Clinical recovery from surgery correlates with single-cell immune signatures.

Clinical recovery from surgery correlates with single-cell immune signatures.
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DOI:
10.1126/scitranslmed.3009701
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发表时间:
2014-09-24
影响因子:
17.1
通讯作者:
Nolan GP
Nolan GP
中科院分区:
医学1区
文献类型:
--
作者:
Gaudillière B;Fragiadakis GK;Bruggner RV;Nicolau M;Finck R;Tingle M;Silva J;Ganio EA;Yeh CG;Maloney WJ;Huddleston JI;Goodman SB;Davis MM;Bendall SC;Fantl WJ;Angst MS;Nolan GP

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手术后的延迟恢复会给个人带来痛苦,并造成巨大的社会和经济成本。免疫机制是否决定手术创伤后的恢复仍不明确。应用单细胞细胞计数技术对32例髋关节置换术患者的全血样本进行分析,以全面表征手术创伤后的表型和功能免疫反应。对精确表型免疫细胞亚群中14,000个磷酸化事件的同时分析揭示了患者之间统一的信号反应,划定了手术免疫特征。当与手术恢复的临床参数(包括功能损伤和疼痛)进行回归时,发现CD14+单核细胞亚群中的STAT3、CREB和NF-kB信号反应具有很强的相关性(R= 0.7-0.8, FDR < 0.01)。这些哨兵结果表明,在相关的临床背景下,细胞计数术有能力调查人类免疫系统。机械衍生的免疫相关点指向诊断特征和潜在的治疗靶点,可以改善术后患者的恢复。
Delayed recovery from surgery causes personal suffering and substantial societal and economic costs. Whether immune mechanisms determine recovery after surgical trauma remains ill-defined. Single-cell mass cytometry was applied to serial whole blood samples from 32 patients undergoing hip replacement to comprehensively characterize the phenotypical and functional immune response to surgical trauma. The simultaneous analysis of 14,000 phosphorylation events in precisely phenotyped immune cell subsets revealed uniform signaling responses among patients, demarcating a surgical immune signature. When regressed against clinical parameters of surgical recovery, including functional impairment and pain, strong correlations were found with STAT3, CREB and NF-kB signaling responses in subsets of CD14+ monocytes (R=0.7–0.8, FDR < 0.01). These sentinel results demonstrate the capacity of mass cytometry to survey the human immune system in a relevant clinical context. The mechanistically derived immune correlates point to diagnostic signatures, and potential therapeutic targets, that could postoperatively improve patient recovery.
骨髓来源的巨噬细胞的消耗弥漫于对手术的先天免疫反应并减少术后记忆功能障碍。
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