Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada; Department of Immunology, University of Manitoba, Winnipeg, Manitoba, Canada; Shared Health Services Manitoba, Winnipeg, Manitoba, Canada.
George and Fay Yee Centre for Healthcare Innovation, University of Manitoba, Winnipeg, Manitoba, Canada.
Am J Transplant. 2023 Dec;23(12):1882-1892. doi: 10.1016/j.ajt.2023.07.025. Epub 2023 Aug 4.
De novo donor-specific antibody (dnDSA) after renal transplantation has been shown to correlate with antibody-mediated rejection and allograft loss. However, the lack of proven interventions and the time and cost associated with annual screening for dnDSA are difficult to justify for all recipients. We studied a well-characterized consecutive cohort (n = 949) with over 15 years of prospective dnDSA surveillance to identify risk factors that would help institute a resource-responsible surveillance strategy. Younger recipient age and HLA-DR/DQ molecular mismatch were independent predictors of dnDSA development. Combining both risk factors into recipient age molecular mismatch categories, we found that 52% of recipients could be categorized as low-risk for dnDSA development (median subclinical dnDSA-free survival at 5 and 10 years, 98% and 97%, respectively). After adjustment, multivariate correlates of dnDSA development included tacrolimus versus cyclosporin maintenance immunosuppression (hazard ratio [HR], 0.37; 95% CI, 0.2-0.6; P < .0001) and recipient age molecular mismatch category: intermediate versus low (HR, 2.48; 95% CI, 1.5-4.2; P = .0007), high versus intermediate (HR, 2.56; 95% CI, 1.6-4.2; P = .0002), and high versus low (HR, 6.36; 95% CI, 3.7-10.8; P < .00001). When combined, recipient age and HLA-DR/DQ molecular mismatch provide a novel data-driven approach to reduce testing by >50% while selecting those most likely to benefit from dnDSA surveillance.
肾移植后新出现的供体特异性抗体（dnDSA）已被证明与抗体介导的排斥反应和移植物丢失相关。然而，缺乏经过验证的干预措施，以及每年筛查 dnDSA 相关的时间和成本，使得所有受者都难以接受。我们研究了一个特征明确的连续队列（n=949），该队列进行了超过 15 年的前瞻性 dnDSA 监测，以确定有助于建立资源负责的监测策略的风险因素。受者年龄较小和 HLA-DR/DQ 分子错配是 dnDSA 发展的独立预测因素。将这两个风险因素结合到受者年龄分子错配类别中，我们发现 52%的受者可以归类为 dnDSA 发展的低风险（中位数亚临床 dnDSA 无复发生存率在 5 年和 10 年分别为 98%和 97%）。调整后，dnDSA 发展的多变量相关因素包括他克莫司与环孢素维持免疫抑制（风险比 [HR]，0.37；95%置信区间，0.2-0.6；P<.0001）和受者年龄分子错配类别：中危与低危（HR，2.48；95%置信区间，1.5-4.2；P=0.0007），高危与中危（HR，2.56；95%置信区间，1.6-4.2；P=0.0002），高危与低危（HR，6.36；95%置信区间，3.7-10.8；P<.00001）。当两者结合时，受者年龄和 HLA-DR/DQ 分子错配为减少检测提供了一种新颖的基于数据的方法，可将检测减少超过 50%，同时选择最有可能从 dnDSA 监测中获益的受者。
