title: Pre-transplant presence of antibodies to MICA and HLA class I or II are associated with an earlier onset of bronchiolitis obliterans syndrome in lung transplant recipients.
abstract: Previous reports using cell-based methods (CDC-AHG) suggest that the presence of pre-transplant HLA Class I and II antibodies are associated with worse survival following lung transplantation. Similarly, antibodies to major histocompatibility complex Class I chain-related gene A (MICA) have been associated with increased graft failure following kidney transplantation. Using highly sensitive solid phase assays, we sought to determine whether the pre-transplant presence of antibodies to MICA or HLA Class I or II predicted short or long-term lung allograft function. Pre-transplant sera screened for antibodies to MICA by Labscreen Single Antigen format and HLA by Luminex (n = 192) revealed antibody presence in 31 (16.1%) and 70 (36.4%) patients, respectively. HLA antibody presence correlated with increased bronchiolitis Obliterans syndrome (BOS)-1 development at 3 years [32.9% (23/70) vs. 18.9% (23/122), p = 0.03] while MICA antibodies correlated with BOS-2 development [32.3% (10/31) vs. 14.9% (24/161), p = 0.02]. The presence of HLA or MICA antibodies correlated with BOS-1 development [32.5% (26/81) vs.18.0% (20/111), p = 0.02] and BOS-2 [24.7% (20/81) vs. 12.6% (14/111), p = 0.02] at 3 years. We found no correlation between antibody presence and episodes of acute cellular rejection or overall survival. We conclude that the presence of pre-transplant HLA or MICA antibodies is associated with earlier BOS onset following lung transplantation.
authors.affiliation: University of Colorado Denver, Aurora, Colorado, USA. dennis.lyu@ucdenver.edu
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Lyu
authors.forename: Todd J
authors.initials: TJ
authors.lastname: Grazia
authors.forename: Alex B
authors.initials: AB
authors.lastname: Benson
authors.forename: Linda R
authors.initials: LR
authors.lastname: Cagle
authors.forename: Brian M
authors.initials: BM
authors.lastname: Freed
authors.forename: Martin R
authors.initials: MR
authors.lastname: Zamora
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D001989:Bronchiolitis Obliterans / Q000453:epidemiology / Q000276:immunology*; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D016040:Lung Transplantation / Q000009:adverse effects / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000453:epidemiology / Q000276:immunology; D011237:Predictive Value of Tests; D011300:Preoperative Care; D012307:Risk Factors; D016036:Seroepidemiologic Studies; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D001323:Autoantibodies; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; C099187:MHC class I-related chain A