Monocyte human leukocyte antigen – Antigen D related, neutrophil oxidative burst and cytokine analysis in patients of decompensated cirrhosis with and without acute-on chronic liver failure

Satsangi, Sandeep; Duseja, Ajay; Sachdeva, M.P.; Tomer, Shallu; Arora, Sunil; Taneja, Sunil; Dhiman, Radha K.; Chawla, Yogesh

doi:10.1371/journal.pone.0200644

Cited by 8 publications

(9 citation statements)

References 24 publications

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“…In ACLF, expansion of HLA-DRLow monocytes was associated with poor clinical outcomes, with significantly lower HLA-DR expression in patients who died compared to those who survived (68). Similarly, the percentage of HLA-DR+ monocytes was significantly reduced patients with decompensated cirrhosis, both with and without ACLF (with alcohol as the commonest etiology in both cohorts), compared to healthy controls; and low HLA-DR expression was associated with death from ACLF (65). In a longitudinal study of critically ill cirrhotic patients, low HLA-DR expression at baseline was associated with mortality, and reduced further over time in non-survivors, compared to stable or increasing expression in survivors (69), suggesting impaired HLA-DR expression is reversible.…”

Section: Immunodeficiency In Advanced Cirrhosismentioning

confidence: 97%

Causes and Consequences of Innate Immune Dysfunction in Cirrhosis

et al. 2019

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Liver cirrhosis is an increasing health burden and public health concern. Regardless of etiology, patients with cirrhosis are at risk of a range of life-threatening complications, including the development of infections, which are associated with high morbidity and mortality and frequent hospital admissions. The term Cirrhosis-Associated Immune Dysfunction (CAID) refers to a dynamic spectrum of immunological perturbations that develop in patients with cirrhosis, which are intimately linked to the underlying liver disease, and negatively correlated with prognosis. At the two extremes of the CAID spectrum are systemic inflammation, which can exacerbate clinical manifestations of cirrhosis such as hemodynamic derangement and kidney injury; and immunodeficiency, which contributes to the high rate of infection in patients with decompensated cirrhosis. Innate immune cells, in particular monocytes/macrophages and neutrophils, are pivotal effector and target cells in CAID. This review focuses on the pathophysiological mechanisms leading to impaired innate immune function in cirrhosis. Knowledge of the phenotypic manifestation and pathophysiological mechanisms of cirrhosis associated immunosuppression may lead to immune targeted therapies to reduce susceptibility to infection in patients with cirrhosis, and better biomarkers for risk stratification, and assessment of efficacy of novel immunotherapies.

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Section: Immunodeficiency In Advanced Cirrhosismentioning

confidence: 97%

Causes and Consequences of Innate Immune Dysfunction in Cirrhosis

et al. 2019

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“…In addition, the spill-over of inflammatory mediators into the circulation of ACLF patients may contribute to neutrophil functional alterations. IL-6 and IL-8, the levels of which were significantly elevated in the plasma of patients with ACLF, are reported to prime resting neutrophils ( 29 ). Therefore, a combination of inflammatory and microbial signals may cause neutrophil functional reprogramming in HBV-ACLF patients.…”

Section: Discussionmentioning

confidence: 99%

Circulating Neutrophil Dysfunction in HBV-Related Acute-on-Chronic Liver Failure

Wu¹,

Sun²,

Wang³

et al. 2021

Front. Immunol.

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Background and AimsAcute-on-chronic liver failure (ACLF) is characterized by systemic inflammation accompanied by defective anti-bacterial immunity. The role of neutrophils in immune derangement of ACLF has not been fully elucidated. This study is aimed to characterize the role of circulating neutrophils in HBV-related ACLF patients.MethodsQuantitative, phenotypic, transcriptomic, and functional alterations of circulating neutrophils were compared in ACLF and non-ACLF subjects and analyzed for associations with short-term outcomes. Interventional experiments were performed to test the impact on ACLF-patient neutrophil function in vitro.ResultsCirculating absolute neutrophil count was significantly increased in patients with ACLF and was an independent risk factor for 28-day mortality. ACLF-patient neutrophils differentially expressed a panel of surface markers (include TLR-1, TLR-2, TLR-4, CEACAM-1 and FPR1), as well as a distinct transcriptomic signature. ACLF-neutrophils displayed significantly impaired phagocytosis but an increased capacity to form neutrophil extracellular traps (NETs), which was more pronounced in patients with poor outcome. Healthy neutrophils mimicked functional characteristics of ACLF counterpart after co-cultured with plasma from ACLF patients. The oxidative burst and cytokine production capacities remained unchanged. Plasma GM-CSF, IL-6, IL-8, IL-10, and IP-10 levels, as well as lipopolysaccharide (LPS) concentration, were markedly elevated in ACLF patients but not DAMP molecules HMGB-1 and HSP70. Finally, a glycolysis inhibitor, 2-deoxy-glucose, reduced NET formation of ACLF patients’ neutrophils.ConclusionsCirculating ACLF-patient neutrophils exhibit alterations in number, phenotype, gene expression and function, which was associated with poor outcome and shaped by the ACLF circulatory environment. Inhibiting glycolysis can reverse neutrophil dysfunction in ACLF patients.

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“…51 A substantial number of studies have since corroborated these findings. [52][53][54][55][56][57][58][59][60][61] Monocytes with reduced HLA-DR expression were shown to gradually decrease with severity of cirrhosis, 52,53,59,62 and were functionally linked to reduced production of TNF-a and IL-6 in response to LPS. 51,52,54,56,59,61 Some authors postulated a role for the anti-inflammatory cytokine IL-10 in monocyte modulation towards this "endotoxin tolerant" 63 population, 51,52,56,57,61 however, this mechanism likely involves multiple cytokines, endotoxins and cellular signals.…”

Section: Key Pointmentioning

confidence: 99%

Innate immune cells in cirrhosis

Bernsmeier

Merwe

Périanin

2020

Journal of Hepatology

138

121

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Cirrhosis is a multisystemic disease wherein inflammatory responses originating from advanced liver disease and its sequelae affect distant compartments. Patients with cirrhosis are susceptible to bacterial infections, which may precipitate acute decompensation and acute-on-chronic liver failure, both of which are associated with high short-term mortality. Innate immune cells are an essential first line of defence against pathogens. Activation of liver macrophages (Kupffer cells) and resident mastocytes generate proinflammatory and vaso-permeating mediators that induce accumulation of neutrophils, lymphocytes, eosinophils and monocytes in the liver, and promote tissue damage. During cirrhosis progression, damage-and pathogen-associated molecular patterns activate immune cells and promote development of systemic inflammatory responses which may involve different tissues and compartments. The antibacterial function of circulating neutrophils and monocytes is gradually and severely impaired as cirrhosis worsens, contributing to disease progression. The mechanisms underlying impaired antimicrobial responses are complex and incompletely understood. This review focuses on the continuous and distinct perturbations arising in innate immune cells during cirrhosis, including their impact on disease progression, as well as reviewing potential therapeutic targets.

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Monocyte human leukocyte antigen – Antigen D related, neutrophil oxidative burst and cytokine analysis in patients of decompensated cirrhosis with and without acute-on chronic liver failure

Cited by 8 publications

References 24 publications

Causes and Consequences of Innate Immune Dysfunction in Cirrhosis

Causes and Consequences of Innate Immune Dysfunction in Cirrhosis

Circulating Neutrophil Dysfunction in HBV-Related Acute-on-Chronic Liver Failure

Innate immune cells in cirrhosis

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