title: De novo donor HLA-specific antibodies predict development of bronchiolitis obliterans syndrome after lung transplantation.
abstract: BACKGROUND
  Bronchiolitis obliterans syndrome (BOS) is the major cause of late graft failure after lung transplantation. The objective was to determine whether de novo donor human leukocyte antigen (HLA)-specific antibodies (DSA) are associated with the development of BOS or patient survival. Data were analyzed from 188 lung transplant recipients with a follow-up period up to 8 years.
  
  
  METHODS
  HLA antibody monitoring was performed at 3-month intervals post-transplant at routine outpatient clinic attendances and during the investigation of any acute deterioration. HLA antibody data were available for 148 patients; 66 (45%) had produced HLA antibodies after transplant, of which 38 (26%) were DSA and 28 (19%) non-donor-specific HLA antibodies.
  
  
  RESULTS
  De novo DSA was associated with development of BOS Stage 1 (BOS1; hazard ratio [HR] = 2.302, p = 0.0015), BOS2 (HR = 3.627, p < 0.0001) and BOS3 (HR = 5.736, p < 0.0001). De novo persistent DSA correlated strongly with shorter time to onset of BOS3 (HR = 6.506, p = 0.0001). There was a significant reduction in patient survival associated with de novo DSA (HR = 1.886, p = 0.047). In multivariable analyses, de novo DSA was an independent predictor for development of all stages of BOS as well as an independent predictor of poor patient survival.
  
  
  CONCLUSIONS
  De novo DSA is a major risk factor for progression to BOS and shorter patient survival. Treatments to remove antibodies or limit antibody-mediated damage could be considered when DSA are first detected. However, a randomized, controlled trial of treatment options would enable a clearer understanding of the benefits, if any, of antibody-removal therapies.
authors.affiliation: Department of Transplantation, Harefield Hospital, Middlesex, UK.
authors.forename: Shahideh
authors.initials: S
authors.lastname: Safavi
authors.affiliation: Mathematics Department, University of Sussex, Brighton, Middlesex, UK.
authors.forename: Derek R
authors.initials: DR
authors.lastname: Robinson
authors.affiliation: Department of Transplantation, Harefield Hospital, Middlesex, UK.
authors.forename: Simona
authors.initials: S
authors.lastname: Soresi
authors.affiliation: Department of Transplantation, Harefield Hospital, Middlesex, UK.
authors.forename: Martin
authors.initials: M
authors.lastname: Carby
authors.affiliation: Tissue Typing Laboratory, Heart Science Centre, Harefield Hospital, Harefield, Middlesex, UK. Electronic address: j.smith@rbht.nhs.uk.
authors.forename: John D
authors.initials: JD
authors.lastname: Smith
mesh_terms: D000328:Adult; D000888:Antibodies, Anti-Idiotypic / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001989:Bronchiolitis Obliterans / Q000453:epidemiology* / Q000276:immunology* / Q000401:mortality; D005260:Female; D005500:Follow-Up Studies; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D008137:Longitudinal Studies; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011184:Postoperative Period; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D014019:Tissue Donors
chemical_list: D000888:Antibodies, Anti-Idiotypic; D015415:Biomarkers; D006680:HLA Antigens
keywords: Luminex-xmap; MFI; bronchiolitis obliterans syndrome; donor-specific antibodies; lung transplantation