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Intensive Care Medicine
Published in: Intensive Care Medicine 5/2018

Open Access 01-05-2018 | Original

Cell-surface signatures of immune dysfunction risk-stratify critically ill patients: INFECT study

Authors: Andrew Conway Morris, Deepankar Datta, Manu Shankar-Hari, Jacqueline Stephen, Christopher J. Weir, Jillian Rennie, Jean Antonelli, Anthony Bateman, Noel Warner, Kevin Judge, Jim Keenan, Alice Wang, Tony Burpee, K. Alun Brown, Sion M. Lewis, Tracey Mare, Alistair I. Roy, Gillian Hulme, Ian Dimmick, Adriano G. Rossi, A. John Simpson, Timothy S. Walsh

Published in: Intensive Care Medicine | Issue 5/2018

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Abstract

Purpose

Cellular immune dysfunctions, which are common in intensive care patients, predict a number of significant complications. In order to effectively target treatments, clinically applicable measures need to be developed to detect dysfunction. The objective was to confirm the ability of cellular markers associated with immune dysfunction to stratify risk of secondary infection in critically ill patients.

Methods

Multi-centre, prospective observational cohort study of critically ill patients in four UK intensive care units. Serial blood samples were taken, and three cell surface markers associated with immune cell dysfunction [neutrophil CD88, monocyte human leucocyte antigen-DR (HLA-DR) and percentage of regulatory T cells (Tregs)] were assayed on-site using standardized flow cytometric measures. Patients were followed up for the development of secondary infections.

Results

A total of 148 patients were recruited, with data available from 138. Reduced neutrophil CD88, reduced monocyte HLA-DR and elevated proportions of Tregs were all associated with subsequent development of infection with odds ratios (95% CI) of 2.18 (1.00–4.74), 3.44 (1.58–7.47) and 2.41 (1.14–5.11), respectively. Burden of immune dysfunction predicted a progressive increase in risk of infection, from 14% for patients with no dysfunction to 59% for patients with dysfunction of all three markers. The tests failed to risk stratify patients shortly after ICU admission but were effective between days 3 and 9.

Conclusions

This study confirms our previous findings that three cell surface markers can predict risk of subsequent secondary infection, demonstrates the feasibility of standardized multisite flow cytometry and presents a tool which can be used to target future immunomodulatory therapies.

