Is this critically ill patient immunocompromised?

Pène, Frédéric; Pickkers, Peter; Hotchkiss, Richard S.

doi:10.1007/s00134-015-4161-y

Cited by 31 publications

(28 citation statements)

References 19 publications

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“…Sepsis is a leading cause of death worldwide. It often manifests as a complex immune dysfunction where a hyper-inflammatory reaction, the "cytokine storm", simultaneously occurs alongside an 2 of 22 insufficient ("hypo") immune reaction [1,2]. Several studies have demonstrated that persistent immunosuppression is associated with a poor patient outcome [3,4].…”

Section: Introductionmentioning

confidence: 99%

Differential Gene Expression in Circulating CD14+ Monocytes Indicates the Prognosis of Critically Ill Patients with Sepsis

Liepelt

Hohlstein

Gussen

et al. 2020

JCM

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Critical illness and sepsis are characterized by drastic changes in the systemic innate immune response, particularly involving monocytes. The exact monocyte activation profile during sepsis, however, has remained obscure. Therefore, we prospectively analyzed the gene expression profile of circulating CD14+ monocytes from healthy volunteers (n = 54) and intensive care unit (ICU) patients (n = 76), of which n = 36 had sepsis. RNA sequencing of selected samples revealed that monocytes from septic ICU patients display a peculiar activation pattern, which resembles characteristic functional stages of monocyte-derived macrophages and is distinct from controls or non-sepsis ICU patients. Focusing on 55 highly variable genes selected for further investigation, arachidonate 5-lipoxygenase-activating protein (ALOX5AP) was highly upregulated in monocytes of ICU patients and only normalized during 7 days in the ICU in non-sepsis patients. Strikingly, low monocytic guanine nucleotide exchange factor 10-like protein (ARHGEF10L) mRNA expression was associated with the disease severity and mortality of ICU patients. Collectively, our comprehensive analysis of circulating monocytes in critically ill patients revealed a distinct activation pattern, particularly in ICU patients with sepsis. The association with disease severity, the longitudinal recovery or lack thereof during the ICU stay, and the association with prognosis indicate the clinical relevance of monocytic gene expression profiles during sepsis.

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Section: Introductionmentioning

confidence: 99%

Differential Gene Expression in Circulating CD14+ Monocytes Indicates the Prognosis of Critically Ill Patients with Sepsis

Liepelt

Hohlstein

Gussen

et al. 2020

JCM

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“…A hallmark of critical illness is systemic inflammation and immune-mediated organ damage [5]. However it is increasingly clear that this immune activation is accompanied by an equally pronounced immunodepression [6], and that a persistence of this immune duality is associated with a complicated intensive care unit (ICU) course [7]. If effective treatments for this complex state of immune dysfunction are to be developed, we need to identify clinical and laboratory markers for it.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2018

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PurposeCellular 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.MethodsMulti-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.ResultsA 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.ConclusionsThis 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 registrationThe study was registered with clinicaltrials.gov (NCT02186522).Electronic supplementary materialThe online version of this article (10.1007/s00134-018-5247-0) contains supplementary material, which is available to authorized users.

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“…The recognition of sepsis-induced immunoparalysis is not straightforward because the clinical manifestations associated with the switch from the hyperinflammatory state to CARS and the full-blown depression of the immune capabilities are not so protean as the symptoms of SS [18]. Moreover, the SSC guidelines focus almost exclusively on the former and pay much less attention, if any, to the latter.…”

Section: The Diagnosis Of Immunoparalysismentioning

confidence: 99%

Immunoparalysis in Septic Shock Patients

Berlot¹,

Passero²

2020

Infectious Process and Sepsis

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In the recent years, it has become clear that septic shock is characterized by the simultaneous production of inflammatory and anti-inflammatory mediators; the primary role of the latter is to counterbalance the former, thus limiting the severity of their systemic effects. However, in a number of patients, the anti-inflammatory substances can cause a downregulation in both the innate and adaptive immune capabilities, leading a second phase characterized to secondary infections caused by opportunist germs and the reactivation of latent viruses, muscle wasting; altogether, these abnormalities set the stage for a chronic critical condition. This condition, whose identification is relatively recent, is called immunoparalysis. Unfortunately, the current approach to septic shock is focused much more on the inflammatory phase than in the ensuing immunoparalysis, whose diagnosis can be challenging. In this chapter, the role played by both classes of mediators, the monitoring of the immune system, and the possible current and not yet available therapeutic strategies of immunoparalysis are reviewed and discussed.

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Is this critically ill patient immunocompromised?

Cited by 31 publications

References 19 publications

Differential Gene Expression in Circulating CD14+ Monocytes Indicates the Prognosis of Critically Ill Patients with Sepsis

Differential Gene Expression in Circulating CD14+ Monocytes Indicates the Prognosis of Critically Ill Patients with Sepsis

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

Immunoparalysis in Septic Shock Patients

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