Department of Lung Transplantation, St Vincent's Hospital Darlinghurst, Sydney, Australia.
Stats Central, Mark Wainwright Analytical Centre, University of New South Wales, Sydney, Australia.
Am J Transplant. 2023 Jul;23(7):1009-1021. doi: 10.1016/j.ajt.2023.04.004. Epub 2023 Apr 11.
A high-risk epitope mismatch (REM) (found in DQA1∗05 + DQB1∗02/DQB1∗03:01) is associated with de novo donor specific antibodies after lung transplantation (LTx). Chronic lung allograft dysfunction (CLAD) remains a barrier to LTx survival. This study aimed to measure the association between DQ REM and the risk of CLAD and death after LTx. A retrospective analysis of LTx recipients at a single center was conducted between January 2014 and April 2019. Molecular typing at human leucocyte antigen-DQA/DQB identified DQ REM. Multivariable competing risk and Cox regression models were used to measure the association between DQ REM, time-to-CLAD, and time-to-death. DQ REM was detected in 96/268 (35.8%), and DQ REM de novo donor specific antibodies were detected in 34/96 (35.4%). CLAD occurred in 78 (29.1%), and 98 (36.6%) recipients died during follow-up. When analyzed as a baseline predictor, DQ REM status was associated with CLAD (subdistribution hazard ratio (SHR), 2.19; 95% confidence interval [CI], 1.40-3.43; P = .001). After adjustment for time-dependent variables, DQ REM dn-DSA (SHR, 2.43; 95% CI, 1.10-5.38; P = .029) and A-grade rejection score (SHR, 1.22; 95% CI, 1.11-1.35; P = <.001), DQ REM status was not independently associated with CLAD. DQ REM was not associated with death (hazard ratio, 1.18; 95% CI, 0.72-1.93; P = .51). Classification of DQ REM may identify patients at risk of poor outcomes and should be incorporated into clinical decision-making.
高风险表位错配（REM）（存在于 DQA1∗05 + DQB1∗02/DQB1∗03:01 中）与肺移植（LTx）后新出现的供体特异性抗体有关。慢性肺移植物功能障碍（CLAD）仍然是 LTx 存活的障碍。本研究旨在测量 DQ REM 与 LTx 后 CLAD 和死亡风险之间的关联。对 2014 年 1 月至 2019 年 4 月在一家中心接受 LTx 的患者进行了回顾性分析。人类白细胞抗原-DQA/DQB 的分子分型确定了 DQ REM。多变量竞争风险和 Cox 回归模型用于测量 DQ REM、CLAD 时间和死亡时间之间的关联。在 268 例中检测到 96 例（35.8%）DQ REM，在 34 例中检测到 96 例（35.4%）DQ REM 新出现的供体特异性抗体。CLAD 发生在 78 例（29.1%），98 例（36.6%）患者在随访期间死亡。当作为基线预测因子进行分析时，DQ REM 状态与 CLAD 相关（亚分布风险比（SHR），2.19；95%置信区间[CI]，1.40-3.43；P =.001）。调整时间依赖性变量后，DQ REM dn-DSA（SHR，2.43；95%CI，1.10-5.38；P =.029）和 A 级排斥评分（SHR，1.22；95%CI，1.11-1.35；P = <.001），DQ REM 状态与 CLAD 无独立相关性。DQ REM 与死亡无关（风险比，1.18；95%CI，0.72-1.93；P =.51）。DQ REM 的分类可能会识别出预后不良的患者，应将其纳入临床决策。
