Cardiac Allograft Outcomes: A Retrospective Study Correlating DSA, Endomyocardial Biopsy and Immunofluorescence
Renee Frank, Gerald Wertheim, Malek Kamoun, Priti Lal. Hospital of the University of Pennsylvania, Philadelphia; Children's Hospital of Philadelphia, Philadelphia
Background: Donor specific antibodies (DSAs) are clinically significant and have been associated with cardiac graft loss and a predisposition to coronary vasculopathy. Antibody-mediated rejection is a recognized clinicopathologic entity by the International Society for Heart and Lung Transplantation (ISHLT). Detection relies, in part, on the immunofluorescence (IF) pattern of C4d, serologic findings, and clinical picture.
Design: We performed a retrospective analysis of the relationship between DSA detection, IF, and clinical outcomes in cardiac transplant patients at our institution (2005-2011). DSA were evaluated against HLA class I and class II specificities pre and post transplant using flow cytometry and/or Luminex bead assays. Acute antibody-mediated rejection (AMR) was based on the ISHLT 2006 report, including diffuse interstitial capillary C4d and DSA presence. In addition to DSA and IF, we examined graft failure (mortality or graft replacement) as well as graft dysfunction as assessed by precipitous decrease in ejection fraction (EF) of at least 20%.
Results: 330 RVC biopsies and concurrent IF studies from 110 cardiac grafts in 109 patients, who had pre and post transplant DSA measurements, were analyzed. Of these, 50 grafts had DSA against either HLA class I, class II, or both. In patients with significant graft dysfunction (44), 78 of 109 biopsies correlated with a positive DSA. Of those 78 biopsies, only 18 exhibited diffuse C4d staining. In patients with graft failure who demonstrated DSA against class I only, class II only, or both, significant diffuse C4d staining was seen in 100% (2/2), 17% (1/6), and 71% (5/7) respectively. Patients with DSA to only class I or to both class I and class II had high graft failure rates of 40% (2/5) and 43% (9/20) with an average time to graft failure of 33 and 36 months, respectively. In contrast, patients who developed DSA to only class II exhibited a 24% (6/25) failure rate with an average time to graft failure of 95.8 months. Patients who did not develop DSA had a failure rate of 20% (12/60).
Conclusions: 1. Episodes of cellular rejection, but not AMR, may be a more frequent cause of graft dysfunction.
2. C4d tended to be a better indicator of graft failure in patients with DSA to both class I and class II or DSA to class I only than in patients with DSA to class II only.
3. Patients demonstrating DSA to class I only or DSA to both class I and II, have a decreased graft survival compared with patients demonstrating DSA to class II only.
Tuesday, March 20, 2012 2:15 PM
Platform Session: Section H2, Tuesday Afternoon