The Role of Donor-Specific Antibodies in Acute Cardiac Allograft Dysfunction in the Absence of Cellular Rejection

Abstract

Background Acute allograft dysfunction (AAD) is an important cause of morbidity among heart transplant recipients. The role of donor specific antibodies (DSA) in AAD, with the increasing use of Single Antigen Bead (SAB) assays that have improved the ability to detect DSA, remains unclear. Methods We retrospectively reviewed 329 heart transplant recipients followed at our institution. AAD was defined as an acute decline in left ventricular ejection fraction to <50% and a decrement of ≥10% compared to baseline in the absence of cellular rejection. AAD patients were compared with matched 30 heart transplant controls. Results There were 10 (3%) patients with AAD, 4 (40%) had DSA detectable by SAB assay compared to 16 (53%) controls (p=0.43). Peak DSA mean fluorescent intensity levels (MFI) were significantly higher at baseline (class I and class II) in AAD compared to controls. DSA MFI values increased at the time of AAD and returned to baseline values in follow-up for these AAD patients (p<0.05), but remained unchanged over time for controls. Six (60%) patients and 1 (3%) control had antibody-mediated rejection (AMR) by endomyocardial biopsy (p<0.01). There were 4 (40%) AAD patients with no DSA or AMR. Conclusions AAD after heart transplant is a heterogeneous process characterized by: 1) AMR and DSA, 2) AMR but no DSA, and 3) No AMR or DSA. The presence of DSA is not associated with AAD but quantity assessed by MFI levels may play a role.

Effect of persistent versus transient donor-specific HLA antibodies on graft outcomes in pediatric cardiac transplantation

“…3,23,24 More recent studies have addressed the use of MFI levels for HLA antibodies and found some utility in using these measurements in acute allograft vasculopathy. 25 There is increasing evidence, however, that Class II DSA are more strongly associated with long-term chronic rejection, particularly in the form of CAV. 6,26 Interestingly, Smith et al 5 showed no association between HLA antibodies (DSA or non-DSA) and the development of CAV.…”

Outcomes of Induction Therapy with Rabbit Anti-Thymocyte Globulin in Heart Transplant Recipients: A Single Center Retrospective Cohort Study

“…Awareness of the prognostic importance of DSAs is influencing initial immunosuppressive protocols according to patients’ pre-transplantation DSA status. Recipients with pre-transplantation DSA are far more likely to experience antibody-mediated or cellular rejection and graft failure despite desensitization measures, which is hard to apply to heart transplantation as the pool of organs is smaller, heart grafts are less well-matched than other organs, transplantation is more urgent, and graft storage times are shorter, and it is often not possible to await the results of cross-match testing [ 16 , 20 – 23 ].…”

Nonhuman leukocyte antigen antibodies that have impact in the heart transplant patient

“…Acute cardiac allograft dysfunction without the presence of donor-specific anti-HLA antibodies can occur in up to 40% of cases. Most of these heart transplant recipients are responsive to augmented immunosuppression suggestive of immune-mediated non-HLA-mediated graft dysfunction [6].…”