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Monocyte Trajectories Endotypes Are Associated With Worsening in Septic Patients.

ABSTRACT: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. The immune system plays a key role in sepsis onset and remains dysregulated over time in a heterogeneous manner. Here, we decipher the heterogeneity of the first week evolution of the monocyte HLA-DR (mHLA-DR) surface protein expression in septic patients, a key molecule for adaptive immunity onset. We found and verified four distinctive trajectories endotypes in a discovery (n = 276) and a verification cohort (n = 102). We highlight that 59% of septic patients exhibit low or decreasing mHLA-DR expression while in others mHLA-DR expression increased. This study depicts the first week behavior of mHLA-DR over time after sepsis onset and shows that initial and third day mHLA-DR expression measurements is sufficient for an early risk stratification of sepsis patients. These patients might benefit from immunomodulatory treatment to improve outcomes. Going further, our study introduces a way of deciphering heterogeneity of immune system after sepsis onset which is a first step to reach a more comprehensive landscape of sepsis.

SUBMITTER: Bodinier M

PROVIDER: S-EPMC8667763 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Monocyte Trajectories Endotypes Are Associated With Worsening in Septic Patients.

Bodinier Maxime M Peronnet Estelle E Brengel-Pesce Karen K Conti Filippo F Rimmelé Thomas T Textoris Julien J Vedrine Christophe C Quemeneur Laurence L Griffiths Andrew D AD Tan Lionel K LK Venet Fabienne F Maucort-Boulch Delphine D Monneret Guillaume G

Frontiers in immunology 20211129

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. The immune system plays a key role in sepsis onset and remains dysregulated over time in a heterogeneous manner. Here, we decipher the heterogeneity of the first week evolution of the monocyte HLA-DR (mHLA-DR) surface protein expression in septic patients, a key molecule for adaptive immunity onset. We found and verified four distinctive trajectories endotypes in a discovery (n = 276) and a verifi ...[more]

PMID: 34912347

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Project description:BackgroundSepsis causes a high rate of mortality and long-term morbidity, associated with an imbalance of innate immunity against infections and inflammation. Obesity and diabetes increase the risk for disease severity. Monocyte dysfunction plays a major role and justify further investigations.ObjectiveTo investigate the distribution and inflammatory phenotypes in circulating monocyte subsets in patients manifesting with sepsis including septic shock with and without obesity and diabetes.MethodsA total of 235 blood samples were tested from critically ill adult patients registered at the intensive care unit (ICU). The cohorts were divided into non-diabetic groups with or without obesity and diabetic groups with or without obesity, suffering from sepsis or septic shock. We determined frequencies of total monocytes and of monocyte subsets in the circulation and density expression levels of functional markers, including CD14, CD16, HLA-DR, CD33, CD163, CD206, and arginase-1 by flow cytometric analysis.ResultsWhen progressing to septic shock in non-diabetic and diabetic patients, the percentages of total monocytes among the leukocyte population and of CD33+ and CD14+ monocytes among the monocyte population were consistently down-regulated compared to non-sepsis in non-diabetic and diabetic patients, respectively. Non-diabetic sepsis patients further presented with decreased CD33 and up-regulated CD163 expression density, which was absent in diabetic patients. We subsequently addressed obesity-related changes of monocytes in non-diabetic and diabetic septic patients. Obese septic patients with diabetes were unique in displaying increased monocytic CD16 and CD163 expression. However, obese septic patients without diabetes solely presented with lower amounts of non-classical monocytes. Body mass index (BMI) dependent changes were restricted to diabetic septic patients, with a significantly higher diminution of the classical monocyte subset and concomitantly increased CD16 expression densities.ConclusionDistribution and phenotypes of monocyte subsets were differentially modulated in critically ill patients with and without metabolic disease when progressing to sepsis or septic shock. Only diabetic septic patients displayed decline of classical monocytes and increase of CD16 expression densities. Therefore, diabetes but not obesity appears to promote the inflammatory phenotype of circulating monocytes in critically ill patients.

Project description:BackgroundSeptic shock has a high incidence and mortality rate in Intensive Care Units (ICUs). Earlier intravenous fluid resuscitation can significantly improve outcomes in septic patients but easily leads to fluid overload (FO), which is associated with poor clinical outcomes. A single point value of fluid cannot provide enough fluid information. The aim of this study was to investigate the impact of fluid balance (FB) latent trajectories on clinical outcomes in septic patients.MethodsPatients were diagnosed with septic shock during the first 48 h, and sequential fluid data for the first 3 days of ICU admission were included. A group-based trajectory model (GBTM) which is designed to identify groups of individuals following similar developmental trajectories was used to identify latent subgroups of individuals following a similar progression of FB. The primary outcomes were hospital mortality, organ dysfunction, major adverse kidney events (MAKE) and severe respiratory adverse events (SRAE). We used multivariable Cox or logistic regression analysis to assess the association between FB trajectories and clinical outcomes.ResultsNine hundred eighty-six patients met the inclusion criteria and were assigned to GBTM analysis, and three latent FB trajectories were detected. 64 (6.5%), 841 (85.3%), and 81 (8.2%) patients were identified to have decreased, low, and high FB, respectively. Compared with low FB, high FB was associated with increased hospital mortality [hazard ratio (HR) 1.63, 95% confidence interval (CI) 1.22-2.17], organ dysfunction [odds ratio (OR) 2.18, 95% CI 1.22-3.42], MAKE (OR 1.80, 95% CI 1.04-2.63) and SRAE (OR 2.33, 95% CI 1.46-3.71), and decreasing FB was significantly associated with decreased MAKE (OR 0.46, 95% CI 0.29-0.79) after adjustment for potential covariates.ConclusionLatent subgroups of septic patients followed a similar FB progression. These latent fluid trajectories were associated with clinical outcomes. The decreasing FB trajectory was associated with a decreased risk of hospital mortality and MAKE.

Dataset Information

Monocyte Trajectories Endotypes Are Associated With Worsening in Septic Patients.

Publications

Monocyte Trajectories Endotypes Are Associated With Worsening in Septic Patients.

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