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HLA-DR Expression on Monocytes and Sepsis Index Are Useful in Predicting Sepsis.

ABSTRACT: The reduction of mortality in patients with sepsis depends on the early identification and treatment of at-risk patients. The aim was to evaluate the HLA-DR expression on the surface of monocytes (_MHLA-DR ratio), the sepsis index (CD64 expression on neutrophils/_MHLA-DR ratio), and C-reactive protein (CRP) with the development of sepsis. We prospectively enrolled 77 critically ill patients, 59 with stroke and 18 with traumatic brain injuries. The biomarkers were tested at the baseline and 3, 6, 9, 12, and 15 days later. Most patients (71%) developed sepsis (4.2 ± 1.3 days after admission). On day 3, those subsequently developing sepsis had lower levels of _MHLA-DR+ (81.7 ± 16.2% vs. 88.5 ± 12.1%, p < 0.05) and higher sepsis indexes (0.19 ± 0.19 vs. 0.08 ± 0.08, p < 0.01) than those not developing sepsis. The _MHLA-DR ratio slowly recovered before day 6, while the sepsis index remained raised in septic patients up to day 9 (p < 0.05). To predict the development of sepsis, optimal cut-offs were CRP levels > 106.90 mg/mL (74.19% sensitivity, 69.49 specificity) and _MHLA-DR expression rate < 72.80% (45.31% sensitivity, 89.47% specificity). The periodic monitoring of the _MHLA-DR expression together with CRP and sepsis index may help to identify patients in the ICU at increased risk of developing sepsis.

SUBMITTER: Quirant-Sanchez B

PROVIDER: S-EPMC10377223 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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HLA-DR Expression on Monocytes and Sepsis Index Are Useful in Predicting Sepsis.

Quirant-Sánchez Bibiana B Plans-Galván Oriol O Lucas Ester E Argudo Eduard E Martinez-Cáceres Eva María EM Arméstar Fernando F

Biomedicines 20230626 7

The reduction of mortality in patients with sepsis depends on the early identification and treatment of at-risk patients. The aim was to evaluate the HLA-DR expression on the surface of monocytes (<sub>M</sub>HLA-DR ratio), the sepsis index (CD64 expression on neutrophils/<sub>M</sub>HLA-DR ratio), and C-reactive protein (CRP) with the development of sepsis. We prospectively enrolled 77 critically ill patients, 59 with stroke and 18 with traumatic brain injuries. The biomarkers were tested at th ...[more]

PMID: 37509475

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Project description:BackgroundSustained yet intractable immunosuppression is commonly observed in septic patients, resulting in aggravated clinical outcomes. However, due to the substantial heterogeneity within septic patients, precise indicators in deciphering clinical trajectories and immunological alterations for septic patients remain largely lacking.MethodsWe adopted cross-species, single-cell RNA sequencing (scRNA-seq) analysis based on two published datasets containing circulating immune cell profile of septic patients as well as immune cell atlas of murine model of sepsis. Flow cytometry, laser scanning confocal microscopy (LSCM) imaging and Western blotting were applied to identify the presence of S100A9+ monocytes at protein level. To interrogate the immunosuppressive function of this subset, splenic monocytes isolated from septic wild-type or S100a9-/- mice were co-cultured with naïve CD4+ T cells, followed by proliferative assay. Pharmacological inhibition of S100A9 was implemented using Paquinimod via oral gavage.ResultsScRNA-seq analysis of human sepsis revealed substantial heterogeneity in monocyte compartments following the onset of sepsis, for which distinct monocyte subsets were enriched in disparate subclusters of septic patients. We identified a unique monocyte subset characterized by high expression of S100A family genes and low expression of human leukocyte antigen DR (HLA-DR), which were prominently enriched in septic patients and might exert immunosuppressive function. By combining single-cell transcriptomics of murine model of sepsis with in vivo experiments, we uncovered a similar subtype of monocyte significantly associated with late sepsis and immunocompromised status of septic mice, corresponding to HLA-DRlowS100Ahigh monocytes in human sepsis. Moreover, we found that S100A9+ monocytes exhibited profound immunosuppressive function on CD4+ T cell immune response and blockade of S100A9 using Paquinimod could partially reverse sepsis-induced immunosuppression.ConclusionsThis study identifies HLA-DRlowS100Ahigh monocytes correlated with immunosuppressive state upon septic challenge, inhibition of which can markedly mitigate sepsis-induced immune depression, thereby providing a novel therapeutic strategy for the management of sepsis.

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HLA-DR Expression on Monocytes and Sepsis Index Are Useful in Predicting Sepsis.

Publications

HLA-DR Expression on Monocytes and Sepsis Index Are Useful in Predicting Sepsis.

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