Remote immune processes revealed by immune-derived circulating cell-free DNA.
Remote immune processes revealed by immune-derived circulating cell-free DNA.
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作者：
Fox-Fisher I;Piyanzin S;Ochana BL;Klochendler A;Magenheim J;Peretz A;Loyfer N;Moss J;Cohen D;Drori Y;Friedman N;Mandelboim M;Rothenberg ME;Caldwell JM;Rochman M;Jamshidi A;Cann G;Lavi D;Kaplan T;Glaser B;Shemer R;Dor Y
血细胞计数通常无法报告远处组织中发生的免疫过程。在这里，我们利用循环游离 DNA (cfDNA) 中免疫细胞类型特异性甲基化模式来研究人类免疫细胞动力学。我们对健康个体 (N = 242) 中特定免疫细胞类型释放的 cfDNA 进行了横截面和纵向特征分析。与血细胞计数相反，免疫 cfDNA 水平没有个体稳态，这表明 cfDNA 浓度反映了细胞存活的调整以维持稳态细胞数量。我们还观察到免疫稳态扰动时免疫源性 cfDNA 选择性升高。接种流感疫苗后 (N = 92)，B 细胞衍生的 cfDNA 水平先于 B 细胞计数升高并预测抗体产生的功效。嗜酸性粒细胞性食管炎 (N = 21) 和 B 细胞淋巴瘤 (N = 27) 患者分别表现出嗜酸性粒细胞和 B 细胞 cfDNA 的选择性升高，而血液中的细胞计数无法检测到这一点。免疫衍生的 cfDNA 提供了一种新的生物标志物，用于监测对生理和病理过程的免疫反应，这是使用传统方法无法实现的。
Blood cell counts often fail to report on immune processes occurring in remote tissues. Here, we use immune cell type-specific methylation patterns in circulating cell-free DNA (cfDNA) for studying human immune cell dynamics. We characterized cfDNA released from specific immune cell types in healthy individuals (N = 242), cross sectionally and longitudinally. Immune cfDNA levels had no individual steady state as opposed to blood cell counts, suggesting that cfDNA concentration reflects adjustment of cell survival to maintain homeostatic cell numbers. We also observed selective elevation of immune-derived cfDNA upon perturbations of immune homeostasis. Following influenza vaccination (N = 92), B-cell-derived cfDNA levels increased prior to elevated B-cell counts and predicted efficacy of antibody production. Patients with eosinophilic esophagitis (N = 21) and B-cell lymphoma (N = 27) showed selective elevation of eosinophil and B-cell cfDNA, respectively, which were undetectable by cell counts in blood. Immune-derived cfDNA provides a novel biomarker for monitoring immune responses to physiological and pathological processes that are not accessible using conventional methods.