Chou-Wu Elaine, Niemann Matthias, Youngs Danny, Gimferrer Idoia
Immunogenetics/HLA Laboratory, Bloodworks Northwest, Seattle, WA, United States.
PIRCHE AG, Berlin, Germany.
Front Immunol. 2025 Feb 25;16:1508796. doi: 10.3389/fimmu.2025.1508796. eCollection 2025.
The presence of donor-specific antibody (dnDSA) has detrimental effect on allograft outcomes in kidney transplantation. As humoral responses in transplantation are elicited targeting non-self-epitopes on donor HLA proteins, assessing HLA mismatches at the molecular level provides a refined means for immunological risk stratification.
In the present study, we utilized three HLA molecular mismatch assessment algorithms, Snow, HLAMatchmaker, and PIRCHE-II, to evaluate the independent and synergistic association of B cell and T cell epitope mismatches with dnDSA development in a cohort of 843 kidney transplant recipients.
Our results demonstrated that B cell and T cell epitope mismatches at HLA Class I and DRB1/DQB1 loci are remarkably increased in dnDSA-positive recipients, even after normalization by allele mismatch numbers in individual study subjects. Furthermore, elevated Snow, verified eplet mismatches, and PIRCHE-II scores are significantly associated with dnDSA occurrence individually and in combination.
Our findings highlight the value of utilizing B cell and T cell epitope mismatch evaluation in living donor selection and immunological risk stratification to improve transplant outcomes.
供体特异性抗体（dnDSA）的存在对肾移植中同种异体移植物的预后有不利影响。由于移植中的体液反应是针对供体HLA蛋白上的非自身表位引发的，在分子水平评估HLA错配为免疫风险分层提供了一种精细的方法。
在本研究中，我们使用了三种HLA分子错配评估算法，即Snow、HLAMatchmaker和PIRCHE-II，来评估843名肾移植受者队列中B细胞和T细胞表位错配与dnDSA发生之间的独立和协同关联。
我们的结果表明，即使在个体研究对象中按等位基因错配数进行标准化后，dnDSA阳性受者中HLA I类和DRB1/DQB1位点的B细胞和T细胞表位错配也显著增加。此外，升高的Snow、验证的表位错配和PIRCHE-II评分分别或联合起来与dnDSA的发生显著相关。
我们的研究结果突出了在活体供体选择和免疫风险分层中利用B细胞和T细胞表位错配评估以改善移植预后的价值。
