Panel-Reactive Antibody Associated with Acute Rejection Episodes After Heart Transplantation: An Analysis of the UNOS Database

Abstract

<h3>Purpose</h3> The presence of circulating alloantibodies can prolong transplant waiting times and may be associated with worse post-transplant outcomes. Recently, patients undergoing heart transplantation have been found to possess higher panel reactive antibody (PRA) levels, but the impact of this finding is uncertain. We aimed to determine the association between an elevated PRA and subsequent episodes of acute rejection. <h3>Methods</h3> Using the United Network for Organ Sharing (UNOS) Standard Transplant Analysis and Research Database, we retrospectively reviewed HTs performed from January 2004 to September 2020. Multi-organ transplants and re-transplants were excluded from analysis. Site-reported "Most recent PRA Class I" and "Most Recent PRA Class II" were used to assess PRA level, and the "Acute Rejection Episodes" variable was used to identify acute rejection, regardless of use of anti-rejection therapies. Detection methodology between centers could vary. Patients were stratified into three groups: 1) No-PRA (PRA% = 0), 2) Some-PRA (PRA% >0 and <50), and 3) High-PRA (PRA% >50). Rates of acute rejection were compared by log-rank test, with multivariate analysis adjusting for clinically relevant factors. <h3>Results</h3> A total of 41,537 patients were included in this study. Approximately 19% of patients experienced at least one acute rejection event. When stratifying based on Most Recent PRA Class I, the Some-PRA and High-PRA groups had significantly higher rates of acute rejection episodes, OR 1.22 (95% CI 1.12-1.33, p <0.001) and OR 1.79 (95% CI 1.55-2.06, p <0.001), respectively. Similar findings were obtained when using Most Recent PRA Class II, OR 1.31, (95% CI 1.19-1.45, p <0.001) and OR 1.71 (95% CI 1.47-1.99, p <0.001), respectively. When adjusting for sex and pre-operative blood transfusions, the results remained generally consistent - Class I: OR 3.9 (95% CI 1.04-17, p <0.05) and OR 3.2 (95% CI 0.13-37, p = 0.38), respectively; Class II: OR 3.79 (95% CI 0.94-17, p = 0.065) and OR 18.58 (95% CI 1.42-467, p <0.05), respectively. <h3>Conclusion</h3> Elevated PRA levels are associated with acute rejection episodes after HT, irrespective of patient sex and pre-operative blood transfusions. Further research should be conducted to verify our findings prospectively and account for possible confounders.