title: De Novo DQ Donor-Specific Antibodies Are Associated with Chronic Lung Allograft Dysfunction after Lung Transplantation.
abstract: Despite increasing evidence about the role of donor-specific human leukocyte antigen (HLA) antibodies in transplant outcomes, the incidence and impact of de novo donor-specific antibodies (dnDSA) after lung transplantation remains unclear.
  
  
  
  To describe the incidence, characteristics, and impact of dnDSA after lung transplantation.
  
  
  
  We investigated a single-center cohort of 340 lung transplant recipients undergoing transplant during 2008 to 2011. All patients underwent HLA-antibody testing quarterly pretransplant and at regular intervals over the first 24 months after transplant. The patients received modified immunosuppression depending on their pretransplant sensitization status. Risk factors for dnDSA development, as well as the associations of dnDSA with patient survival and chronic lung allograft dysfunction (CLAD), were determined using multivariable analysis.
  
  
  
  The cumulative incidence of dnDSA was 47% at a median of 86 days (range, 44-185 d) after lung transplantation. Seventy-six percent of recipients with dnDSA had DQ-DSA. Male sex and the use of ex vivo lung perfusion were associated with an increased risk of dnDSA, whereas increased HLA-DQB1 matching was protective. DQ-dnDSA preceded or coincided with the diagnosis of CLAD in all cases. Developing dnDSA (vs. no dnDSA) was associated with a twofold increased risk of CLAD (hazard ratio, 2.04; 95% confidence interval, 1.13-3.69). This association appeared to be driven by the development of DQ-dnDSA.
  
  
  
  dnDSA are common after lung transplantation, with the majority being DQ DSA. DQ-dnDSA are associated with an increased risk of CLAD. Strategies to prevent or treat DQ-dnDSA may improve outcomes for lung transplant recipients.
authors.affiliation: 1 Toronto Lung Transplant Program.
authors.forename: Jussi M
authors.initials: JM
authors.lastname: Tikkanen
authors.affiliation: 1 Toronto Lung Transplant Program.
authors.forename: Lianne G
authors.identifier: 0000-0002-2693-8676
authors.initials: LG
authors.lastname: Singer
authors.affiliation: 2 Division of Nephrology, Department of Medicine, and.
authors.forename: S Joseph
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: 2 Division of Nephrology, Department of Medicine, and.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Li
authors.affiliation: 1 Toronto Lung Transplant Program.
authors.forename: Matthew
authors.initials: M
authors.lastname: Binnie
authors.affiliation: 1 Toronto Lung Transplant Program.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Chaparro
authors.affiliation: 1 Toronto Lung Transplant Program.
authors.forename: Chung-Wai
authors.initials: CW
authors.lastname: Chow
authors.affiliation: 1 Toronto Lung Transplant Program.
authors.forename: Tereza
authors.initials: T
authors.lastname: Martinu
authors.affiliation: 1 Toronto Lung Transplant Program.
authors.forename: Sassan
authors.initials: S
authors.lastname: Azad
authors.affiliation: 1 Toronto Lung Transplant Program.
authors.forename: Shaf
authors.initials: S
authors.lastname: Keshavjee
authors.affiliation: 2 Division of Nephrology, Department of Medicine, and.|3 HLA Laboratory, Laboratory Medicine Program, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Tinckam
mesh_terms: D064591:Allografts / Q000276:immunology* / Q000706:statistics & numerical data; D001989:Bronchiolitis Obliterans / Q000453:epidemiology / Q000209:etiology / Q000276:immunology*; D005260:Female; D006084:Graft Rejection / Q000150:complications / Q000453:epidemiology / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D053208:Kaplan-Meier Estimate; D008168:Lung / Q000276:immunology*; D016040:Lung Transplantation / Q000009:adverse effects* / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D009864:Ontario / Q000453:epidemiology; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D017678:Sex Distribution; D014019:Tissue Donors
chemical_list: D006680:HLA Antigens; D007166:Immunosuppressive Agents
keywords: bronchiolitis obliterans syndrome; chronic lung allograft dysfunction; donor-specific antibodies; lung transplantation