A high-risk HLA-DQ allele combination (HLA-DQ1 homozygous recipients with HLA-DQ3/DQ1 donors) significantly increased the risk of developing de novo donor-specific HLA-DQ antibodies after lung transplantation (HR 6.17).
Cohort (n=183)
No
Do high-risk HLA-DQ mismatches increase the development of HLA-DQ-dnDSA and adverse clinical outcomes in lung transplant recipients?
High-risk HLA-DQ mismatches and HLA-DQ homozygosity increase the risk of developing de novo donor-specific antibodies, which are associated with acute cellular rejection and chronic lung allograft dysfunction after lung transplantation.
Hazard Ratio: 6.17
Absolute Event Rate: 81.8% vs 19.2%
p-value: p=<0.0001
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 et al. (Thu,) conducted a cohort in Lung transplantation (n=183). High-risk HLA-DQ allele combination (HLA-DQ1 homozygous recipient with HLA-DQ3/DQ1 donor) vs. Other HLA-DQ allele combinations was evaluated on Development of HLA-DQ-dnDSA (HR 6.17, p=<0.0001). A high-risk HLA-DQ allele combination (HLA-DQ1 homozygous recipients with HLA-DQ3/DQ1 donors) significantly increased the risk of developing de novo donor-specific HLA-DQ antibodies after lung transplantation (HR 6.17).