Science and Research

High-Risk HLA-DQ Mismatches Are Associated With Adverse Outcomes After Lung Transplantation

Human leukocyte antigen (HLA) mismatches (MM) between donor and recipient lead to eplet MM (epMM) in lung transplantation (LTX), which can induce the development of de-novo donor-specific HLA-antibodies (dnDSA), particularly HLA-DQ-dnDSA. Aim of our study was to identify risk factors for HLA-DQ-dnDSA development. We included all patients undergoing LTX between 2012 and 2020. All recipients/donors were typed for HLA 11-loci. Development of dnDSA was monitored 1-year post-LTX. EpMM were calculated using HLAMatchmaker. Differences in proportions and means were compared using Chi2-test and Students' t-test. We used Kaplan-Meier curves with LogRank test and multivariate Cox regression to compare acute cellular rejection (ACR), chronic lung allograft dysfunction (CLAD) and survival. Out of 183 patients, 22.9% patients developed HLA-DQ-dnDSA. HLA-DQ-homozygous patients were more likely to develop HLA-DQ-dnDSA than HLA-DQ-heterozygous patients (p = 0.03). Patients homozygous for HLA-DQ1 appeared to have a higher risk of developing HLA-DQ-dnDSA if they received a donor with HLA-DQB1*03:01. Several DQ-eplets were significantly associated with HLA-DQ-dnDSA development. In the multivariate analysis HLA-DQ-dnDSA was significantly associated with ACR (p = 0.03) and CLAD (p = 0.01). HLA-DQ-homozygosity, several high-risk DQ combinations and high-risk epMM result in a higher risk for HLA-DQ-dnDSA development which negatively impact clinical outcomes. Implementation in clinical practice could improve immunological compatibility and graft outcomes.

  • Kleid, L.
  • Walter, J.
  • Moehnle, P.
  • Wichmann, C.
  • Kovács, J.
  • Humpe, A.
  • Schneider, C.
  • Michel, S.
  • Kneidinger, N.
  • Irlbeck, M.
  • Fertmann, J.
  • Dick, A.
  • Kauke, T.

Keywords

  • Humans
  • *Lung Transplantation/adverse effects
  • Female
  • Male
  • *HLA-DQ Antigens/immunology/genetics
  • Middle Aged
  • Adult
  • *Graft Rejection/immunology
  • Risk Factors
  • Histocompatibility Testing
  • Retrospective Studies
  • Tissue Donors
  • Isoantibodies/immunology
  • Graft Survival/immunology
  • HLA-DQ antibody
  • de novo donor specific antibody
  • eplet matching
  • lung transplantation
  • risk-stratification
Publication details
DOI: 10.3389/ti.2024.13010
Journal: Transpl Int
Pages: 13010 
Work Type: Original
Location: CPC-M
Disease Area: ROR
Partner / Member: HMGU, KUM
Access-Number: 39381015

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