Use of donor-derived-cell-free DNA as a marker of early allograft injury in primary graft dysfunction (PGD) to predict the risk of chronic lung allograft dysfunction (CLAD).
Use of donor-derived-cell-free DNA as a marker of early allograft injury in primary graft dysfunction (PGD) to predict the risk of chronic lung allograft dysfunction (CLAD).
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DOI：
10.1016/j.healun.2021.02.008
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发表时间：
2021-06
期刊：
影响因子：
--
通讯作者：
Agbor-Enoh S
中科院分区：
文献类型：
--
作者：
Keller M;Bush E;Diamond JM;Shah P;Matthew J;Brown AW;Sun J;Timofte I;Kong H;Tunc I;Luikart H;Iacono A;Nathan SD;Khush KK;Orens J;Jang M;Agbor-Enoh S
原发性移植物功能障碍（PGD）是慢性同种异体肺功能障碍（CLAD）的危险因素。然而，PGD和同种异体移植物损伤程度之间的关系仍然不明确。在这项研究中，我们利用一种新的同种异体移植物损伤的生物标志物，供体来源的细胞游离DNA百分比（%ddcfDNA），研究PGD，同种异体移植物损伤程度和CLAD的发展之间的关联。该前瞻性队列研究招募了99名肺移植受者，并在第1、3和7天收集血浆样品用于%ddcfDNA测量。第3天的临床数据用于判定PGD。比较PGD等级之间的%ddcfDNA水平。在PGD患者中，比较了发生CLAD的患者和未发生CLAD的患者之间的%ddcfDNA。在移植后第3天，PGD患者的%ddcfDNA高于非PGD患者（中位数（IQR）：12.2%（8.2，22.0）vs 8.5%（5.6，13.2）p = 0.01）。%ddcfDNA与PGD的严重程度等级相关（r = 0.24，p = 0.02）。在PGD组中，较高水平的%ddcfDNA与发生CLAD的风险增加相关（log OR（SE）1.38（0.53），p=0.009）。发生CLAD的PGD患者的%ddcfDNA水平比未发生CLAD的患者高约2倍（中位数（IQR）：22.4%（11.8，27.6）vs. 9.9%（6.7，14.9），p = 0.007）。与非PGD患者相比，PGD患者表现出增加的早期移植后同种异体移植物损伤，如通过%ddcfDNA测量的，并且这些高%ddcfDNA水平与CLAD的后续发展相关。该研究表明，%ddcfDNA鉴定PGD患者的CLAD风险高于单独的PGD。
Primary Graft Dysfunction (PGD) is a risk factor for Chronic Lung Allograft Dysfunction (CLAD). However, the association between PGD and degree of allograft injury remains poorly defined. In this study, we leverage a novel biomarker for allograft injury, percentage donor-derived cell-free DNA (%ddcfDNA), to study the association between PGD, degree of allograft injury, and the development of CLAD. This prospective cohort study recruited 99 lung transplant recipients and collected plasma samples on days 1, 3 and 7 for %ddcfDNA measurements. Clinical data on day 3 was used to adjudicate for PGD. %ddcfDNA levels were compared between PGD grades. In PGD patients, %ddcfDNA was compared between those who developed CLAD and those who did not. On post-transplant day 3, %ddcfDNA was higher in PGD than in non PGD patients (median (IQR): 12.2% (8.2, 22.0) vs 8.5% (5.6, 13.2) p = 0.01). %ddcfDNA correlated with the severity grade of PGD (r = 0.24, p = 0.02). Within the PGD group, higher levels of %ddcfDNA correlated with increased risk of developing CLAD (log OR(SE) 1.38 (0.53), p=0.009). PGD patients who developed CLAD showed ~2 times higher %ddcfDNA levels than patients who did not develop CLAD (median (IQR): 22.4% (11.8, 27.6) vs. 9.9% (6.7, 14.9), p = 0.007). PGD patients demonstrated increased early post-transplant allograft injury, as measured by %ddcfDNA, in comparison to non PGD patients, and these high %ddcfDNA levels were associated with subsequent development of CLAD. This study suggests that %ddcfDNA identifies PGD patients at greater risk of CLAD than PGD alone.
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DOI：
10.4049/jimmunol.181.8.5738
发表时间：
2008-10-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Iwata T;Philipovskiy A;Fisher AJ;Presson RG Jr;Chiyo M;Lee J;Mickler E;Smith GN;Petrache I;Brand DB;Burlingham WJ;Gopalakrishnan B;Greenspan DS;Christie JD;Wilkes DS
通讯作者：
Wilkes DS
影响因子：
4.4
作者：
Goers, Trudie A.;Ramachandran, Sabarinathan;Mohanakumar, Thalachallour
通讯作者：
Mohanakumar, Thalachallour
影响因子：
4.6
作者：
Tanaka, Shin;Sugimoto, Seiichiro;Toyooka, Shinichi
通讯作者：
Toyooka, Shinichi
影响因子：
6.2
作者：
Bharat, Ankit;Narayanan, Kishore;Mohanakumar, Thalachallour
通讯作者：
Mohanakumar, Thalachallour
影响因子：
4.6
作者：
Fiser, SM;Tribble, CG;Kron, IL
通讯作者：
Kron, IL