Korean J Transplant.  2022 Nov;36(Supple 1):S147. 10.4285/ATW2022.F-2652.

Comparison of immunogenicity among each human leukocyte antigen DQ mismatches for the development of de novo donor specific antibodies in Thai kidney transplant recipients

• Skulratanasak P
• Larpparisuth N
• Luxsananun, T
• Premasathian N
• Vongwiwatana A

• KMID: 2535663
• DOI: http://doi.org/10.4285/ATW2022.F-2652

Abstract

Background
Human leukocyte antigen (HLA) mismatches are associated with the development of de novo donor-specific antibodies (dnDSA) which can lead to premature allograft failure. HLA-DQ antibodies are the most common (dnDSA) after kidney transplantation (KT). However, each HLA-DQ mismatch might have the unequal immunologic risk and different impact on graft outcomes.
Methods
We performed retrospective analysis in KT recipients with HLA-DQB1 mismatches at Siriraj hospital between January 2006 and December 2020. Our center performed routine post-KT dnDSA surveillance annually. The prevalence and associated risk factors for the development of dnDSA against each HLA-DQB1 was determined. Effect of dnDSA to late rejection and graft survival was also observed.
Results
During the median follow-up time of 6.4 years, 59 of 491 (12.02%) recipients developed dnDSA to HLA-DQB1 with median time 4.2 years after KT. The patients who had dnDSA were younger (P=0.009), pre-KT PRA >20% (P=0.044), non-tacrolimus immunosuppression (P<0.001) and non-adherence (P=0.031). Risk for dnDSA occurrence is significantly higher in recipients who had HLA-DQ7 (hazard ratio [HR], 2.8; 95% confidence interval [CI], 1.21–6.52; P=0.017) and HLA-DQ9 (HR, 2.63; 95% CI, 1.11–6.27, P=0.028), respectively. Recipients who developed dnDSA to HLA-DQ had significantly higher incidence of late allograft rejection (HR, 7.76; 95% CI, 5–12.03; P<0.0001) and had lower 10-year allograft survival compared with whom without dnDSA (70.2% and 87.8%; P=0.001).
Conclusions
Antibodies against HLA-DQB1 significantly increase risk of allograft rejection and unfavorable graft survival. All HLA-DQ mismatches do not express the same immunogenicity for triggering antibodies formation. Patients with HLA-DQ7 and subsequently HLA-DQ9 mismatch have the greatest risk for dnDSA occurrence. Kidney allocation and individualized immunosup-pressive adjustment based on each HLA-DQ mismatches will improve the long-term graft survival.