title: Donor-specific antibodies are associated with antibody-mediated rejection, acute cellular rejection, bronchiolitis obliterans syndrome, and cystic fibrosis after lung transplantation.
abstract: BACKGROUND
  Lung transplantation is limited by chronic lung allograft dysfunction. Acute cellular rejection (ACR) is a risk factor for allograft dysfunction; however, the role of antibody-mediated rejection (AMR) is not well characterized.
  
  
  METHODS
  This was a retrospective review from 2007 to 2011 of lung transplant recipients with human leukocyte antigen (HLA) antibody testing using Luminex (Luminex Corp, Austin, TX) single-antigen beads. Statistics included Fisher's exact test for significance.
  
  
  RESULTS
  Donor-specific antibodies (DSA) developed in 13 of 44 patients. Of the 13 with DSA, 12 had cystic fibrosis compared with 18 of 31 in the non-DSA group (p = 0.035). Of those with DSAs, 23.1% occurred within the first year, and 69.2% occurred between 1 and 3 years. Twelve of 13 DSA patients had anti-HLA DQ specificity compared with 2 of 31 non-DSA patients (p = 0.0007). AMR developed in 10 of the 13 DSA patients compared with 1 of 31 non-DSA patients (p = 0.0001). The DSA group experienced 2.6 episodes/patient of cellular rejection vs 1.7 episodes/patient in the non-DSA group (p = 0.059). Bronchiolitis obliterans syndrome developed in 11 of 13 in the DSA group vs 10 of 31 in the non-DSA group (p = 0.0024). In the DSA group, 11.5% HLAs matched compared with 20.4% in the non-DSA group (p = 0.093). AMR developed in 11 of 22 patients in the non-DSA HLA group compared with 0 of 22 in the group without non-DSA HLA antibodies (p = 0.002). Survival at 1 and 3 years was 92% and 36% in the DSA group, respectively, and 97% and 65% in the non-DSA group.
  
  
  CONCLUSIONS
  DSAs and non-DSAs occur frequently after lung transplantation. DSAs are prevalent in the cystic fibrosis population and are associated with AMR, bronchiolitis obliterans syndrome, and possibly, ACR.
authors.affiliation: University of North Carolina, Division of Pulmonary and Critical Care Medicine, 130 Mason Farm Rd, Campus Box 7020, Chapel Hill, NC 27599, USA. leonardlobo@gmail.com
authors.forename: Leonard J
authors.initials: LJ
authors.lastname: Lobo
authors.forename: Robert M
authors.initials: RM
authors.lastname: Aris
authors.forename: John
authors.initials: J
authors.lastname: Schmitz
authors.forename: Isabel P
authors.initials: IP
authors.lastname: Neuringer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000906:Antibodies / Q000276:immunology*; D001989:Bronchiolitis Obliterans / Q000276:immunology*; D003550:Cystic Fibrosis / Q000276:immunology*; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D016040:Lung Transplantation / Q000009:adverse effects* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D014019:Tissue Donors; D055815:Young Adult
chemical_list: D000906:Antibodies