Human Leukocyte Antigen-Based Risk Stratification in Heart Transplant Recipients—Implications for Targeted Surveillance

Abstract

Background: Human leukocyte antigen (HLA) matching isn't routinely performed in heart transplantation. Novel allograft perfusion methods may make HLA matching feasible. The purpose of this study is to reexamine whether HLA mismatch may be used in risk stratification to improve outcomes in heart transplantation. Methods and Results: We analyzed 34 681 recipients undergoing heart transplantation between 1987 and 2013. We used HLAMatchmaker to quantify HLA eplet mismatches and Cox regression for analysis of time to graft loss. Recipients with 4 mismatched HLA-DR/DQ alleles and >40 eplets reached an adjusted hazard ratio (HR) for graft loss of 1.17 (95% CI 1.07–1.28) and 1.11 (95% CI 1.03–1.21), respectively. We found significant interaction between recipient age and numbers of HLA-DR/DQ allele and eplet mismatches resulting in an adjusted HR of 1.78 (95% 1.13–2.80) and 1.82 (95% CI, 1.23–2.70), respectively. HR for both interaction terms was 0.99 (95% CI, 0.98–1.00). Risk of graft loss was more pronounced after 1 year, where recipient <40 years with 4 mismatched HLA-DR/DQ alleles and >40 eplets had an adjusted HR of 1.51 (95% CI 1.12–2.03) and 1.32 (95% CI 1.02–1.70), respectively. Pre-sensitized recipients with panel reactive antibodies >10% had an adjusted HR=1.27 (95% CI 1.16–1.40) for graft loss within 1 year but not thereafter. HLA eplet mismatch was independent of panel reactive antibodies on reduction of graft loss within and after 1 year, P (interaction)=0.888 and 0.389. Conclusions: HLA mismatch may be used in risk stratification for intensified post-transplant surveillance and therapy.