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Sci Transl Med. 2014 Sep 24;6(255):255ra131. doi: 10.1126/scitranslmed.3009701.

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

Author information

1
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.
2
Baxter Laboratory in Stem Cell Biology, Stanford University, Stanford, CA 94305, USA. Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA.
3
Baxter Laboratory in Stem Cell Biology, Stanford University, Stanford, CA 94305, USA. Biomedical Informatics Program, Stanford University, Stanford, CA 94305, USA.
4
Baxter Laboratory in Stem Cell Biology, Stanford University, Stanford, CA 94305, USA. Department of Mathematics, Stanford University, Stanford, CA 94305, USA. Center for Cancer Systems Biology, Stanford University, Stanford, CA 94305, USA.
5
Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
6
Department of Orthopedic Surgery, Stanford University, Redwood City, CA 94063, USA.
7
Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA.
8
Baxter Laboratory in Stem Cell Biology, Stanford University, Stanford, CA 94305, USA. Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA. Department of Obstetrics and Gynecology, Stanford University, Stanford, CA 94305, USA.
9
Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA. ang@stanford.edu gnolan@stanford.edu.
10
Baxter Laboratory in Stem Cell Biology, Stanford University, Stanford, CA 94305, USA. Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA. ang@stanford.edu gnolan@stanford.edu.

Abstract

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01578798.

PMID:
25253674
PMCID:
PMC4334126
DOI:
10.1126/scitranslmed.3009701
[Indexed for MEDLINE]
Free PMC Article

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