Interrogating the sepsis host immune response using cytomics

Lindell, Robert B.; Meyer, Nuala J.

doi:10.1186/s13054-023-04366-0

Cited by 3 publications

(2 citation statements)

References 51 publications

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“…The immune system exerts a crucial role in critical illness and has become a research hotspot 32 . Immunosuppression is an outstanding characteristic of sepsis, and reversing sepsis-induced immunosuppression might be an alternative strategy for sepsis treatment 33 .…”

Section: Discussionmentioning

confidence: 99%

Basophils absence predicts poor prognosis and indicates immunosuppression of patients in intensive care units

Chen,

Zhu,

Zhuo

et al. 2023

Sci Rep

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Immune cells and immunity are associated with the prognosis of patients with critical illness. Here, medical records retrospectively extracted from the Medical Information Mart for Intensive Care IV were used for screening an immune-related biomarker in intensive care units (ICU) patients and applied for validating the identified indicator in septic patients. In this work, the count of innate immune cells, basophils, harbored a superior role in predicting ICU patients’ prognosis compared with those of other blood immune cells (OR 0.013, 95% CI 0.001, 0.118, P < 0.001). Importantly, basophils absence during ICU stay was positively correlated with the 28-day mortality of ICU patients and served as an independent predictor of ICU patients’ prognosis (OR 3.425, 95% CI 3.717–3.165, P < 0.001). Moreover, the association between critical illness progression, poor outcome, and basophils absence was verified in septic patients. Subsequent investigations revealed the positive relationship between basophils absence and immunosuppression, and suggested the potential of basophils-mediated immunity in predicting the 28-day mortality of ICU patients. Collectively, we identify basophils absence during ICU stay as a novel and unfavorable indicator for evaluating the prognosis of ICU patients and recognizing a branch of ICU patients potentially suitable for intensified treatment and immunoenhancement therapy.

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Section: Discussionmentioning

confidence: 99%

Basophils absence predicts poor prognosis and indicates immunosuppression of patients in intensive care units

Chen,

Zhu,

Zhuo

et al. 2023

Sci Rep

View full text Add to dashboard Cite

show abstract

“…T lymphocytes also have been described to overexpress inhibitory markers such as T cell immunoglobulin and mucin-domain-containing protein 1 (TIM-1), lymphocyte activation gene 3 (LAG-3), and cytotoxic T-lymphocyte-associated protein 4 (CTLA4). T cell hyperactivation was also noticeable in afflicted patients: either through antigen-dependent activation or through an antigen-independent “bystander” activation [ 10 ].…”

Section: Cytomicsmentioning

confidence: 99%

The Omics Complexity in Sepsis: The Limits of the Personalized Medicine Approach

Isac,

Tanasescu

et al. 2024

JPM

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Sepsis is one of the most common causes of morbidity and mortality worldwide. Despite the remarkable advances in modern medicine throughout the last century, the mortality rates associated with sepsis have remained significantly elevated, both in high- and low-income countries. The main difficulty in the diagnosis and treatment of septic patients is the tremendous heterogeneity of this condition. The vast heterogeneity that characterizes sepsis ranges from the clinical presentation to the biological aspects of the disease. Evidence-based medicine approaches sepsis as a homogenous syndrome and does not consider the individual discrepancies between septic patients. This approach may contribute to the poor outcomes of septic patients. In recent years, personalized medicine has gained significant interest. This novel form of medicine underlines the importance of understanding the genetic, epigenetic, and molecular basis of a disease in order to provide a more tailored approach for the patient. The study of “omics”, such as cytomics, genomics, epigenomics, transcriptomics, proteomics, and metabolomics, provides a deeper comprehension of the complex interactions between the host, the disease, and the environment. The aim of this review is to summarize the potential role of a personalized approach in sepsis management, considering the interactions between various “omics”.

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Dysregulated STAT3 signaling and T cell immunometabolic dysfunction define a targetable, high mortality subphenotype of critically ill children

Lindell,

Sayed,

Campos

et al. 2024

Preprint

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Sepsis is the leading cause of death of hospitalized children worldwide. Despite the established link between immune dysregulation and mortality in pediatric sepsis, it remains unclear which host immune factors contribute causally to adverse sepsis outcomes. Identifying modifiable pathobiology is an essential first step to successful translation of biologic insights into precision therapeutics. We designed a prospective, longitudinal cohort study of 88 critically ill pediatric patients with multiple organ dysfunction syndrome (MODS), including patients with and without sepsis, to define subphenotypes associated with targetable mechanisms of immune dysregulation. We first assessed plasma proteomic profiles and identified shared features of immune dysregulation in MODS patients with and without sepsis. We then employed consensus clustering to define three subphenotypes based on protein expression at disease onset and identified a strong association between subphenotype and clinical outcome. We next identified differences in immune cell frequency and activation state by MODS subphenotype and determined the association between hyperinflammatory pathway activation and cellular immunophenotype. Using single cell transcriptomics, we demonstrated STAT3 hyperactivation in lymphocytes from the sickest MODS subgroup and then identified an association between STAT3 hyperactivation and T cell immunometabolic dysregulation. Finally, we compared proteomics findings between patients with MODS and patients with inborn errors of immunity that amplify cytokine signaling pathways to further assess the impact of STAT3 hyperactivation in the most severe patients with MODS. Overall, these results identify a potentially pathologic and targetable role for STAT3 hyperactivation in a subset of pediatric patients with MODS who have high severity of illness and poor prognosis.

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Interrogating the sepsis host immune response using cytomics

Cited by 3 publications

References 51 publications

Basophils absence predicts poor prognosis and indicates immunosuppression of patients in intensive care units

Basophils absence predicts poor prognosis and indicates immunosuppression of patients in intensive care units

The Omics Complexity in Sepsis: The Limits of the Personalized Medicine Approach

Dysregulated STAT3 signaling and T cell immunometabolic dysfunction define a targetable, high mortality subphenotype of critically ill children

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