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HLA-DPB1 molecular mismatches are risk factors for acute rejection and low 5-year graft function in first kidney

Renato de Marco1, Lúcio R Requião-Moura2, Tamiris R F Raimundo1

  • 1Instituto de Imunogenética (IGEN), Associação Fundo de Incentivo à Pesquisa (AFIP), São Paulo, Brazil.

HLA
|December 3, 2022
PubMed

Insights

Investigating HLA-DPB1 mismatches in kidney transplants revealed specific molecular mismatches (mMM) are linked to acute rejection (AR). However, no direct link was found for low 5-year graft function (5Y-GF) across all recipients.

Area of Science:

  • Immunogenetics
  • Transplantation immunology
  • Nephrology

Background:

  • Human Leukocyte Antigen (HLA) compatibility is crucial for kidney transplant (KT) success.
  • HLA-DPB1 mismatches, particularly molecular mismatches (mMM), are increasingly recognized as potential risk factors.
  • Understanding these mMM impacts on early and long-term outcomes is vital for optimizing KT protocols.

Purpose of the Study:

  • To evaluate the association between HLA-DPB1 allelic and various molecular mismatches (mMM) and the occurrence of acute rejection (AR).
  • To assess the impact of HLA-DPB1 allelic and mMM on 5-year graft function (5Y-GF) in first KT recipients.
  • To identify specific HLA-DPB1 mMM that independently predict AR and impaired graft function.

Main Methods:

  • Retrospective analysis of 130 first deceased donor KT recipients transplanted between 2014-2016.
  • Evaluation of HLA-DPB1 allelic mismatches and multiple mMM types: expression, T cell epitope (TCE), epitope (EMM), eplet (EpMM), antibody-verified eplet (AbVer EpMM), and solvent accessible amino acid (SAMM).
  • Cox and logistic regression analyses were used to determine independent associations with AR and 5Y-GF.

Main Results:

  • No association was found between HLA-DPB1 allelic mismatches and AR or 5Y-GF.
  • High donor creatinine, non-permissive TCE MM, ABCDEF EMM load ≥6, EpMM load ≥6, SAMM load ≥5, and AbVer EpMM load ≥3 were independently associated with AR.
  • No HLA-DPB1 mMM were associated with 5Y-GF in the overall cohort.
  • In a subgroup excluding expanded criteria donors, AbVerEpMM load ≥2, SAMM load ≥7, cerebro-vascular death, and donor age were associated with AR and low 5Y-GF.

Conclusions:

  • Specific HLA-DPB1 molecular mismatches, not allelic mismatches, are associated with acute rejection in first kidney transplant recipients.
  • Certain HLA-DPB1 mMM show associations with both acute rejection and impaired 5-year graft function when expanded criteria donors are excluded.
  • This study highlights the importance of detailed HLA-DPB1 molecular mismatch analysis for predicting kidney transplant outcomes.
Keywords:
HLA-DPB1acute rejectionepitope matchingmolecular mismatchesrenal transplantation

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