NOT ALL CELL-FREE MITOCHONDRIAL DNA IS EQUAL IN TRAUMA PATIENTS.
NOT ALL CELL-FREE MITOCHONDRIAL DNA IS EQUAL IN TRAUMA PATIENTS.
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DOI：
10.1097/shk.0000000000001969
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发表时间：
2022-09-01
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线粒体DNA（mtDNA）作为一种促炎性损伤相关的分子模式，通过Toll样受体9刺激先天性免疫激活，类似于细菌DNA。许多临床研究已经测量了创伤患者血浆中游离mtDNA的升高，认为其来源于组织损伤和炎症过程;然而，这种增加的幅度，绝对浓度以及与不良结局的相关性在不同研究中差异很大。对健康个体的无细胞mtDNA的测量表明，大多数“无细胞”mtDNA（>95%）可以从血浆中离心/过滤出0.45至5 μm的尺寸范围，这表明血浆中存在较大形式的含mtDNA复合物，可以被认为是无细胞的。这是否适用于创伤患者（和其他相关疾病状态）以及较大形式的mtDNA的临床相关性尚不清楚。来自健康个体的这些发现还表明，用于产生无细胞血浆的离心速度（在研究中很少一致）可能导致无细胞mtDNA的混合群体，这可能混淆与结果的关联。我们在25名严重创伤患者的这项研究中证明，创伤患者血浆中的大部分游离mtDNA（>95%）在16，000 g离心后被去除。尽管线粒体DNA的较大形式占主导地位，但它们与结果或预期参数（如损伤/休克严重程度，多器官衰竭和炎症标志物）无关，而低分子量无细胞线粒体DNA与这些变量密切相关。
Mitochondrial DNA (mtDNA) acts as a proinflammatory damage-associated molecular pattern that stimulates innate immune activation via Toll-like receptor 9, similarly to bacterial DNA. A number of clinical studies have measured elevated cell-free mtDNA in the plasma of trauma patients, thought to originate from tissue injury and inflammatory processes; however, the magnitude of this increase, the absolute concentration, and the association with poor outcomes varies considerably across studies. Measurements of cell-free mtDNA in healthy individuals have shown that the majority of “cell-free” mtDNA (>95%) can be centrifuged/filtered from plasma in the size range of 0.45 to 5 μm, suggesting that there are larger forms of mtDNA-containing complexes in the plasma that could be considered cell-free. Whether this is true for trauma patients (and other relevant disease states) and the clinical relevance of the larger forms of mtDNA is unknown. These findings from healthy individuals also suggest that the centrifugation speeds used to generate cell-free plasma (which are rarely consistent among studies) could result in mixed populations of cell-free mtDNA that could confound associations with outcomes. We demonstrate in this study of 25 major trauma patients that the majority of the cell-free mtDNA in trauma patient plasma (>95%) is removed after centrifugation at 16,000g. Despite the larger forms of mtDNA being predominant, they do not correlate with outcomes or expected parameters such as injury/shock severity, multiple organ failure, and markers of inflammation, whereas low-molecular-weight cell-free mtDNA correlates strongly with these variables.