Survival in Sensitized Lung Transplant Recipients With Perioperative Desensitization

Abstract

Donor‐specific HLA antibodies (DSA) have an adverse effect on short‐term and long‐term lung transplant outcomes. We implemented a perioperative strategy to treat DSA‐positive recipients, leading to equivalent rejection and graft survival outcomes. Pretransplant DSA were identified to HLA‐A, B, C, DR and DQ antigens. DSA‐positive patients were transplanted if panel reactive antibody (PRA) ≥30% or medically urgent and desensitized with perioperative plasma exchange, intravenous immune globulin, antithymocyte globulin (ATG), and mycophenolic acid (MPA). PRA‐positive/DSA‐negative recipients received MPA. Unsensitized patients received routine cyclosporine, azathioprine and prednisone without ATG. From 2008–2011, 340 lung‐only first transplants were performed: 53 DSA‐positive, 93 PRA‐positive/DSA‐negative and 194 unsensitized. Thirty‐day survival was 96 %/99%/96% in the three groups, respectively. One‐year graft survival was 89%/88%/86% (p = 0.47). DSA‐positive and PRA‐positive/DSA‐negative patients were less likely to experience any ≥ grade 2 acute rejection (9% and 9% vs. 18% unsensitized p = 0.04). Maximum predicted forced expiratory volume (1 s) (81%/74%/76%, p = NS) and predicted forced vital capacity (81%/77%/78%, respectively, p = NS) were equivalent between groups. With the application of this perioperative treatment protocol, lung transplantation can be safely performed in DSA/PRA‐positive patients, with similar outcomes to unsensitized recipients.

IgM-Enriched Human Intravenous Immunoglobulin-Based Treatment of Patients With Early Donor Specific Anti-HLA Antibodies After Lung Transplantation

“…10,11,15-17,19 Hachem et al 17 reported the first case series on preemptive DSA treatment with IVIG and Rituximab in LTX.…”

“…1-9 The DSA treatment protocols have usually been borrowed from other solid organ transplantations. 10-19 However, overall experience with DSA treatment in LTX is scarce, and the available retrospective case series include limited numbers of patients. No randomized trials have been conducted.…”

Zbtb7a induction in alveolar macrophages is implicated in anti-HLA–mediated lung allograft rejection

“…Although the etiology of BOS is unclear and the mechanisms of lung allograft rejection are poorly defined, de novo antibody (Ab) to mismatched donor HLA (DSA), even when non-persistent, is a significant risk factor for CR (5–9). The immunodominant role of DSA in CR pathogenesis is supported by three distinct observations: 1) de novo DSA is associated with recurrent and high-grade cellular rejection and lymphocytic bronchiolitis (7, 10, 11) and an early de novo DSA is a significant risk factor for CR (12); 2) DSA development often precedes de novo Ab and T cell responses to lung-restricted SAgs (Collagen V [Col V] and K-alpha 1 Tubulin [Kα1T]) (8); and 3) DSA depletion via Ab-directed therapies lowers BOS hazard ratio and improves freedom from BOS (5, 13–15). …”

Autologous and Allogenous Antibodies in Lung and Islet Cell Transplantation

“…The immunodominant role of DSA in chronic rejection has been recognized by three distinct observations: (1) de novo DSA is associated with recurrent and high-grade cellular rejection and lymphocytic bronchiolitis (11, 15), (2) development of DSA often precedes de novo Col V- and Kα1T-specific Abs (26), and (3) depletion of the circulating Abs by Ab-directed therapy offers protection from BOS with a lower hazard ratio and enhanced pulmonary function (25, 27, 78–80). Preexisting Abs to Col V and Kα1T have been found in different terminal lung diseases pre-LTx, and such pretransplant autoantibodies were significantly correlated with poor outcomes, including development of DSA and BOS (33, 81).…”