Trial registration

The study was registered with clinicaltrials.gov (NCT02186522).
Appendix
Available only for authorised users
Literature
1.
Gouel-Chéron A, Allaouchiche B, Floccard B, Rimmelé T, Monneret G (2015) Early daily mHLA-DR monitoring predicts forthcoming sepsis in severe trauma patients. Intensive Care Med 41:2229–2230CrossRefPubMed
2.
Allen ML, Peters MJ, Goldman A et al (2002) Early postoperative monocyte deactivation predicts systemic inflammation and prolonged stay in pediatric cardiac intensive care. Crit Care Med 30:1140–1145CrossRefPubMed
3.
Conway Morris A, Anderson N, Brittan M et al (2013) Combined dysfunctions of immune cells predict nosocomial infection in critically ill patients. Brit J Anaes 11:778–787CrossRef
4.
5.
Lee WL, Downey GP (2001) Leukocyte elastase: physiological functions and role in acute lung injury. Am J Respir Crit Care Med 164:896–904CrossRefPubMed
6.
Pène F, Pickkers P, Hotchkiss RS (2016) Is this critically ill patient immunocompromised? Intensive Care Med 42:1051–1054CrossRefPubMed
7.
Vanzant EL, Lopez CM, Ozrazgat-Baslanti T et al (2014) Persistent inflammation, immunosuppression, and catabolism syndrome after severe blunt trauma. J Trauma Acute Care Surg 76:21–30CrossRefPubMedPubMedCentral
8.
Vincent J-L, Rello J, Marshall J et al (2009) International study of the prevalence and outcomes of infection in intensive care units. JAMA 302:2323–2329CrossRefPubMed
9.
Kett DH, Cano E, Quartin AA et al (2011) Implementation of guidelines for management of possible multidrug-resistant pneumonia in intensive care: an observational, multicentre cohort study. Lancet Infect Dis 11:181–189CrossRefPubMed
10.
Morris AC, Brittan M, Wilkinson TS et al (2011) C5a-mediated neutrophil dysfunction is RhoA-dependent and predicts infection in critically ill patients. Blood 117:5178–5188CrossRefPubMed
11.
Conway Morris A, Kefala K, Wilkinson TS et al (2009) C5a mediates peripheral blood neutrophil dysfunction in critically ill patients. Am J Respir Crit Care Med 180:19–28CrossRefPubMed
12.
Döcke WD, Randow F, Syrbe U et al (1997) Monocyte deactivation in septic patients: restoration by IFN-gamma treatment. Nat Med 3:678–681CrossRefPubMed
13.
Lukaszewicz A-C, Grienay M, Resche-Rigon M et al (2009) Monocytic HLA-DR expression in intensive care patients: interest for prognosis and secondary infection prediction. Crit Care Med 37:2746–2752PubMed
14.
Venet F, Chung C-S, Kherouf H et al (2009) Increased circulating regulatory T cells (CD4+CD25+CD127−) contribute to lymphocyte anergy in septic shock patients. Intensive Care Med 35:678–686CrossRefPubMed
15.
Leentjens J, Kox M, van der Hoeven JG, Netea MG, Pickkers P (2013) immunotherapy for the adjunctive treatment of sepsis: from immunosuppression to immunostimulation. Time for a paradigm change? Am J Respir Crit Care Med 187:1287–1293CrossRefPubMed
16.
Conway Morris A, Datta D, Shankar-Hari M, et al (2018) Predicting secondary infections using cell-surface markers of immune cell dysfunction: the INFECT study. J Intensive Care Soc (in press)
17.
Conway Morris A, Datta D, Shankar-Hari M et al (2016) Predictive value of cell-surface markers in infections in critically ill patients: protocol for an observational study (ImmuNe FailurE in Critical Therapy (INFECT) study). BMJ Open 6:e011326CrossRefPubMedPubMedCentral
18.
Suetens C, Morales I, Savey A et al (2007) European surveillance of ICU-acquired infections (HELICS-ICU): methods and main results. J Hosp Infect 65(Suppl 2):171–173CrossRefPubMed
19.
Drewry AM, Ablordeppey EA, Murray ET et al (2016) Comparison of monocyte human leukocyte antigen-DR expression and stimulated tumor necrosis factor alpha production as outcome predictors in severe sepsis: a prospective observational study. Crit Care 20:334CrossRefPubMedPubMedCentral
20.
Seddiki N, Santner-Nanan B, Martinson J et al (2006) Expression of interleukin (IL)-2 and IL-7 receptors discriminates between human regulatory and activated T cells. J Exp Med 203:1693–1700CrossRefPubMedPubMedCentral
21.
Adrie C, Lugosi M, Sonneville R et al (2017) Persistent lymphopenia is a risk factor for ICU-acquired infections and for death in ICU patients with sustained hypotension at admission. Ann Intensive Care 7:30CrossRefPubMedPubMedCentral
22.
Salciccioli JD, Marshall DC, Pimentel MAF et al (2015) The association between the neutrophil-to-lymphocyte ratio and mortality in critical illness: an observational cohort study. Crit Care 19:13CrossRefPubMedPubMedCentral
23.
24.
van Vught LA, Klein Klouwenberg PMC, Spitoni C et al (2016) Incidence, risk factors, and attributable mortality of secondary infections in the intensive care unit after admission for sepsis. JAMA 315:1469–1479CrossRefPubMed
25.
Unnewehr H, Rittirsch D, Sarma JV et al (2013) Changes and regulation of the C5a receptor on neutrophils during septic shock in humans. J Immunol 190:4215–4225CrossRefPubMed
26.
Huang L-F, Yao Y-M, Dong N, Yu Y, He L-X, Sheng Z-Y (2010) Association between regulatory T cell activity and sepsis and outcome of severely burned patients: a prospective, observational study. Crit Care 14:R3CrossRefPubMedPubMedCentral
27.
Cheadle WG, Hershman MJ, Wellhausen SR, Polk HC (1991) HLA-DR antigen expression on peripheral blood monocytes correlates with surgical infection. Am J Surg 161:639–645CrossRefPubMed
28.
Meisel C, Schefold JC, Pschowski R et al (2009) Granulocyte-macrophage colony-stimulating factor to reverse sepsis-associated Immunosuppression: a double-blind, randomized, placebo-controlled multicenter trial. Am J Respir Crit Care Med 180:640–648CrossRefPubMed
29.
Singanayagam A, Schembri S, Chalmers JD (2013) Predictors of mortality in hospitalized adults with acute exacerbation of chronic obstructive pulmonary disease. A systematic review and meta-analysis. Ann ATS 10:81–89CrossRef
30.
Sabatine MS, Antman EM (2003) The thrombolysis in myocardial infarction risk score in unstable angina/non-ST-segment elevation myocardial infarction. J Am Coll Cardiol 41:S89–S95CrossRef
Metadata
Title
Cell-surface signatures of immune dysfunction risk-stratify critically ill patients: INFECT study
Authors
Andrew Conway Morris
Deepankar Datta
Manu Shankar-Hari
Jacqueline Stephen
Christopher J. Weir
Jillian Rennie
Jean Antonelli
Anthony Bateman
Noel Warner
Kevin Judge
Jim Keenan
Alice Wang
Tony Burpee
K. Alun Brown
Sion M. Lewis
Tracey Mare
Alistair I. Roy
Gillian Hulme
Ian Dimmick
Adriano G. Rossi
A. John Simpson
Timothy S. Walsh
Publication date
01-05-2018
Publisher
Springer Berlin Heidelberg
Published in
Intensive Care Medicine / Issue 5/2018
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-018-5247-0

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