Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Critical Care
Published in: Critical Care 1/2020

01-12-2020 | Septicemia | Research

Monocytic HLA-DR expression kinetics in septic shock patients with different pathogens, sites of infection and adverse outcomes

Authors: Guus P. Leijte, Thomas Rimmelé, Matthijs Kox, Niklas Bruse, Céline Monard, Morgane Gossez, Guillaume Monneret, Peter Pickkers, Fabienne Venet

Published in: Critical Care | Issue 1/2020

Login to get access

Abstract

Background

Decreased monocytic (m)HLA-DR expression is the most studied biomarker of sepsis-induced immunosuppression. To date, little is known about the relationship between sepsis characteristics, such as the site of infection, causative pathogen, or severity of disease, and mHLA-DR expression kinetics.

Methods

We evaluated mHLA-DR expression kinetics in 241 septic shock patients with different primary sites of infection and pathogens. Furthermore, we used unsupervised clustering analysis to identify mHLA-DR trajectories and evaluated their association with outcome parameters.

Results

No differences in mHLA-DR expression kinetics were found between groups of patients with different sites of infection (abdominal vs. respiratory, p = 0.13; abdominal vs. urinary tract, p = 0.53) and between pathogen categories (Gram-positive vs. Gram-negative, p = 0.54; Gram-positive vs. negative cultures, p = 0.84). The mHLA-DR expression kinetics differed between survivors and non-survivors (p < 0.001), with an increase over time in survivors only. Furthermore, we identified three mHLA-DR trajectories (‘early improvers’, ‘delayed or non-improvers’ and ‘decliners’). The probability for adverse outcome (secondary infection or death) was higher in the delayed or non-improvers and decliners vs. the early improvers (delayed or non-improvers log-rank p = 0.03, adjusted hazard ratio 2.0 [95% CI 1.0–4.0], p = 0.057 and decliners log-rank p = 0.01, adjusted hazard ratio 2.8 [95% CI 1.1–7.1], p = 0.03).

