Persistence of neutrophil extracellular traps and anticardiolipin auto‐antibodies in post‐acute phase COVID‐19 patients

Journal of Medical Virology, Год журнала: 2022, Номер 95(1)

Опубликована: Окт. 13, 2022

In the early phase of pandemic, we were among first to postulate that neutrophil extracellular traps (NETs) play a key role in COVID-19 pathogenesis. This exploratory prospective study based on 279 individuals showed plasma levels elastase, myeloperoxidase and circulating DNA nuclear mitochondrial origins nonsevere (NS), severe (S) postacute (PAP) patients statistically different as compared healthy individuals, revealed high diagnostic power these NETs markers respect disease severity. The NE, MPO, cir-nDNA determined by Area Under Receiver Operating Curves (AUROC) was 0.95, 097, 0.64; 0.99, 1.0, 0.82; 0.94, 0.93, NS, S, PAP patient subgroups, respectively. addition, significant fraction S well exhibited aCL IgM/IgG anti-B2GP positivity. We demonstrate persistence consequently sustained innate immune response imbalance, prolonged low-level pro-thrombotic potential activity highlighting need monitor all investigate pathogenesis following intensive care, better identify which medical resources will ensure complete recovery.

Язык: Английский

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A randomised trial of anti-GM-CSF otilimab in severe COVID-19 pneumonia (OSCAR)

European Respiratory Journal, Год журнала: 2022, Номер 61(2), С. 2101870 - 2101870

Опубликована: Окт. 13, 2022

Granulocyte-macrophage colony-stimulating factor (GM-CSF) and dysregulated myeloid cell responses are implicated in the pathophysiology severity of COVID-19.

Язык: Английский

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Metabolic reprograming shapes neutrophil functions in severe COVID‐19

European Journal of Immunology, Год журнала: 2021, Номер 52(3), С. 484 - 502

Опубликована: Дек. 6, 2021

To better understand the mechanisms at basis of neutrophil functions during SARS-CoV-2, we studied patients with severe COVID-19 pneumonia. They had high blood proportion degranulated neutrophils and elevated plasma levels myeloperoxidase (MPO), elastase, MPO-DNA complexes, which are typical markers extracellular traps (NET). Their display dysfunctional mitochondria, defective oxidative burst, increased glycolysis, glycogen accumulation in cytoplasm, increase glycogenolysis. Hypoxia-inducible factor 1α (ΗΙF-1α) is stabilized such cells, it controls level phosphorylase L (PYGL), a key enzyme Inhibiting PYGL abolishes ability to produce NET. Patients displayed significant increases molecules involved regulation neutrophils' function including CCL2, CXCL10, CCL20, IL-18, IL-3, IL-6, G-CSF, GM-CSF, IFN-γ. Our data suggest that metabolic remodelling vital for formation NET boosting inflammatory response, thus, suggesting modulating ΗΙF-1α or could represent novel approach innovative therapies.

Язык: Английский

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Mechanism for the attenuation of neutrophil and complement hyperactivity by MSC exosomes

Cytotherapy, Год журнала: 2022, Номер 24(7), С. 711 - 719

Опубликована: Фев. 15, 2022

Complements and neutrophils are two key players of the innate immune system that widely implicated as drivers severe COVID-19 pathogenesis, evident by direct correlation respiratory failure mortality with elevated levels terminal complement complex C5b-9 neutrophils. In this study, we identified a feed-forward loop between complements could amplify perpetuate cytokine storm seen in SARS-CoV-2-infected patients. We observed for first time activation directly triggered neutrophil extracellular trap (NET) release interleukin (IL)-17 production This is also report NETs IL-17 induced assembly on be abrogated mesenchymal stem cell (MSC) exosomes. Neutralizing anti-CD59 antibodies abolished abrogation. Based our findings, hypothesize MSC exosomes alleviate dysregulation acute failure, such patients, inhibiting through exosomal CD59, thereby disrupting to inhibit amplification perpetuation inflammation during SARS-CoV-2 infection.

Язык: Английский

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Physiological and Pathophysiological Roles of Metabolic Pathways for NET Formation and Other Neutrophil Functions

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Фев. 9, 2022

Neutrophils are the most numerous cells in leukocyte population and essential for innate immunity. To limit their effector functions, neutrophils able to modulate glycolysis other cellular metabolic pathways. These pathways not only energy usage, but also specialized actions, such as production of reactive oxygen species (ROS), chemotaxis, phagocytosis, degranulation, formation neutrophil extracellular traps (NETs). It has been demonstrated that activated viable can produce NETs, which consists a DNA scaffold bind granule proteins microorganisms. The NETs requires availability increased amounts adenosine triphosphate (ATP) it is an active therefore energy-dependent process. In this article, we discuss glycolytic routes association with functions focusing on role building up space. A better understanding requirements may lead discovery molecular targets suitable develop novel anti-infectious and/or anti-inflammatory drugs.

