Abstract
There is increasing evidence that de novo donor-specific HLA antibodies (DSA) are associated with poor outcome following cardiac transplantation. Management of these remains problematic and there is little data on lag time from DSA development to an adverse event. We aimed to determine average time from first detection of DSA to rejection, cardiac allograft vasculopathy(CAV) or graft loss in a pediatric cohort.
Luminex screens and single antigen tests were performed on stored samples taken at 3, 6, 12 months and then annually in patients transplanted age <18 years in 1996-2010. Time from DSA detection to adverse outcome was analysed.
108 patients, mean age at transplant 7.4 (0.1-15.9) years were studied, mean follow-up 8.2 (1.9-15.7) years. All had a CDC-negative crossmatch and retrospective serum analysis confirmed they had no DSA prior to transplant. 43/108 (40%) patients had DSA with median time from transplant to DSA development of 2 (0.25-11) years. Freedom from DSA was 91% at 3 months, 86% at 6 months, 84% at 1 year, 69% at 5 years, 58% at 10 years and 48% at 15 years post-transplant. 9 patients with DSA (21%) developed CAV, and in 6 (67%), DSA were detected prior to CAV diagnosis with median lag time of 2.2 (1-4.9) years. 14 patients (33%) had a rejection episode, 9 (64%) had DSA prior to rejection with median lag time time of 2.8 (0.2-7.2) years. 10 patients (23%) died or were re-transplanted, with median time from development of DSA to graft loss of 1.7 (0.1-4.8) years. 28/33 (85%) patients with an adverse outcome had Class II DSA with anti-DQ the most prevalent.
In patients with DSA in whom an adverse event occurred (CAV, Rejection or Graft loss) DSA were detected in 25/33 (76%) prior to the adverse outcome. The majority of patients with an adverse outcome in this study had Class II DSA detected prior to that event. These findings suggest that once DSAs have developed increased surveillance for adverse events should be implemented.