Conclusion

Sites of primary infection or causative pathogens are not associated with mHLA-DR expression kinetics in septic shock patients. However, patients showing delayed or no improvement in or a declining mHLA-DR expression have a higher risk for adverse outcome compared with patients exhibiting a swift increase in mHLA-DR expression. Our study signifies that changes in mHLA-DR expression over time, and not absolute values or static measurements, are of clinical importance in septic shock patients.
Appendix
Available only for authorised users
Literature
1.
Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). Jama. 2016;315(8):801–10.CrossRef
2.
Bruse N, Leijte GP, Pickkers P, Kox M. New frontiers in precision medicine for sepsis-induced immunoparalysis. Expert Rev Clin Immunol. 2019;15(3):251–63.CrossRef
3.
Venet F, Lukaszewicz AC, Payen D, Hotchkiss R, Monneret G. Monitoring the immune response in sepsis: a rational approach to administration of immunoadjuvant therapies. Curr Opin Immunol. 2013;25(4):477–83.CrossRef
4.
van der Poll T, van de Veerdonk FL, Scicluna BP, Netea MG. The immunopathology of sepsis and potential therapeutic targets. Nat Rev Immunol. 2017;17(7):407–20.CrossRef
5.
Venet F, Monneret G. Advances in the understanding and treatment of sepsis-induced immunosuppression. Nat Rev Nephrol. 2017;14:121.CrossRef
6.
Landelle C, Lepape A, Voirin N, Tognet E, Venet F, Bohe J, et al. Low monocyte human leukocyte antigen-DR is independently associated with nosocomial infections after septic shock. Intensive Care Med. 2010;36(11):1859–66.CrossRef
7.
Monneret G, Lepape A, Voirin N, Bohe J, Venet F, Debard AL, et al. Persisting low monocyte human leukocyte antigen-DR expression predicts mortality in septic shock. Intensive Care Med. 2006;32(8):1175–83.CrossRef
8.
Gouel-Cheron A, Allaouchiche B, Floccard B, Rimmele T, Monneret G. Early daily mHLA-DR monitoring predicts forthcoming sepsis in severe trauma patients. Intensive Care Med. 2015;41(12):2229–30.CrossRef
9.
Lukaszewicz AC, Grienay M, Resche-Rigon M, Pirracchio R, Faivre V, Boval B, et al. Monocytic HLA-DR expression in intensive care patients: interest for prognosis and secondary infection prediction. Crit Care Med. 2009;37(10):2746–52.PubMed
10.
Wu JF, Ma J, Chen J, Ou-Yang B, Chen MY, Li LF, et al. Changes of monocyte human leukocyte antigen-DR expression as a reliable predictor of mortality in severe sepsis. Critical Care (London, England). 2011;15(5):R220.CrossRef
11.
Cajander S, Rasmussen G, Tina E, Magnuson A, Soderquist B, Kallman J, et al. Dynamics of monocytic HLA-DR expression differs between bacterial etiologies during the course of bloodstream infection. PLoS One. 2018;13(2):e0192883.CrossRef
12.
Janols H, Wullt M, Bergenfelz C, Björnsson S, Lickei H, Janciauskiene S, et al. Heterogeneity among septic shock patients in a set of immunoregulatory markers. Eur J Clin Microbiol Infect Dis. 2014;33(3):313–24.CrossRef
13.
Nielsen JD, Rosenthal JS, Sun Y, Day DM, Bevc I, Duchesne T. Group-based criminal trajectory analysis using cross-validation criteria. Communications Statistics - Theory Methods. 2014;43(20):4337–56.CrossRef
14.
van Vught LA, Klein Klouwenberg PM, Spitoni C, Scicluna BP, Wiewel MA, Horn J, et al. Incidence, risk factors, and attributable mortality of secondary infections in the intensive care unit after admission for Sepsis. Jama. 2016;315(14):1469–79.CrossRef
15.
Yu SL, Chen HW, Yang PC, Peck K, Tsai MH, Chen JJ, et al. Differential gene expression in gram-negative and gram-positive sepsis. Am J Respir Crit Care Med. 2004;169(10):1135–43.CrossRef
16.
Drewry AM, Ablordeppey EA, Murray ET, Beiter ER, Walton AH, Hall MW, et al. 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. Critical Care (London, England). 2016;20(1):334.CrossRef
17.
Pfortmueller CA, Meisel C, Fux M, Schefold JC. Assessment of immune organ dysfunction in critical illness: utility of innate immune response markers. Intensive Care Med Exper. 2017;5(1):49.CrossRef
18.
Dimitrov E, Enchev E, Minkov G, Halacheva K, Yovtchev Y. Poor Outcome Could Be Predicted by Lower Monocyte Human Leukocyte Antigen-DR Expression in Patients with Complicated Intra-Abdominal Infections: A Review. Surg Infect. 2020;21(2):77–80.CrossRef
19.
Cheron A, Floccard B, Allaouchiche B, Guignant C, Poitevin F, Malcus C, et al. Lack of recovery in monocyte human leukocyte antigen-DR expression is independently associated with the development of sepsis after major trauma. Critical care (London, England). 2010;14(6):R208.CrossRef
20.
Conway Morris A, Anderson N, Brittan M, Wilkinson TS, McAuley DF, Antonelli J, et al. Combined dysfunctions of immune cells predict nosocomial infection in critically ill patients. Br J Anaesth. 2013;111(5):778–87.CrossRef
21.
Conway Morris A, Datta D, Shankar-Hari M, Stephen J, Weir CJ, Rennie J, et al. Cell-surface signatures of immune dysfunction risk-stratify critically ill patients: INFECT study. Intensive Care Med. 2018;44(5):627–35.CrossRef
22.
Meisel C, Schefold JC, Pschowski R, Baumann T, Hetzger K, Gregor J, et al. Granulocyte-macrophage colony-stimulating factor to reverse sepsis-associated immunosuppression: a double-blind, randomized, placebo-controlled multicenter trial. Am J Respir Crit Care Med. 2009;180(7):640–8.CrossRef
23.
Hotchkiss RS, Colston E, Yende S, Crouser ED, Martin GS, Albertson T, et al. Immune checkpoint inhibition in sepsis: a phase 1b randomized study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of nivolumab. Intensive Care Med. 2019;45(10):1360–71.CrossRef
24.
Hotchkiss RS, Colston E, Yende S, Angus DC, Moldawer LL, Crouser ED, et al. Immune checkpoint inhibition in sepsis: a phase 1b randomized, placebo-controlled, single ascending dose study of antiprogrammed cell death-ligand 1 antibody (BMS-936559). Crit Care Med. 2019;47(5):632–42.CrossRef
25.
Pickkers P, van der Poll T. What's new in immunostimulating strategies in the ICU. Intensive Care Med. 2019;45(1):110–2.CrossRef
26.
Stanski NL, Wong HR. Prognostic and predictive enrichment in sepsis. Nat Rev Nephrol. 2020;16(1):20–31.CrossRef
27.
Hotchkiss RS, Monneret G, Payen D. Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy. Nat Rev Immunol. 2013;13(12):862–74.CrossRef
28.
Leijte GP, Custers H, Gerretsen J, Heijne A, Roth J, Vogl T, et al. Increased plasma levels of danger-associated molecular patterns are associated with immune suppression and postoperative infections in patients undergoing cytoreductive surgery and Hyperthermic Intraperitoneal chemotherapy. Front Immunol. 2018;9:663.CrossRef
Metadata
Title
Monocytic HLA-DR expression kinetics in septic shock patients with different pathogens, sites of infection and adverse outcomes
Authors
Guus P. Leijte
Thomas Rimmelé
Matthijs Kox
Niklas Bruse
Céline Monard
Morgane Gossez
Guillaume Monneret
Peter Pickkers
Fabienne Venet
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2020
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-020-2830-x

Other articles of this Issue 1/2020

Critical Care 1/2020 Go to the issue

Letter

Universal mobile protection system for aerosol-generating medical interventions in COVID-19 patients

Research

Severe manifestations of SARS-CoV-2 in children and adolescents: from COVID-19 pneumonia to multisystem inflammatory syndrome: a multicentre study in pediatric intensive care units in Spain

Research

Prediction of the development of acute kidney injury following cardiac surgery by machine learning

Research Letter

Persistent hypermetabolism and longitudinal energy expenditure in critically ill patients with COVID-19

Research Letter

Evaluation of the E-PRE-DELIRIC prediction model for ICU delirium: a retrospective validation in a UK general ICU

Letter

A new clinical trial to test high-dose vitamin C in patients with COVID-19