title: Analysis of preformed donor-specific anti-HLA antibodies characteristics for prediction of antibody-mediated rejection in kidney transplantation.
abstract: BACKGROUND
  The relevance of preformed donor specific antibodies (DSA) detected by Luminex assays, with a negative complement-dependent cytotoxicity (CDC) crossmatch, remains unsettled in kidney transplantation (KT). We aimed to analyze the impact of preformed DSA characteristics on kidney graft outcomes.
  
  
  METHODS
  In 462 patients that received a kidney graft in our unit, between 2007 and 2012, pre-transplant sera were analyzed by Luminex screening assay to determine the presence of anti-human leukocyte antigen (HLA) antibodies and single-antigen bead assay [positive if mean fluorescence intensity (MFI) ≥ 1000] to assign anti-HLA specificities.
  
  
  RESULTS
  Anti-HLA antibodies were present in 95 patients (20.6%), but only 40 (8.7%) had DSA. Antibody-mediated rejection (AMR) at 1-year was higher in patients with DSA (35.0%) than in those without them (0.9%) (P < 0.001). Only DSA with a MFI of >3000 were significantly associated with AMR occurrence. Receiver operator curves revealed that a MFI of >4900 in the highest DSA bead had a high sensitivity (85.7%) and that the sum of all DSA beads MFI > 11,000 had a high specificity (92.3%) for AMR prediction. Anti-thymocyte globulin versus basiliximab induction was more frequent in DSA+ AMR- (65.4%) versus DSA+ AMR+ (34.6%) patients (P = 0.072). Five-year censored graft survival was lower in DSA+ than in DSA- patients (respectively, 84.8% versus 94.9%, P = 0.006), although survival was only reduced in DSA+ AMR+ (68.8%) versus DSA+ AMR- (96.0%) patients (P = 0.038).
  
  
  CONCLUSIONS
  Preformed DSA is associated with kidney graft loss, in relation with AMR occurrence. DSA strength may be used to improve immunological risk stratification of sensitized patients and their clinical management.
authors: Nephrology and Kidney Transplantation Department, Hospital de Santo António, Centro Hospitalar do Porto, Largo Prof. Abel Salazar, 4099-001 Porto, Portugal; Unit for Multidisciplinary Investigation in Biomedicine (UMIB), ICBAS - Universidade do Porto, Rua de Jorge Viterbo Ferreira no. 228, 4050-313 Porto, Portugal. Electronic address: jjorgemalheiro@gmail.com.
authors: Jorge
authors: J
authors: Malheiro
authors: Centro do Sangue e Transplantação do Porto, Rua de Bolama no. 133, 4200-139 Porto, Portugal. Electronic address: Sandra.Tafulo@ipst.min-saude.pt.
authors: Sandra
authors: S
authors: Tafulo
authors: Nephrology and Kidney Transplantation Department, Hospital de Santo António, Centro Hospitalar do Porto, Largo Prof. Abel Salazar, 4099-001 Porto, Portugal. Electronic address: leonidiodias@sapo.pt.
authors: Leonídio
authors: L
authors: Dias
authors: Nephrology and Kidney Transplantation Department, Hospital de Santo António, Centro Hospitalar do Porto, Largo Prof. Abel Salazar, 4099-001 Porto, Portugal; Unit for Multidisciplinary Investigation in Biomedicine (UMIB), ICBAS - Universidade do Porto, Rua de Jorge Viterbo Ferreira no. 228, 4050-313 Porto, Portugal. Electronic address: lasalet@gmail.com.
authors: La Salete
authors: LS
authors: Martins
authors: Nephrology and Kidney Transplantation Department, Hospital de Santo António, Centro Hospitalar do Porto, Largo Prof. Abel Salazar, 4099-001 Porto, Portugal; Unit for Multidisciplinary Investigation in Biomedicine (UMIB), ICBAS - Universidade do Porto, Rua de Jorge Viterbo Ferreira no. 228, 4050-313 Porto, Portugal. Electronic address: isabelf27@gmail.com.
authors: Isabel
authors: I
authors: Fonseca
authors: Nephrology and Kidney Transplantation Department, Hospital de Santo António, Centro Hospitalar do Porto, Largo Prof. Abel Salazar, 4099-001 Porto, Portugal; Unit for Multidisciplinary Investigation in Biomedicine (UMIB), ICBAS - Universidade do Porto, Rua de Jorge Viterbo Ferreira no. 228, 4050-313 Porto, Portugal. Electronic address: idalina.m.b@gmail.com.
authors: Idalina
authors: I
authors: Beirão
authors: Nephrology and Kidney Transplantation Department, Hospital de Santo António, Centro Hospitalar do Porto, Largo Prof. Abel Salazar, 4099-001 Porto, Portugal; Unit for Multidisciplinary Investigation in Biomedicine (UMIB), ICBAS - Universidade do Porto, Rua de Jorge Viterbo Ferreira no. 228, 4050-313 Porto, Portugal. Electronic address: antonioach@hotmail.com.
authors: António
authors: A
authors: Castro-Henriques
authors: Nephrology and Kidney Transplantation Department, Hospital de Santo António, Centro Hospitalar do Porto, Largo Prof. Abel Salazar, 4099-001 Porto, Portugal. Electronic address: acabrita.nefrologia@chporto.min-saude.pt.
authors: António
authors: A
authors: Cabrita
mesh_terms: D000328:Adult; D018572:Disease-Free Survival; D005260:Female; D006084:Graft Rejection / Q000097:blood / Q000276:immunology* / Q000401:mortality*; D006680:HLA Antigens / Q000097:blood / Q000276:immunology*; D006801:Humans; D007518:Isoantibodies / Q000097:blood / Q000276:immunology*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D015996:Survival Rate
chemical_list: D006680:HLA Antigens; D007518:Isoantibodies
keywords: Antibody-mediated rejection; Donor-specific antibody; Graft survival; Kidney transplantation; Single-antigen bead assay