Cell-Free DNA Maps Tissue Injury and Correlates with Disease Severity in Lung Transplant Candidates.
Cell-Free DNA Maps Tissue Injury and Correlates with Disease Severity in Lung Transplant Candidates.
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无细胞 DNA 绘制了肺移植候选者的组织损伤图并与疾病严重程度相关。
DOI：
10.1164/rccm.202306-1064oc
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发表时间：
2024
影响因子：
24.7
通讯作者：
Ca
中科院分区：
文献类型：
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作者：
Balasubramanian,Shanti;Richert,MaryE;Kong,Hyesik;Fu,Sheng;Jang,MoonKyoo;Andargie,TemesgenE;Keller,MichaelB;Alnababteh,Muhtadi;Park,Woojin;Apalara,Zainab;Sun,Jian;Redekar,Neelam;Orens,Jonathan;Aryal,Shambhu;Bush,ErrolL;Ca
原理：在许多情况下，血浆游离DNA水平与疾病严重程度相关。Pretransplant cell free DNA may risk stratify lung transplant candidates for post-transplant complications.Objectives：To evaluate if pretransplant cell free DNA levels and tissue sources identify patients at high risk of primary graft dysfunction and other pre-and post-transplant outcomes.Methods：This multicenter，prospective cohort study recruited 186 lung transplant candidates.采集移植前血浆样品以测量游离DNA。进行亚硫酸氢盐测序以鉴定游离DNA的组织来源。多变量回归模型确定了游离DNA水平与原发性移植物功能障碍的主要结局和其他移植结局之间的相关性，包括肺分配评分、慢性肺移植物功能障碍和死亡。（中位数[四分位距]，23.7 ng/ml [15.1-35.6]对比12.9 ng/ml [9.9-18.4];P< 0.0001），主要来源于炎性先天免疫细胞。细胞游离DNA水平和组织来源因原发性肺部疾病类别而异，并与肺部分配评分相关（P< 0.001）。移植前高游离DNA增加原发性移植物功能障碍的风险（比值比，1.60; 95%置信区间[CI]，1.09-2.46;P= 0.0220），和死亡（风险比，1.43; 95% CI，1.07-1.92;P=0.0171），但不是慢性肺移植物功能障碍结论：肺移植候选者表现出高度的组织损伤，伴随升高的细胞游离DNA，主要来源于先天免疫细胞。移植前血浆游离DNA水平可预测移植后并发症
Rationale:Plasma cell-free DNA levels correlate with disease severity in many conditions. Pretransplant cell-free DNA may risk stratify lung transplant candidates for post-transplant complications.Objectives:To evaluate if pretransplant cell-free DNA levels and tissue sources identify patients at high risk of primary graft dysfunction and other pre- and post-transplant outcomes.Methods:This multicenter, prospective cohort study recruited 186 lung transplant candidates. Pretransplant plasma samples were collected to measure cell-free DNA. Bisulfite sequencing was performed to identify the tissue sources of cell-free DNA. Multivariable regression models determined the association between cell-free DNA levels and the primary outcome of primary graft dysfunction and other transplant outcomes, including Lung Allocation Score, chronic lung allograft dysfunction, and death.Measurements and Main Results:Transplant candidates had twofold greater cell-free DNA levels than healthy control patients (median [interquartile range], 23.7 ng/ml [15.1–35.6] vs. 12.9 ng/ml [9.9–18.4];P< 0.0001), primarily originating from inflammatory innate immune cells. Cell-free DNA levels and tissue sources differed by native lung disease category and correlated with the Lung Allocation Score (P< 0.001). High pretransplant cell-free DNA increased the risk of primary graft dysfunction (odds ratio, 1.60; 95% confidence interval [CI], 1.09–2.46;P= 0.0220), and death (hazard ratio, 1.43; 95% CI, 1.07–1.92;P=0.0171) but not chronic lung allograft dysfunction (hazard ratio, 1.37; 95% CI, 0.97–1.94;P=0.0767).Conclusions:Lung transplant candidates demonstrate a heightened degree of tissue injury with elevated cell-free DNA, primarily originating from innate immune cells. Pretransplant plasma cell-free DNA levels predict post-transplant complications.