A Transcriptomic Biomarker to Quantify Systemic Inflammation in Sepsis - A Prospective Multicenter Phase II Diagnostic Study

被引：45

作者：

Bauer, Michael ^{[1
,2
]}

Giamarellos-Bourboulis, Evangelos J. ^{[2
,3
]}

Kortgen, Andreas ^{[1
,2
]}

Moeller, Eva ^{[4
]}

Felsmann, Karen ^{[4
]}

Cavaillon, Jean Marc ^{[5
]}

Guntinas-Lichius, Orlando ^{[6
,7
]}

Rutschmann, Olivier ^{[8
,9
]}

Ruryk, Andriy ^{[2
]}

Kohl, Matthias ^{[10
]}

Wlotzka, Britta ^{[11
]}

Russwurm, Stefan ^{[1
]}

Marshall, John C. ^{[12
]}

Reinhart, Konrad ^{[1
,2
]}

机构：

[1] Jena Univ Hosp, Dept Anesthesiol & Intens Care Med, Erlanger Allee 101, D-07646 Jena, Germany

[2] Jena Univ Hosp, Ctr Sepsis Control & Care, Erlanger Allee 101, D-07646 Jena, Germany

[3] Univ Athens, Sch Med, Dept Internal Med 4, 1 Rimini Str, Athens 12462, Greece

[4] Analyt Jena AG Germany, Sepsis Diagnost Expert Grp, Konrad Zuse Str 1, D-07745 Jena, Germany

[5] Inst Pasteur, Unit Cytokines & Inflammat, F-75015 Paris, France

[6] Jena Univ Hosp, Dept Otolaryngol, Lessingstr 2, D-07740 Jena, Germany

[7] Jena Univ Hosp, Inst Phoniatry & Pedaudiol, Lessingstr 2, D-07740 Jena, Germany

[8] Univ Hosp Geneva, Dept Commun Primary Care & Emergency Med, Div Emergency Med, 2 Rue Gabrielle Perret Gentil, CH-1211 Geneva 14, Switzerland

[9] Fac Med, 2 Rue Gabrielle Perret Gentil, CH-1211 Geneva 14, Switzerland

[10] Furtwangen Univ, Fac Med & Life Sci, Jakob Kienzle Str 17, D-78054 Villingen Schwenningen, Germany

[11] State Dev Corp Thuringia, Mainzerhofstr 12, D-99084 Erfurt, Germany

[12] Univ Toronto, St Michaels Hosp, 30 Bond St,Bond 4-014, Toronto, ON M5B 1W8, Canada

来源：

EBIOMEDICINE | 2016年 / 6卷

关键词：

Host response; Transcriptomic profiling; Adaptive immunity; Point-of-care; RT-qPCR; Clinical utility; RESPONSE SYNDROME; EXPRESSION; GENES; CARE; INFECTIONS;

D O I：

10.1016/j.ebiom.2016.03.006

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Development of a dysregulated immune response discriminates sepsis from uncomplicated infection. Currently used biomarkers fail to describe simultaneously occurring pro-and anti-inflammatory responses potentially amenable to therapy. Marker candidates were screened by microarray and, after transfer to a platform allowing point-of-care testing, validated in a confirmation set of 246 medical and surgical patients. We identified up-regulated pathways reflecting innate effector mechanisms, while down-regulated pathways related to adaptive lymphocyte functions. A panel of markers composed of three up-(Toll-like receptor 5; Protectin; Clusterin) and 4 down-regulated transcripts (Fibrinogen-like 2; Interleukin-7 receptor; Major histocompatibility complex class II, DP alpha1; Carboxypeptidase, vitellogenic-like) described the magnitude of immune alterations. The created gene expression score was significantly greater in patients with definite as well as with possible/probable infection than with no infection (median (Q25/Q75): 80 (60/101)) and 81 (58/97 vs. 49 (27/66), AUC-ROC = 0.812 (95%-CI 0.755-0.869), p < 0.0001). Down-regulated lymphocyte markers were associated with prognosis with good sensitivity but limited specificity. Quantifying systemic inflammation by assessment of both pro-and anti-inflammatory innate and adaptive immune responses provides a novel option to identify patients-at-risk and may facilitate immune interventions in sepsis. (C) 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

引用

页码：114 / 125

页数：12

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