Angiotensin II type I receptor agonistic autoantibodies are associated with poor allograft survival in liver retransplantation

Qingyong Xu, Vivian C McAlister, Steve Leckie, Andrew A House, Anton Skaro, Paul Marotta, Qingyong Xu, Vivian C McAlister, Steve Leckie, Andrew A House, Anton Skaro, Paul Marotta

Abstract

Angiotensin II type I receptor (AT1R) agonistic autoantibodies (AT1R-AA) are detrimental to kidney transplantation. Early studies suggested a similar negative effect in primary liver transplantation. Here, we studied AT1R-AA in a retrospective cohort of 94 patients who received a second liver transplant to determine their prevalence and effects. The concentrations of preformed AT1R-AA before transplantation were higher (P = .019) in the 48 patients who lost their liver grafts than in the 46 patients whose grafts survived. About half (48/94, 51.1%) of the patients were positive for AT1R-AA >17 U/mL before the second liver transplantation. In 22 (23.4%) patients, strong positive AT1R-AA (defined as >40 U/mL) were detected, of whom 16 (72.7%) patients lost their grafts. Based on Kaplan-Meier analysis, patients with strong positive AT1R-AA had significantly worse graft survival than those with AT1R-AA <40 U/mL (P = .035). In multivariate Cox models that included confounders such as sex and age, either AT1R-AA >40 U/mL (HR = 1.999 [1.085-3.682], P = .026) or increased concentrations of AT1R-AA (HR = 1.003 [1.001-1.006] per incremental U/mL, P = .019) were significantly associated with elevated risk for graft loss. In conclusion, our data indicate that there is a high prevalence of AT1R-AA in candidates for second liver transplantation and that their presence is associated with inferior long-term outcomes of the second graft.

Trial registration: ClinicalTrials.gov NCT03815864.

Keywords: autoantibody; clinical research/practice; immunobiology; liver allograft function/dysfunction; liver transplantation/hepatology; retransplantation; translational research/science.

© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.

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