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

Area of Science:

• Immunogenetics
• Transplantation Immunology
• Genomic Medicine

Background:

• Human leukocyte antigen (HLA) mismatches between donor and recipient are critical in lung transplantation (LTX).
• Eplet mismatches (epMM) arising from HLA mismatches can trigger de-novo donor-specific HLA-antibodies (dnDSA), especially HLA-DQ-dnDSA.

Purpose of the Study:

• To identify specific risk factors associated with the development of HLA-DQ-dnDSA in lung transplant recipients.
• To evaluate the clinical impact of HLA-DQ-dnDSA on acute cellular rejection (ACR), chronic lung allograft dysfunction (CLAD), and patient survival.

Main Methods:

• Retrospective analysis of 183 LTX patients (2012-2020) with 11-loci HLA typing.
• Calculation of eplet mismatches (epMM) using HLAMatchmaker software.
• Monitoring of dnDSA development within 1-year post-LTX, with statistical comparisons using Chi2-test, Student's t-test, Kaplan-Meier curves, and multivariate Cox regression.

Main Results:

• 22.9% of patients developed HLA-DQ-dnDSA.
• HLA-DQ-homozygous recipients had a significantly higher risk of developing HLA-DQ-dnDSA (p=0.03).
• Specific DQ-eplet combinations and HLA-DQB1*03:01 in homozygous recipients were associated with increased HLA-DQ-dnDSA risk, which correlated with higher rates of ACR and CLAD.

Conclusions:

• HLA-DQ-homozygosity and specific high-risk DQ-epMM are significant predictors of HLA-DQ-dnDSA development in LTX.
• HLA-DQ-dnDSA development negatively impacts graft outcomes, increasing ACR and CLAD.
• Incorporating these findings into clinical practice can enhance immunological compatibility and improve LTX graft outcomes.