Язык: Английский

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Mechanistic Understanding of Lung Inflammation: Recent Advances and Emerging Techniques

Journal of Inflammation Research, Год журнала: 2022, Номер Volume 15, С. 3501 - 3546

Опубликована: Июнь 1, 2022

Abstract: Acute respiratory distress syndrome (ARDS) is a life-threatening lung injury characterized by an acute inflammatory response in the parenchyma. Hence, it considered as most appropriate clinical to study pathogenic mechanisms of inflammation. ARDS associated with increased morbidity and mortality intensive care unit (ICU), while no effective pharmacological treatment exists. It very important therefore fully characterize underlying pathobiology related mechanisms, order develop novel therapeutic approaches. In vivo vitro models are pre-clinical tools biological medical research mechanistic pathological understanding majority diseases. this review, we will present data from selected experimental injury/acute inflammation, which have been based on disorders that can lead development processes humans, including ventilation-induced (VILI), sepsis, ischemia/reperfusion, smoke, acid aspiration, radiation, transfusion-related (TRALI), influenza, Streptococcus ( S .) pneumoniae coronaviruses infection. Data corresponding conditions also be presented. The inflammation covered oxidative stress, neutrophil extracellular traps, mitogen-activated protein kinase (MAPK) pathways, surfactant, water ion channels. Finally, brief overview emerging techniques field omics applied research, encompassing genomics, transcriptomics, proteomics, metabolomics, may recognize factors help stratify ICU patients at risk, predict their prognosis, possibly, serve more specific targets. Keywords: syndrome, biomarkers,

Язык: Английский

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A new hope? Possibilities of therapeutic IgA antibodies in the treatment of inflammatory lung diseases

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Март 27, 2023

Inflammatory lung diseases represent a persistent burden for patients and the global healthcare system. The combination of high morbidity, (partially) mortality limited innovations in last decades, have resulted great demand new therapeutics. Are therapeutic IgA antibodies possibly hope treatment inflammatory diseases? Current research increasingly unravels elementary functions as protector against infections modulator overwhelming inflammation. With focus on IgA, this review describes pathological alterations mucosal immunity how they contribute to chronic inflammation most common diseases. current knowledge circulation, particularly respiratory mucosa, are summarized. interplay between neutrophils seems be key control In addition, hurdles benefits antibodies, well currently known clinically used preparations described. data highlighted here, together with upcoming strategies aiming at circumventing pitfalls may pave way promising antibody class application

Язык: Английский

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Short term outcomes of COVID-19 in lupus: Propensity score matched analysis from a nationwide multi-centric research network

Journal of Autoimmunity, Год журнала: 2021, Номер 125, С. 102730 - 102730

Опубликована: Окт. 11, 2021

Язык: Английский

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CD8+ T Cells in SARS-CoV-2 Induced Disease and Cancer—Clinical Perspectives

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Апрель 1, 2022

Dysregulated innate and adaptive immunity is a sign of SARS-CoV-2-induced disease cancer. CD8 + T cells are important the immune system. The belong to take front-line defense against viral infections Extreme T-cell activities in lung patients with within tumor microenvironment (TME) will change their functionality into exhausted state undergo apoptosis. Such diminished put cancer cases at high-risk group for disease, rendering sepsis more severe condition which finally cause higher rate mortality. Recovering responses from purpose vaccination SARS-CoV-2. aim this review discuss cellular present some strategies recovering these critical cells.

Язык: Английский

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Proteomic analysis identifies a signature of disease severity in the plasma of COVID-19 pneumonia patients associated to neutrophil, platelet and complement activation

Clinical Proteomics, Год журнала: 2022, Номер 19(1)

Опубликована: Ноя. 8, 2022

Abstract Most patients infected with SARS-CoV-2 display mild symptoms good prognosis, while 20% of suffer from severe viral pneumonia and up to 5% may require intensive care unit (ICU) admission due acute respiratory syndrome, which could be accompanied by multiorgan failure. Plasma proteomics provide valuable unbiased information about disease progression therapeutic candidates. Recent proteomic studies have identified molecular changes in plasma COVID-19 that implied significant dysregulation several aspects the inflammatory response a general metabolic suppression. However, these alterations are associated severity remains only partly characterized. A known limitation samples is large difference macromolecule abundance, concentration spanning at least 10 orders magnitude. To improve coverage contents, we performed deep analysis severe/fatal compared who did not ICU (non-ICU). this aim, were first depleted most abundant proteins, trypsin digested peptides subjected high pH reversed-phase peptide fractionation before LC–MS analysis. These results highlighted an increase proteins involved neutrophil platelet activity phase response, significantly higher when non-ICU ones. Importantly, selective induction complement cascade factors patients. Data available via ProteomeXchange identifier PXD036491. Among alterations, confirmed ELISA levels granule DEFA3 LCN2 present requiring healthy donors. Altogether, our study provided in-depth view proteome occur relation severity, can helpful identify strategies outcome.

Язык: Английский

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