Clinical Consequences of Preoperative anti-HLA Antibodies and Panel Reactive Antibodies in Heart Transplantation

Abstract

Purpose Novel solid phase assays provide new insights into pathophysiology of antibody mediated allograft injury in heart transplant (HTx) recipients. We aimed to evaluate clinical consequences of pre-transplant anti-HLA antibodies detected both by Luminex ® and classical cytotoxic test (panel reactive antibodies, PRA). Methods and Materials The study group included 185 de-novo HTx recipients [148 males (80%), age 50±12 years]. They received induction with antithymocyte globulin followed by standard immunosuppression (tacrolimus/cyclosporine + mycophenolate mophetil + prednisone). We analysed pretransplant sera using a solid phase assay Luminex ® and reviewed results of PRA. Occurrence of antibody mediated rejection (AMR), acute cellular rejection (ACR) and all-cause mortality were analysed during a median follow-up of 37 months (20-59). Results The peak PRA ≥10% and PRA ≥ 15% were present in 20% and 18% of individuals, respectively. Anti-HLA antibodies class I, class II, MICA antibodies and donor specific antibodies (DSA) were detected in 37 pts (20%), 15 pts (8%), 25 pts (13%) and 23 pts (12%), respectively. Clinically significant AMR and ACR were diagnosed in 11 pts (5.9%) and 59 pts (32%), respectively. The best predictors of AMR were anti-HLA antibodies class I and peak PRA ≥ 15%. Positivity of one of these two variables predicted AMR with a sensitivity of 73% and specificity of 68%, p=0.009. Neither PRA nor anti-HLA antibodies were related to ACR or all-cause death. Survival was 93% and 79% at 12 months and 5 years, respectively. Conclusions Combination of Luminex ® assay and panel reactive antibodies provides reasonable prediction of antibody mediated rejection. Supported by the research grant IGA MZ CR – NT 11262-6.