Immunomodulation in sepsis-why blunting the response doesn't work?

Szakmány, Tamás; Heurich, Meike

doi:10.1016/j.jinf.2015.04.019

Cited by 3 publications

(2 citation statements)

References 22 publications

(36 reference statements)

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“…This has been observed previously (131,134,135). Neutrophils and neutrophil NETs may play a key role in intravascular coagulation, which is a feature of sepsis (136,137) and also be involved in immunomodulation (138)(139)(140)(141)(142)(143).Therapies targeting these cells may be beneficial in sepsis (144,145), although their role as disease driver or modulator remains unclear. As there are both pro and antiinflammatory responses evident in sepsis, the pathway toward immunomodulatory therapies based on these observations, is still unclear (146).…”

Section: Cd177mentioning

confidence: 60%

Development of a Bioinformatics Framework for Identification and Validation of Genomic Biomarkers and Key Immunopathology Processes and Controllers in Infectious and Non-infectious Severe Inflammatory Response Syndrome

et al. 2020

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Sepsis is defined as dysregulated host response caused by systemic infection, leading to organ failure. It is a life-threatening condition, often requiring admission to an intensive care unit (ICU). The causative agents and processes involved are multifactorial but are characterized by an overarching inflammatory response, sharing elements in common with severe inflammatory response syndrome (SIRS) of non-infectious origin. Sepsis presents with a range of pathophysiological and genetic features which make clinical differentiation from SIRS very challenging. This may reflect a poor understanding of the key gene inter-activities and/or pathway associations underlying these disease processes. Improved understanding is critical for early differential recognition of sepsis and SIRS and to improve patient management and clinical outcomes. Judicious selection of gene biomarkers suitable for development of diagnostic tests/testing could make differentiation of sepsis and SIRS feasible. Here we describe a methodologic framework for the identification and validation of biomarkers in SIRS, sepsis and septic shock patients, using a 2-tier gene screening, artificial neural network (ANN) data mining technique, using previously published gene expression datasets. Eight key hub markers have been identified which may delineate distinct, core disease processes and which show potential for informing underlying immunological and pathological processes and thus patient stratification and treatment. These do not show sufficient fold change differences between the different disease states to be useful as primary diagnostic biomarkers, but are instrumental in identifying candidate pathways and other associated biomarkers for further exploration.

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Section: Cd177mentioning

confidence: 60%

Development of a Bioinformatics Framework for Identification and Validation of Genomic Biomarkers and Key Immunopathology Processes and Controllers in Infectious and Non-infectious Severe Inflammatory Response Syndrome

et al. 2020

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“…Some evidence indicates that IgM-enriched therapy may be beneficial in Gram-negative sepsis, however the data is conflicting [32][33][34]. Unknown mechanisms of action of both endogenous immunoglobulins and immunoglobulin preparations in sepsis could explain the controversial results found in clinical trials [35].…”

Section: Introductionmentioning

confidence: 99%

Plasma IgM Levels Differentiate between Survivors and Non-Survivors of Culture-Positive and Culture-Negative Sepsis and SIRS: A Pilot Study

Pathare

Szakmány

Hall

et al. 2021

JCM

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Immunoglobulin IgM is important for controlling viral and bacterial infections, and low immunoglobulin levels have been found in sepsis. There is a clear need to stratify sepsis patients according to the presence of an invading organism, compared to no organism identified, and SIRS patients, where organ dysfunction is a result of a non-infective process. The aim of this pilot study in a small cohort of patients with sepsis was to evaluate the association between IgM plasma levels and survival in 47 patients with sepsis and 11 patients diagnosed with organ failure without the identification of a pathogen (SIRS). Patients were admitted to the intensive care unit (ICU) at The Royal Glamorgan Hospital, Llantrisant, UK between 2010 and 2014. We found that low IgM levels were associated with sepsis, but not SIRS. IgM levels did not differ significantly for culture-positive (CP) compared with culture-negative (CN, no organism found) sepsis samples. Kaplan–Meier analysis was used to compare survival curves according to IgM levels, with no significant difference. We observed significantly higher survival in the CP samples when comparing with CN. Cut-off value for IgM (266 μg/mL) for diagnosis of sepsis patients was determined using receiver operator characteristic (ROC) curves with 70% sensitivity, 69% specificity and 92% negative predictive values (NPV), respectively. The corresponding area under the curve (AUC) for the discrimination of sepsis patients was AUC = 0.73, and in a subgroup analysis of CP was AUC = 0.77 and for CN was AUC = 0.79. We confirm IgM as a good diagnostic marker of sepsis. These findings indicate a difference in the pathology between culture-positive versus negative sepsis, SIRS and survival. This indicates that IgM is likely relevant to pathology, because of its role in the early immune response against pathogens, the potentially protective role of natural IgM antibodies, and supports its application in immunoglobulin therapy.

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The search for biomarkers in the critically ill: a cautionary tale

Moran,

Solomon

2018

Critical Care and Resuscitation

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Immunomodulation in sepsis-why blunting the response doesn't work?

Cited by 3 publications

References 22 publications

Development of a Bioinformatics Framework for Identification and Validation of Genomic Biomarkers and Key Immunopathology Processes and Controllers in Infectious and Non-infectious Severe Inflammatory Response Syndrome

Development of a Bioinformatics Framework for Identification and Validation of Genomic Biomarkers and Key Immunopathology Processes and Controllers in Infectious and Non-infectious Severe Inflammatory Response Syndrome

Plasma IgM Levels Differentiate between Survivors and Non-Survivors of Culture-Positive and Culture-Negative Sepsis and SIRS: A Pilot Study

The search for biomarkers in the critically ill: a cautionary tale

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