Low Hydrophobic Mismatch Scores Calculated for HLA-A/B/DR/DQ Loci Improve Kidney Allograft Survival

Front Immunol. 2020 Oct 29:11:580752. doi: 10.3389/fimmu.2020.580752. eCollection 2020.


We evaluated the impact of human leukocyte antigen (HLA) disparity (immunogenicity; IM) on long-term kidney allograft survival. The IM was quantified based on physicochemical properties of the polymorphic linear donor/recipient HLA amino acids (the Cambridge algorithm) as a hydrophobic, electrostatic, amino acid mismatch scores (HMS\AMS\EMS) or eplet mismatch (EpMM) load. High-resolution HLA-A/B/DRB1/DQB1 types were imputed to calculate HMS for primary/re-transplant recipients of deceased donor transplants. The multiple Cox regression showed the association of HMS with graft survival and other confounders. The HMS integer 0-10 scale showed the most survival benefit between HMS 0 and 3. The Kaplan-Meier analysis showed that: the HMS=0 group had 18.1-year median graft survival, a 5-year benefit over HMS>0 group; HMS ≤ 3.0 had 16.7-year graft survival, a 3.8-year better than HMS>3.0 group; and, HMS ≤ 7.8 had 14.3-year grafts survival, a 1.8-year improvement over HMS>7.8 group. Stratification based on EMS, AMS or EpMM produced similar results. Additionally, the importance of HLA-DR with/without -DQ IM for graft survival was shown. In our simulation of 1,000 random donor/recipient pairs, 75% with HMS>3.0 were re-matched into HMS ≤ 3.0 and the remaining 25% into HMS≥7.8: after re-matching, the 13.5 years graft survival would increase to 16.3 years. This approach matches donors to recipients with low/medium IM donors thus preventing transplants with high IM donors.

Keywords: HLA mismatch; human leukocyte antigen (HLA); immunogenicity; kidney allocation; kidney transplantation; transplant survival.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Allografts
  • Amino Acids / chemistry
  • Amino Acids / genetics
  • Female
  • Genetic Loci
  • Graft Rejection / immunology*
  • Graft Survival
  • HLA-A Antigens / genetics*
  • HLA-A Antigens / metabolism
  • HLA-B Antigens / genetics*
  • HLA-B Antigens / metabolism
  • HLA-DQ Antigens / genetics*
  • HLA-DQ Antigens / metabolism
  • HLA-DR Antigens / genetics*
  • HLA-DR Antigens / metabolism
  • Histocompatibility Testing
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Resource Allocation
  • Survival Analysis
  • Tissue Donors
  • Transplant Recipients
  • Young Adult


  • Amino Acids
  • HLA-A Antigens
  • HLA-B Antigens
  • HLA-DQ Antigens
  • HLA-DR Antigens