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

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?

SUBMITTER: Leijte GP

PROVIDER: S-EPMC7082984 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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

Leijte Guus P GP Rimmelé Thomas T Kox Matthijs M Bruse Niklas N Monard Céline C Gossez Morgane M Monneret Guillaume G Pickkers Peter P Venet Fabienne F

Critical care (London, England) 20200320 1

<h4>Background</h4>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.<h4>Methods</h4>We evaluated mHLA-DR expression kinetics in 241 septic shock patients with different primary sites of infection and pathogens. Furthermore, we used unsupervised clusterin ...[more]

PMID: 32192532

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Project description:Background: Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. To date, no biomarker has shown sufficient evidence and ease of application in clinical routine to monitor the complexity of the sepsis-related immune alterations. Multiple levels of interaction of human endogenous retroviruses (HERVs) with the immune response led us to hypothesize that they may be relevant candidates both to contribute to the physiopathology of sepsis and to be part of a molecular signature. In this study, we used a recently described high-density microarray which allows exploring HERVs/MaLRs transcriptome in septic shock patients. Results: About 6.9% of the HERVs/MalRs repertoire is transcribed in whole blood. Concerning the functionality of LTRs, the majority of LTRs are silent (62.9%), 7.5% of LTRs present a putative constitutive promoter or polyA functions, while 20.4% of them may shift from silent to active. Evidence was given that a subset of HERVs/MaLRs and genes were modulated in septic shock patients according to the monocyte HLA-DR (mHLA-DR) expression level measured by flow cytometry, as a proxy of immunosuppression. We then identified a large signature consisting of 193 differentially expressed HERVs/MaLRs probesets further reduced to a smaller 10 HERVs/MaLRs signature. Both signatures, validated in an independent septic shock cohort, identified two groups of patients with different severity features including clinical criteria and the CD74 and CX3CR1 sepsis severity molecular markers. Conclusion: This microarray-based approach unveiled the expression of about 87,912 distinct HERV probesets and identified 764 putative promoter LTRs and 642 putative polyA LTRs in whole blood. HERV/MaLR expression was shown to be tightly modulated in septic shock patients according to mHLA-DR expression. We identified a set of potential molecular biomarkers in septic shock patients partially overlapping immunosuppression (mHLA-DR), and the risk of Health Care associated Infections (HAI) (CD74 ratio), complementary to existing molecular markers of a sepsis patients stratification. We identified a HERV/MaLR signature discriminating patients based on their immunosuppression state and severity.

Dataset Information

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

Publications

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

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