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Identification of risk epitope mismatches associated with de novo donor‐specific HLA antibody development in cardiothoracic transplantation
Author(s) -
McCaughan J. A.,
Battle R. K.,
Singh S. K. S.,
Tikkanen J. M.,
Moayedi Y.,
Ross H. J.,
Singer L. G.,
Keshavjee S.,
Tinckam K. J.
Publication year - 2018
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.14951
Subject(s) - medicine , human leukocyte antigen , epitope , immunogenicity , transplantation , immunology , antibody , lung transplantation , histocompatibility testing , antigen
The development of de novo donor‐specific HLA antibodies (dn DSA ) after transplantation is associated with graft failure, mortality, and cost. There is no effective therapeutic intervention to prevent dn DSA or ameliorate associated injury. The aims of this study were to identify specific HLA factors associated with dn DSA development and to propose primary prevention strategies that could reduce the incidence of dn DSA without prohibitively limiting access to transplant. The investigation cohort included heart transplant recipients from 2008 to 2015 (n = 265). HLA typing was performed and HLA antibody testing was undertaken before and after transplantation. HLA Matchmaker analysis was performed for persistent dn DSA to identify potentially more immunogenic eplet differences. Validation was performed in recipients of lung transplants from 2008 to 2013 (n = 433). The majority of recipients with dn DSA had antibodies to identical eplet positions on DQ 2 and DQ 7. A high‐risk epitope mismatch (found in DQA 1*05 + DQB 1*02/ DQB 1*03:01(7)) was associated with a 4.2‐ and 4.9‐fold increased risk of dn DSA in heart and lung recipients respectively. HLA electrostatic potential modeling provided a plausible explanation for this observed immunogenicity. A theoretical allocation algorithm avoiding high‐risk epitope mismatches was generated and predicted to reduce dn DSA by up to 72% without additional testing, eplet analysis, or cost.