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HLA Matching at the Eplet Level Protects Against Chronic Lung Allograft Dysfunction
Author(s) -
Walton D. C.,
Hiho S. J.,
Cantwell L. S.,
Diviney M. B.,
Wright S. T.,
Snell G. I.,
Paraskeva M. A.,
Westall G. P.
Publication year - 2016
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.13798
Subject(s) - medicine , hazard ratio , confidence interval , bronchiolitis obliterans , human leukocyte antigen , transplantation , lung transplantation , gastroenterology , immunology , antigen
Donor selection in lung transplantation ( LT x) 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 LT x undertaken at the Alfred Hospital between 2008 and 2012 met criteria. Post‐ LT x 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 HLAM atchmaker, eplet mismatches between each donor/recipient pairing were analyzed and correlated against incidences of CLAD . HLA ‐ DRB 1/3/4/5+ 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 ‐ DRB 1/3/4/5 + 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 LT x.