A 3-Center Study Reveals New Insights Into the Impact of Non-HLA Antibodies on Lung Transplantation Outcome. Issue 6 (June 2017)

• Record Type: Journal Article
• Authors: Reinsmoen, Nancy L.; Mirocha, James; Ensor, Christopher R.; Marrari, Marilyn; Chaux, George; Levine, Deborah J.; Zhang, Xiaohai; Zeevi, Adriana
• Is Part Of: Transplantation. Volume 101:Issue 6(2017)
• Publication Date: 2017-06
• Subjects: Transplantation of organs, tissues, etc -- Periodicals; Transplantation immunology -- Periodicals; 617.95
• DOI: 10.1097/TP.0000000000001389
• Languages: English
• ISSNs: 0041-1337

Abstract

Abstract : Background: The presence of antibodies to angiotensin type 1 receptor (AT1 R) and endothelin type A receptor (ETA R) is associated with allograft rejection in kidney and heart transplantation. The aim of our study was to determine the impact of AT1 R and ETA R antibodies on graft outcome in lung transplantation. Methods: Pretransplant and posttransplant sera from 162 lung recipients transplanted at 3 centers between 2011 and 2013 were tested for antibodies to AT1 R and ETA R by the enzyme-linked immunosorbent assay (ELISA) assay. Clinical parameters analyzed were: HLA antibodies at transplant, de novo donor-specific antibodies (DSA), antibody-mediated rejection (AMR), acute cellular rejection, and graft status. Results: Late AMR (median posttransplant day 323) was diagnosed in 5 of 36 recipients with de novo DSA. Freedom from AMR significantly decreased for those recipients with strong/intermediate binding antibodies to AT1 R ( P = 0.014) and ETA R ( P = 0.005). Trends for lower freedom from acute cellular rejection were observed for recipients with pretransplant antibodies to AT1 R ( P = 0.19) and ETA R ( P = 0.32), but did not reach statistical significance. Lower freedom from the development of de novo DSA was observed for recipients with antibodies detected pretransplant to AT1 R ( P = 0.054), ETA R ( P = 0.012), and HLA-specific antibodies ( P = 0.063). When the pretransplant antibody status of HLA-specific antibody (hazard ratio [HR], 1.69) was considered together with either strong binding to AT1 R or ETA R, an increased negative impact on the freedom from the development of de novo DSA was observed (HR, 2.26 for HLA antibodies and ETA R; HR, 2.38 for HLA antibodies and ETA R). Conclusions: These results illustrate the increased negative impact when antibodies to both HLA and non-HLA antigens are present pretransplant. Abstract : In 162 lung transplant recipients from 3 centers, freedom from antibody-mediated rejection is decreased in recipients with intermediate to strong nonHLA antibodies (AT1R and ETAR) while the occurrence of posttransplant de novo DSAs is increased in patients with pretransplant HLA antibodies together with nonHLA antbodies.