title: A 3-Center Study Reveals New Insights Into the Impact of Non-HLA Antibodies on Lung Transplantation Outcome.
abstract: The presence of antibodies to angiotensin type 1 receptor (AT1R) and endothelin type A receptor (ETAR) is associated with allograft rejection in kidney and heart transplantation. The aim of our study was to determine the impact of AT1R and ETAR antibodies on graft outcome in lung transplantation.
  
  
  
  Pretransplant and posttransplant sera from 162 lung recipients transplanted at 3 centers between 2011 and 2013 were tested for antibodies to AT1R and ETAR 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.
  
  
  
  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 AT1R (P = 0.014) and ETAR (P = 0.005). Trends for lower freedom from acute cellular rejection were observed for recipients with pretransplant antibodies to AT1R (P = 0.19) and ETAR (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 AT1R (P = 0.054), ETAR (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 AT1R or ETAR, an increased negative impact on the freedom from the development of de novo DSA was observed (HR, 2.26 for HLA antibodies and ETAR; HR, 2.38 for HLA antibodies and ETAR).
  
  
  
  These results illustrate the increased negative impact when antibodies to both HLA and non-HLA antigens are present pretransplant.
authors.affiliation: 1 HLA Laboratory, Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA. 2 Biostatistics Core, Research Institute and General Clinical Research Center and Cardiothoracic Surgery, Cedars-Sinai Medical Center, Los Angeles, CA. 3 School of Pharmacy, University of Pittsburgh Medical Center, Pittsburgh, PA. 4 Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, PA. 5 Pulmonary, Critical Care Medicine, Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA. 6 University of Texas Health Science Center, San Antonio, TX. 7 Department of Immunology, University of Pittsburgh, Pittsburgh, PA.
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Reinsmoen
authors.forename: James
authors.initials: J
authors.lastname: Mirocha
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Ensor
authors.forename: Marilyn
authors.initials: M
authors.lastname: Marrari
authors.forename: George
authors.initials: G
authors.lastname: Chaux
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Levine
authors.forename: Xiaohai
authors.initials: X
authors.lastname: Zhang
authors.forename: Adriana
authors.initials: A
authors.lastname: Zeevi
mesh_terms: D018572:Disease-Free Survival; D004797:Enzyme-Linked Immunosorbent Assay; D006084:Graft Rejection / Q000097:blood / Q000276:immunology*; D006085:Graft Survival; D006680:HLA Antigens / Q000276:immunology; D006648:Histocompatibility; D006650:Histocompatibility Testing / Q000379:methods; D006801:Humans; D007518:Isoantibodies / Q000097:blood / Q000276:immunology*; D053208:Kaplan-Meier Estimate; D016040:Lung Transplantation / Q000009:adverse effects*; D044140:Receptor, Angiotensin, Type 1 / Q000276:immunology*; D044022:Receptor, Endothelin A / Q000276:immunology*; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
chemical_list: C544065:AGTR1 protein, human; D006680:HLA Antigens; D007518:Isoantibodies; D044140:Receptor, Angiotensin, Type 1; D044022:Receptor, Endothelin A