Gaudillière Brice, Fragiadakis Gabriela K, Bruggner Robert V, Nicolau Monica, Finck Rachel, Tingle Martha, Silva Julian, Ganio Edward A, Yeh Christine G, Maloney William J, Huddleston James I, Goodman Stuart B, Davis Mark M, Bendall Sean C, Fantl Wendy J, Angst Martin S, Nolan Garry P
Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA. Baxter Laboratory in Stem Cell Biology, Stanford University, Stanford, CA 94305, USA.
Baxter Laboratory in Stem Cell Biology, Stanford University, Stanford, CA 94305, USA. Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA.
Sci Transl Med. 2014 Sep 24;6(255):255ra131. doi: 10.1126/scitranslmed.3009701.
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 phenotypic 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 (signal transducer and activator of transcription), CREB (adenosine 3',5'-monophosphate response element-binding protein), and NF-κB (nuclear factor κB) signaling responses in subsets of CD14(+) monocytes (R = 0.7 to 0.8, false discovery rate <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.
手术恢复延迟会给个人带来痛苦，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情况仍不明确。我们应用单细胞质谱流式细胞术对32例行髋关节置换术患者的系列全血样本进行检测，以全面表征手术创伤后的免疫表型和功能反应。对精确表型的免疫细胞亚群中14,000个磷酸化事件的同步分析揭示了患者之间一致的信号反应，界定了一种手术免疫特征。当与手术恢复的临床参数（包括功能损害和疼痛）进行回归分析时，发现与CD14(+)单核细胞亚群中的STAT3（信号转导和转录激活因子）、CREB（腺苷3',5'-单磷酸反应元件结合蛋白）和NF-κB（核因子κB）信号反应有很强的相关性（R = 0.7至0.8，错误发现率<0.01）。这些初步结果证明了质谱流式细胞术在相关临床背景下检测人体免疫系统的能力。从机制上得出的免疫相关指标指向了诊断特征和潜在的治疗靶点，有望在术后改善患者的恢复情况。
