期刊
AMERICAN JOURNAL OF TRANSPLANTATION
卷 16, 期 9, 页码 2695-2703出版社
WILEY-BLACKWELL
DOI: 10.1111/ajt.13798
关键词
clinical research; practice; basic (laboratory) research; science; lung transplantation; pulmonology; organ transplantation in general; histocompatibility; bronchiolitis obliterans (BOS); lung (allograft) function; dysfunction; major histocompatibility complex (MHC)
资金
- Margaret Pratt Foundation
- Alfred Lung Transplant Service
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. Using the HLAMatchmaker algorithm, the authors show that total Class II eplet mismatch is a significant predictor of restrictive allograft syndrome but not bronchiolitis obliterans syndrome in chronic lung allograft dysfunction.
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