Association between Pretransplant Antibody against Angiotensin II Type 1 Receptor and Posttransplant Allograft Injury

M. Philogene, A. B. Massie, H. Kong, Pali Dedhiya Shah, A. Cochrane, I. Ponor, D. Levine, K. B. Shah, S. Hsu, E. D. Feller, M. E. Rodrigo, S. S. Najjar, I. Tunc, G. Berry, C. Marboe, M. Jang, S. Agbor-Enoh, H. Valantine

Research output: Contribution to journalArticlepeer-review

Abstract

PURPOSE: In heart transplantation (HT), antibodies directed against Angiotensin II type 1 receptor (AT1RAb) have been associated with antibody-mediated rejection (AMR), acute cellular rejection (ACR), and microvasculopathy. The effect of AT1RAb detected pre-HT on immediate post-HT allograft injury remains poorly defined. In this study, we leverage a validated and sensitive blood based biomarker for allograft injury, donor-derived cell-free DNA (ddcfDNA), to examine the association of pre-HT AT1RAb to post-HT allograft injury. METHODS: AT1RAb testing was performed on pretransplant plasma from HT recipients in the Genomic Research Alliance for Transplantation (GRAfT) multicenter, prospective cohort study, using a quantitative ELISA (One Lambda, ThermoFisher). After HT, serial plasma samples were collected and used to quantitate %ddcfDNA by shotgun sequencing. AT1RAb concentration (units/ml) was used to categorize patients as AT1RAb<30 (n=32) or AT1RA>30 (n=17). A mixed linear model was used to examine post-HT %ddcfDNA trajectories across AT1RAb groups. Histopathology slides were read by a consensus of pathologists to define AMR using ISHLT criteria. RESULTS: Age, gender and clinical features were similar between AT1RAb<30 and AT1RA>30 groups. AT1RAb>30 had a greater proportion of White recipients compared to AT1RAb<30 (59% versus 38%; p = 0.003). While %ddcfDNA on posttransplant Day 1 were similar between AT1RAb<30 vs AT1RAb>30 (p=0.6), in the first year post-HT, ddcfDNA declined by 87% (95% CI 79%-92%) among patients with AT1RAb<30 vs 67% (CI=34%-84%) among patients with AT1RAb>30 (p = 0.04) (Figure). AMR in the first year post-HT was more common among AT1RAb>30 than AT1RAb<30 patients (18% vs 3%, p=0.07); CMR was comparable in each group (41% vs 24%, p=0.2). CONCLUSION: Preliminary analysis of this heart transplant cohort suggest that high pre-HT AT1RAb is associated with increased early post-HT allograft injury.

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine
  • Transplantation

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