title: HLA Matching at the Eplet Level Protects Against Chronic Lung Allograft Dysfunction.
abstract: Donor selection in lung transplantation (LTx) is historically based upon clinical urgency, ABO compatibility, and donor size. HLA matching is not routinely considered; however, the presence or later development of anti-HLA antibodies is associated with poorer outcomes, particularly chronic lung allograft dysfunction (CLAD). Using eplet mismatches, we aimed to determine whether donor/recipient HLA incompatibility was a significant predictor of CLAD. One hundred seventy-five LTx undertaken at the Alfred Hospital between 2008 and 2012 met criteria. Post-LTx monitoring was continued for at least 12 months, or until patient death. HLA typing was performed by sequence-based typing and Luminex sequence-specific oligonucleotide. Using HLAMatchmaker, eplet mismatches between each donor/recipient pairing were analyzed and correlated against incidences of CLAD. HLA-DRB1/3/4/5+DQA/B eplet mismatch was a significant predictor of CLAD (hazard ratio [HR] 3.77, 95% confidence interval [CI]: 1.71-8.29 p < 0.001). When bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS) were analyzed independently, HLA-DRB1/3/4/5 + DQA/B eplet mismatch was shown to significantly predict RAS (HR 8.3, 95% CI: 2.46-27.97 p < 0.001) but not BOS (HR 1.92, 95% CI: 0.64-5.72, p = 0.237). HLA-A/B eplet mismatch was shown not to be a significant predictor when analyzed independently but did provide additional stratification of results. This study illustrates the importance of epitope immunogenicity in defining donor-recipient immune compatibility in LTx.
authors.affiliation: Victorian Transplantation and Immunogenetics Service, Australian Red Cross Blood Service, Melbourne, Australia.
authors.forename: D C
authors.initials: DC
authors.lastname: Walton
authors.affiliation: Victorian Transplantation and Immunogenetics Service, Australian Red Cross Blood Service, Melbourne, Australia.
authors.forename: S J
authors.initials: SJ
authors.lastname: Hiho
authors.affiliation: Victorian Transplantation and Immunogenetics Service, Australian Red Cross Blood Service, Melbourne, Australia.
authors.forename: L S
authors.initials: LS
authors.lastname: Cantwell
authors.affiliation: Victorian Transplantation and Immunogenetics Service, Australian Red Cross Blood Service, Melbourne, Australia.
authors.forename: M B
authors.initials: MB
authors.lastname: Diviney
authors.affiliation: Research and Development, Australian Red Cross Blood Service, Sydney, Australia.|Mathematical and Physical Sciences, University of Technology Sydney, Sydney, Australia.
authors.forename: S T
authors.initials: ST
authors.lastname: Wright
authors.affiliation: Lung Transplant Service, Alfred Hospital, Melbourne, Australia.
authors.forename: G I
authors.initials: GI
authors.lastname: Snell
authors.affiliation: Lung Transplant Service, Alfred Hospital, Melbourne, Australia.
authors.forename: M A
authors.initials: MA
authors.lastname: Paraskeva
authors.affiliation: Lung Transplant Service, Alfred Hospital, Melbourne, Australia.
authors.forename: G P
authors.initials: GP
authors.lastname: Westall
mesh_terms: D000328:Adult; D000465:Algorithms; D064591:Allografts; D001989:Bronchiolitis Obliterans / Q000209:etiology / Q000517:prevention & control*; D002908:Chronic Disease; D015331:Cohort Studies; D000939:Epitopes / Q000276:immunology; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000209:etiology / Q000517:prevention & control*; D006085:Graft Survival; D006683:HLA-DQ Antigens / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology*; D006648:Histocompatibility; D006801:Humans; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D011379:Prognosis; D014019:Tissue Donors
chemical_list: D000939:Epitopes; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens
keywords: basic (laboratory) research/science; bronchiolitis obliterans (BOS); clinical research/practice; histocompatibility; lung (allograft) function/dysfunction; lung transplantation/pulmonology; major histocompatibility complex (MHC); organ transplantation in general