AT1R-Ab: A New Player in Pediatric Heart Transplant AMR?

Purpose 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. Methods 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 17 positive (ELISA). Results 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). Conclusion 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.