Donor-derived cell-free DNA is associated with cardiac allograft vasculopathy.

Donor-derived cell-free DNA is associated with cardiac allograft vasculopathy.
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DOI:
10.1111/ctr.14206
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发表时间:
2021-03
影响因子:
2.1
通讯作者:
--
中科院分区:
医学3区
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供体来源的细胞游离DNA(dd-cfDNA)在心脏移植物血管病变(CAV)筛查中的作用尚不清楚。我们假设dd-cfDNA与稳定的心脏移植(HT)受者中的CAV、炎症标志物和血管生成相关。将65例移植后≥2年、近期无排斥反应的HT受体按高dd-cfDNA水平(≥0.12%)与低dd-cfDNA水平(<0.12%)分层。靶向扩增、下一代测序测定(AlloSure®; CareDx,Inc.)用于检测dd-cfDNA。使用多重免疫测定系统(Bioplex®)评估外周血炎症和血管生成标志物。在65例患者中,58例患者具有已知的CAV状态并被纳入。30例患者的dd-cfDNA水平较高(≥0.12%),28例患者的dd-cfDNA水平较低(<0.12%)。CAV存在于63%的具有高dd-cfDNA的患者中,而具有低dd-cfDNA的患者中为35%(p = .047)ddd-cfDNA高的患者中为25%,而具有低dd-cfDNA的患者中为3.8%(p = .03)。在排斥反应、炎症或血管生成标志物方面没有差异。重要的是,当按移植后时间分层时,dd-cfDNA水平没有差异。在稳定的慢性HT接受者中,较高的dd-cfDNA水平与CAV相关。进一步的研究是必要的,以调查dd-cfDNA水平和CAV严重程度之间的可能关联,以及dd-cfDNA是否可以预测CAV进展。
The role of donor-derived cell-free DNA (dd-cfDNA) in screening for cardiac allograft vasculopathy (CAV) is unknown. We hypothesized that dd-cfDNA correlates with CAV, markers of inflammation, and angiogenesis in stable heart transplant (HT) recipients. Sixty-five HT recipients ≥2 years post-transplant, without recent rejection, were stratified by high (≥0.12%) versus low levels (<0.12%) of dd-cfDNA. A targeted amplification, next-generation sequencing assay (AlloSure®; CareDx, Inc.) was used to detect dd-cfDNA. Peripheral blood inflammatory and angiogenesis markers were assessed using a multiplex immunoassay system (Bioplex®). Of 65 patients, 58 patients had a known CAV status and were included. Thirty had high levels of dd-cfDNA (≥0.12%), and 28 had low levels (<0.12%). CAV was present in 63% of patients with high dd-cfDNA vs. 35% with low dd-cfDNA (p = .047).Donor-specific antibodies were present in 25% of patients with high dd-cfDNA vs. 3.8% in those with low dd-cfDNA (p = .03). There were no differences in rejection episodes, inflammatory, or angiogenesis markers. Importantly, dd-cfDNA levels were not different when stratified by time post-transplant. Higher dd-cfDNA levels were associated with CAV in stable chronic HT recipients. Further studies are warranted to investigate a possible association between dd-cfDNA levels and CAV severity and whether dd-cfDNA can predict CAV progression.
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