The Presence of HLA-Directed Antibodies after Heart Transplantation Is Associated with Poor Allograft Outcome

Abstract

The clinical significance of HLA-directed antibodies newly detected after transplantation (HT) is controversial. Seventy-one HT recipients consented to enroll. Mean follow-up time was 28 months (range 6-48). Panel reactive antibody (PRA) analysis was performed on posttransplant sera (2 weeks, 1, 2, 3, 6, and 12 months and annually thereafter) using Flow-PRA. A mean of 6.9+/-1.2 serum samples per patient were obtained. Severity of cellular rejection was measured using the ISHLT grading system. Coronary angiography and intravascular ultrasound (IVUS) studies were performed annually to evaluate severity of allograft vasculopathy. Twenty-five recipients had newly detected HLA-directed antibodies during the first year postHT. HLA class I antibodies were detected in 18 patients (25.4%), and class II in 11 patients (15.5%). The majority of donor recipient pairs were HLA mismatched (4.6+/-1.2 of the six major HLA antigens). Only mismatches at HLA-A locus had significant association with de novo posttransplant antibody formation. Length of ischemia time was correlated with early and sustained presence of de novo HLA-directed antibodies postheart transplant. Importantly, an association between de novo HLA-directed antibodies and cellular rejection was notes (P=0.0002). De novo HLA class II directed antibodies are also associated with IVUS documented vasculopathy (P<0.002). Finally, death due to allograft failure is associated with the presence of de novo formed HLA class II directed antibodies (P=0.008). Identifying the formation of de novo HLA-directed antibodies following heart transplantation may predict allograft outcome. This, in turn, may serve as a tool for individualization of immunosuppression protocols in heart transplant recipients.