Anti-AT1R autoantibodies in pancreas transplantation

Autoantibodies targeting the angiotensin II receptor type 1 (AT1R) have been identified as drivers of allograft vascular inflammation in kidney transplantation. We investigated the role of AT1R autoantibodies (AT1R-AA) in pancreas transplantation with a focus on rejection and thrombosis. We included all pancreas transplant recipients followed in our center with available pretransplant sera (day 0). AT1R-AA levels were assessed, and a multivariable cause-specific Cox model was used to examine their association with pancreas rejection and survival. Additionally, pancreatic tissues were analyzed for AT1R expression at the molecular and protein levels. Among 305 patients, 34 experienced pancreatic rejection and 50 allografts were lost at 1 year. In multivariable analysis, AT1R-AA titer at transplantation was significantly associated with pancreas survival (adjusted hazard ratio = 1.04, 95% confidence interval [1.00; 1.08], P = .0427) and pancreas rejection (adjusted hazard ratio = 1.07, 95% confidence interval [1.03; 1.12], P = .0015). AT1R-AA levels were significantly higher in patients with early thrombosis compared with others (10.1 U/mL vs 6.3 U/mL, P < .0001). Analysis of tissues from deceased donors and follow-up biopsies revealed wide variation in pancreatic AT1R expression. In conclusion, AT1R-AA were significantly associated with a higher risk of pancreatic rejection and allograft failure from complete thrombosis. Variations in pancreatic AT1R expression may contribute to different outcomes among patients with pretransplant AT1R-AA.