title: Pre-transplant donor HLA-specific antibodies: characteristics causing detrimental effects on survival after lung transplantation.
abstract: BACKGROUND
  The impact of Luminex-detected HLA antibodies on outcomes after lung transplantation is unclear. Herein we have undertaken a retrospective study of pre-transplant sera from 425 lung transplants performed between 1991 and 2003.
  
  
  METHODS
  Pre-transplant sera, originally screened by complement-dependent cytotoxicity (CDC) assays, were retrospectively tested for the presence of HLA-specific antibodies using HLA-coated Luminex beads and C4d deposition on Luminex beads. The results were correlated with graft survival at 1 year.
  
  
  RESULTS
  Twenty-seven patients were retrospectively identified as having been transplanted against donor-specific HLA antibodies (DSA) and 36 patients against non-donor-specific HLA antibodies (NDSA). DSA-positive patients had 1-year survival of 51.9% compared with 77.8% for NDSA and 71.8% for antibody-negative patients (p = 0.029). One-year survival of patients with complement-fixing DSA was 12.5% compared with 62.5% for non-complement-fixing DSA, 75.8% for non-complement-fixing NDSA and 71.8% for antibody-negative patients (p < 0.0001). DSA-positive patients with mean fluorescence intensity (MFI) >5,000 had 1-year survival of 33.3% compared with 71.4% for MFI 2,000 to 5000 and 62.5% for MFI <2,000 (p = 0.0046). Multivariable analysis revealed DSA to be an independent predictor of poor patient survival within 1 year (p = 0.0010, hazard ratio [HR] = 3.569) as well as complement-fixing DSA (p < 0.0001, HR = 11.083) and DSA with MFI >5,000 (p = 0.0001, HR = 5.512).
  
  
  CONCLUSIONS
  Pre-formed DSA, particularly complement-fixing DSA, and high MFI are associated with poor survival within the first year after lung transplantation. Risk stratification according to complement fixation or MFI levels may allow for increased transplantation in sensitized patients.
authors: Tissue Typing Laboratory, Heart Science Centre, Harefield Hospital, Harefield, Middlesex, UK. Electronic address: j.smith@rbht.nhs.uk.
authors: John D
authors: JD
authors: Smith
authors: Department of Transplantation, Heart Science Centre, Harefield Hospital, Harefield, Middlesex, UK.
authors: Mohamed W
authors: MW
authors: Ibrahim
authors: Tissue Typing Laboratory, Heart Science Centre, Harefield Hospital, Harefield, Middlesex, UK.
authors: Helen
authors: H
authors: Newell
authors: Tissue Typing Laboratory, Heart Science Centre, Harefield Hospital, Harefield, Middlesex, UK.
authors: Anna J
authors: AJ
authors: Danskine
authors: Department of Transplantation, Heart Science Centre, Harefield Hospital, Harefield, Middlesex, UK.
authors: Simona
authors: S
authors: Soresi
authors: Department of Histopathology, Harefield Hospital, Heart Science Centre, Harefield Hospital, Harefield, Middlesex, UK.
authors: Margaret M
authors: MM
authors: Burke
authors: National Heart and Lung Institute, Imperial College, Heart Science Centre, Harefield Hospital, Harefield, Middlesex, UK.
authors: Marlene L
authors: ML
authors: Rose
authors: Department of Transplantation, Heart Science Centre, Harefield Hospital, Harefield, Middlesex, UK.
authors: Martin
authors: M
authors: Carby
mesh_terms: D000328:Adult; D064591:Allografts; D000906:Antibodies / Q000097:blood*; D005260:Female; D006084:Graft Rejection / Q000453:epidemiology* / Q000276:immunology / Q000401:mortality; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D015994:Incidence; D008171:Lung Diseases / Q000601:surgery; D016040:Lung Transplantation / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D057234:Preoperative Period; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D014019:Tissue Donors
chemical_list: D000906:Antibodies; D006680:HLA Antigens
keywords: HLA; Luminex-xmap; MFI; Pre-transplant; donor-specific antibodies; lung transplantation