De Novo Anti-HLA Antibodies After Heart Transplantation Are Associated With Adverse Events in the Long-term Follow-up of Cardiac Transplant Recipients

Abstract

Background and objectives: Long-term morbidity and mortality after heart transplantation (HTx) remain very high. Several reports have suggested that anti-HLA antibodies (anti-HLA-AB) detected after HTx might be associated with poor survival, but the implication of isolated anti-HLA-AB is still under debate. The aim of the study was to analyze the incidence of de novo anti-HLA-AB and whether they are associated with adverse events after HTx.

Methods: This retrospective study analyzed the presence of anti-HLA-AB assessed by fluorimetry (Luminex) and quantified by a single-antigen bead assay in 119 HTx patients. Mortality, graft dysfunction, antibody-mediated rejection (AMR), and cardiac allograft vasculopathy (CAV) were recorded. Cardiovascular mortality of patients with and without anti-HLA-AB was compared according Kaplan-Meier curves. Cox regression analyses were performed to identify predictors for global mortality and for a combined endpoint (cardiovascular mortality, AMR, and CAV). Mean age of recipients and donors was 49 ± 15 and 38 ± 14 years, 70% were men, 29% were urgent transplants, and mean ischemic time was 195 ± 56 minutes.

Results: Anti-HLA-AB were detected in 23 patients (19%). These patients had higher rates of AMR (39% vs 1%; P < .05) and cardiovascular mortality (17% vs 2%; P < .05). By multivariate analysis, anti-HLA-AB were the only predictor of the combined endpoint (hazard ratio 3.1; confidence interval 1.3 to 7.5; P = .01). Kaplan-Meier curves showed the worse cardiovascular survival of patients with anti-HLA-AB (72% vs 97%; P = .003).

Conclusions: Presence of anti-HLA-AB identifies a group of HTx patients with worse prognosis. Better understanding of the immunologic relevance of anti-HLA-AB is expected to improve long-term survival after HTx.