Class II HLA epitope matching-A strategy to minimize de novo donor-specific antibody development and improve outcomes

Am J Transplant. 2013 Dec;13(12):3114-22. doi: 10.1111/ajt.12478. Epub 2013 Oct 25.


De novo donor-specific antibody (dnDSA) develops in 15-25% of renal transplant recipients within 5 years of transplantation and is associated with 40% lower graft survival at 10 years. HLA epitope matching is a novel strategy that may minimize dnDSA development. HLAMatchmaker software was used to characterize epitope mismatches at 395 potential HLA-DR/DQ/DP conformational epitopes for 286 donor-recipient pairs. Epitope specificities were assigned using single antigen HLA bead analysis and correlated with known monoclonal alloantibody epitope targets. Locus-specific epitope mismatches were more numerous in patients who developed HLA-DR dnDSA alone (21.4 vs. 13.2, p < 0.02) or HLA-DQ dnDSA alone (27.5 vs. 17.3, p < 0.001). An optimal threshold for epitope mismatches (10 for HLA-DR, 17 for HLA-DQ) was defined that was associated with minimal development of Class II dnDSA. Applying these thresholds, zero and 2.7% of patients developed dnDSA against HLA-DR and HLA-DQ, respectively, after a median of 6.9 years. Epitope specificity analysis revealed that 3 HLA-DR and 3 HLA-DQ epitopes were independent multivariate predictors of Class II dnDSA. HLA-DR and DQ epitope matching outperforms traditional low-resolution antigen-based matching and has the potential to minimize the risk of de novo Class II DSA development, thereby improving long-term graft outcome.

Keywords: Antibody-mediated rejection; donor-specific antibody; epitope; kidney transplant.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies / chemistry
  • Antigens / chemistry
  • Cohort Studies
  • Epitopes / chemistry*
  • Graft Rejection / immunology
  • Graft Survival / immunology
  • HLA-DP Antigens / chemistry
  • HLA-DQ Antigens / chemistry
  • HLA-DR Antigens / chemistry
  • Histocompatibility Antigens Class II / chemistry*
  • Histocompatibility Testing
  • Humans
  • Isoantibodies / immunology
  • Kidney / immunology
  • Kidney Transplantation
  • Middle Aged
  • Multivariate Analysis
  • Protein Conformation
  • Risk
  • Tissue Donors
  • Treatment Outcome


  • Antibodies
  • Antigens
  • Epitopes
  • HLA-DP Antigens
  • HLA-DQ Antigens
  • HLA-DR Antigens
  • Histocompatibility Antigens Class II
  • Isoantibodies