review of children who underwent primary HT from July 2016 to July 2020. AMR was defined by the presence of complement deposition (+C4d) on heart biopsy. Non-HLA mediated AMR was defined by the absence of donor-specific HLA antibodies (HLA-DSA). AT1R-Ab testing was defined as < 10 negative, 10-17 borderline, and > 17 positive (ELISA). <h3>Results</h3> There were 100 patients who underwent primary HT during the study period (median age 4.5 years). There were 19 episodes of AMR in 17 patients. HLA-DSA were present in 12 episodes (63%) and absent in 7 (37%) episodes. Non-HLA mediated AMR occurred earlier post-HT compared to AMR with HLA-DSA (median 7 days vs 244 days, p = 0.04). Four patients with AMR in the absence of HLA-DSA were tested for AT1R-Ab; 3 were positive and 1 was borderline. Of the 3 patients with positive AT1R-Ab, 2 were previously supported on VAD, 2 had symptomatic AMR, 2 subsequently received losartan, and none have had recurrence of AMR (Table). <h3>Conclusion</h3> Non-HLA mediated AMR accounted for 37% of AMR episodes and occurred earlier post-HT compared to AMR with HLA-DSA in a single-center cohort. AT1R-Ab were present in 3 of 4 patients with non-HLA mediated AMR in whom AT1R-Ab testing was performed. In light of the recent data regarding AT1R-Ab in renal transplantation, investigation of the prevalence and clinical significance of AT1R-Ab in pediatric HT, particularly in early non-HLA mediated AMR and in those bridged to HT with VAD, is warranted.
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