Assessment of dd-cfDNA Levels in Clinically Stable Lung Allograft Recipients Beyond the Initial 2 y Posttransplant.
Assessment of dd-cfDNA Levels in Clinically Stable Lung Allograft Recipients Beyond the Initial 2 y Posttransplant.
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DOI：
10.1097/txd.0000000000001411
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发表时间：
2022-12
影响因子：
2.3
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中科院分区：
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供体来源的细胞游离DNA（dd-cfDNA）是肺移植后1 - 2年内诊断急性同种异体移植物损伤的有用生物标志物，但其诊断慢性肺移植物功能障碍（CLAD）的效用尚未研究。了解移植后最初2年之后的基线dd-cfDNA动力学是确定dd-cfDNA作为CLAD生物标志物的效用的必要的第一步。我们试图在移植后>2年的临床稳定的肺同种异体移植受者中建立基线dd-cfDNA%水平。我们进行了一项前瞻性、单中心、观察性研究，以确定移植后>2年临床稳定的肺同种异体移植受者的血浆dd-cfDNA水平。入组了51例受试者，在中位252天内获得了≥3次基线dd-cfDNA测量值。我们队列中的中位基线百分比dd-cfDNA水平为0.45%（四分位距[IQR]，0.26-0.69）。基于移植后持续时间，dd-cfDNA存在统计学显著差异（移植后≤5年中位数0.41% [IQR，0.21-0.64] vs>5年移植后中位数0.50% [IQR，0.33-0.76]; P < 0.02）。然而，dd-cfDNA的这种微小变化的临床意义尚不确定，因为这种变化幅度在73%的生物试验变异范围内。该研究首次定义了肺移植后>2年的临床稳定患者中dd-cfDNA的水平。这些发现为dd-cfDNA作为CLAD的可能生物标志物的研究奠定了基础。
Donor-derived cell-free DNA (dd-cfDNA) is a useful biomarker for the diagnosis of acute allograft injury within the first 1 to 2 y after lung transplant, but its utility for diagnosing chronic lung allograft dysfunction (CLAD) has not yet been studied. Understanding baseline dd-cfDNA kinetics beyond the initial 2 y posttransplant is a necessary first step in determining the utility of dd-cfDNA as a CLAD biomarker. We seek to establish baseline dd-cfDNA% levels in clinically stable lung allograft recipients who are >2 y posttransplant. We performed a prospective, single-center, observational study to identify plasma dd-cfDNA levels in clinically stable lung allograft recipients >2 y posttransplant. Fifty-one subjects were enrolled and ≥3 baseline dd-cfDNA measurements were acquired during a median of 252 d. The median baseline percent dd-cfDNA level in our cohort was 0.45% (interquartile range [IQR], 0.26–0.69). There were statistically significant differences in dd-cfDNA based on posttransplant duration (≤5 y posttransplant median 0.41% [IQR, 0.21–0.64] versus >5 y posttransplant median 0.50% [IQR, 0.33–0.76]; P < 0.02). However, the clinical significance of this small change in dd-cfDNA is uncertain because this magnitude of change is within the biologic test variation of 73%. This study is the first to define levels of dd-cfDNA in clinically stable patients who are >2 y post–lung transplant. These findings lay the groundwork for the study of dd-cfDNA as a possible biomarker for CLAD.