scholarly journals Prothrombotic antiphospholipid antibodies in COVID-19

2020 ◽  
Author(s):  
Yu Zuo ◽  
Shanea K. Estes ◽  
Alex A. Gandhi ◽  
Srilakshmi Yalavarthi ◽  
Ramadan A. Ali ◽  
...  
Keyword(s):  
Antiphospholipid Antibodies ◽  
Case Series ◽  
Neutrophil Extracellular Traps ◽  
Significant Percentage ◽  
Small Vessels ◽  
Extracellular Traps ◽  
Glycoprotein I ◽  
Lung Histopathology ◽  
Life Threatening ◽  
Net Release

ABSTRACTPatients with coronavirus disease 19 (COVID-19) are at high risk for thrombotic arterial and venous occlusions. At the same time, lung histopathology often reveals fibrin-based occlusion of small vessels in patients who succumb to the disease. Antiphospholipid syndrome (APS) is an acquired and potentially life-threatening thrombophilia in which patients develop pathogenic autoantibodies (aPL) targeting phospholipids and phospholipid-binding proteins. Small case series have recently detected aPL in patients with COVID-19. Here, we measured eight types of aPL (anticardiolipin IgG/IgM/IgA, anti-beta-2 glycoprotein I IgG/IgM/IgA, and anti-phosphatidylserine/prothrombin (PS/PT) IgG/IgM) in the sera of 172 patients hospitalized with COVID-19. We detected anticardiolipin IgM antibodies in 23%, anti-PS/PT IgG in 24%, and anti-PS/PT IgM in 18%. Any aPL was present in 52% of patients using the manufacturer’s threshold and in 30% using a more stringent cutoff (≥40 units). Higher levels of aPL were associated with neutrophil hyperactivity (including the release of neutrophil extracellular traps/NETs), higher platelet count, more severe respiratory disease, and lower glomerular filtration rates. Similar to patients with known and longstanding APS, IgG fractions isolated from patients with COVID-19 promoted NET release from control neutrophils. Furthermore, injection of these COVID-19 IgG fractions into mice accelerated venous thrombosis. Taken together, these studies suggest that a significant percentage of patients with COVID-19 become at least transiently positive for aPL and that these aPL are potentially pathogenic.

scholarly journals Prothrombotic autoantibodies in serum from patients hospitalized with COVID-19

2020 ◽  
Vol 12 (570) ◽  
pp. eabd3876 ◽  
Author(s):  
Yu Zuo ◽  
Shanea K. Estes ◽  
Ramadan A. Ali ◽  
Alex A. Gandhi ◽  
Srilakshmi Yalavarthi ◽  
...  
Keyword(s):  
Antiphospholipid Syndrome ◽  
Estimated Glomerular Filtration Rate ◽  
Case Series ◽  
Healthy Individuals ◽  
Serum Samples ◽  
Extracellular Traps ◽  
Glycoprotein I ◽  
Lung Histopathology ◽  
Life Threatening ◽  
Net Release

Patients with COVID-19 are at high risk for thrombotic arterial and venous occlusions. Lung histopathology often reveals fibrin-based blockages in the small blood vessels of patients who succumb to the disease. Antiphospholipid syndrome is an acquired and potentially life-threatening thrombophilia in which patients develop pathogenic autoantibodies targeting phospholipids and phospholipid-binding proteins (aPL antibodies). Case series have recently detected aPL antibodies in patients with COVID-19. Here, we measured eight types of aPL antibodies in serum samples from 172 patients hospitalized with COVID-19. These aPL antibodies included anticardiolipin IgG, IgM, and IgA; anti–β2 glycoprotein I IgG, IgM, and IgA; and anti-phosphatidylserine/prothrombin (aPS/PT) IgG and IgM. We detected aPS/PT IgG in 24% of serum samples, anticardiolipin IgM in 23% of samples, and aPS/PT IgM in 18% of samples. Antiphospholipid autoantibodies were present in 52% of serum samples using the manufacturer’s threshold and in 30% using a more stringent cutoff (≥40 ELISA-specific units). Higher titers of aPL antibodies were associated with neutrophil hyperactivity, including the release of neutrophil extracellular traps (NETs), higher platelet counts, more severe respiratory disease, and lower clinical estimated glomerular filtration rate. Similar to IgG from patients with antiphospholipid syndrome, IgG fractions isolated from patients with COVID-19 promoted NET release from neutrophils isolated from healthy individuals. Furthermore, injection of IgG purified from COVID-19 patient serum into mice accelerated venous thrombosis in two mouse models. These findings suggest that half of patients hospitalized with COVID-19 become at least transiently positive for aPL antibodies and that these autoantibodies are potentially pathogenic.

scholarly journals The state of art of neutrophil extracellular traps in protozoan and helminthic infections

2019 ◽  
Vol 39 (1) ◽  
Author(s):  
César Díaz-Godínez ◽  
Julio C. Carrero
Keyword(s):  
Neutrophil Extracellular Traps ◽  
Parasitic Infections ◽  
Parasitic Diseases ◽  
Helminth Parasites ◽  
Extracellular Traps ◽  
Helminthic Infections ◽  
Bacteria And Fungi ◽  
Net Release

AbstractNeutrophil extracellular traps (NETs) are DNA fibers associated with histones, enzymes from neutrophil granules and anti-microbial peptides. NETs are released in a process denominated NETosis, which involves sequential steps that culminate with the DNA extrusion. NETosis has been described as a new mechanism of innate immunity related to defense against different pathogens. The initial studies of NETs were carried out with bacteria and fungi, but currently a large variety of microorganisms capable of inducing NETs have been described including protozoan and helminth parasites. Nevertheless, we have little knowledge about how NETosis process is carried out in response to the parasites, and about its implication in the resolution of this kind of disease. In the best case, the NETs entrap and kill parasites in vitro, but in others, immobilize the parasites without affecting their viability. Moreover, insufficient studies on the NETs in animal models of infections that would help to define their role, and the association of NETs with chronic inflammatory pathologies such as those occurring in several parasitic infections have left open the possibility of NETs contributing to pathology instead of protection. In this review, we focus on the reported mechanisms that lead to NET release by protozoan and helminth parasites and the evidence that support the role of NETosis in the resolution or pathogenesis of parasitic diseases.

NETosis: how vital is it?

Blood ