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

AI Article Synopsis

  • The study assessed how disparities in human leukocyte antigen (HLA) affect the long-term survival of kidney transplants by quantifying immunogenicity (IM) through various scoring methods.
  • Results indicated that a lower HLA mismatch score (HMS) correlated with improved graft survival, with significant survival benefits observed for HMS values between 0 and 3.
  • Simulation data suggested that re-matching donor/recipient pairs with low to medium IM could enhance median graft survival from 13.5 years to 16.3 years, emphasizing the importance of HLA-DR distinctions.

Article Abstract

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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7659444PMC
http://dx.doi.org/10.3389/fimmu.2020.580752DOI Listing

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