Occurrence of Fatal and Nonfatal Adverse Outcomes after Heart Transplantation in Patients with Pretransplant Noncytotoxic HLA Antibodies

HLA antibodies (HLA ab) in transplant candidates have been associated with poor outcome. However, clinical relevance of noncytotoxic antibodies after heart transplant (HT) is controversial. By using a Luminex-based HLA screening, we retested pretransplant sera from HT recipients testing negative for cytotoxic HLA ab and for prospective crossmatch. Out of the 173 consecutive patients assayed ( ; 16% females; 47% ischemic etiology), 32 (18%) showed pretransplant HLA ab, and 12 (7%) tested positive against both class I and class II HLA. Recipients with any HLA ab had poorer survival than those without ( versus %; ), accounting for a doubled independent mortality risk ( ). In addition, HLA-ab detection was associated with increased prevalence of early graft failure (35 versus 15%; ) and late cellular rejection (29 versus 11%; ). Of the subgroup of 37 patients suspected for antibody mediated rejection (AMR), the 9 with pretransplant HLA ab were more likely to display pathological AMR grade 2 ( ). By an inexpensive, luminex-based, HLA-screening assay, we were able to detect non-cytotoxic HLA ab predicting fatal and nonfatal adverse outcomes after heart transplant. Allocation strategies and desensitization protocols need to be developed and prospectively tested in these patients. 1. Introduction Short- and long-term mortality after heart transplantation (HT) has steadily decreased over time, reflecting the improvements in perioperative management and immunosuppressive therapy [1]. Nevertheless, even in the context of modern immunosuppressive strategies, the presence of preformed anti-human leukocyte antigens (HLA) antibodies (ab) in transplant candidates is still an important risk factor for allograft rejection and graft loss [2, 3]. In the last decade, the classical detection method based on complement dependent cytotoxicity (CDC) assays over a panel of leukocytes (panel reactive antibodies—PRA) has been replaced by more sensitive assays based on solid phase recognition of circulating ab [4]. These techniques allow detecting circulating anti-HLA ab in a higher number of patients than CDC assays, thus raising concerns regarding organ allocation and patient management during waiting list [5]. However, in what way the information from solid phase assays is translated into clinical practice to balance the risk of inappropriately delaying transplant on the one hand, or allocating organs likely to be affected by acute or chronic antibody mediated rejection on the other, is still a matter of investigation [4, 6]. Moreover, cost-effectiveness of the most sensitive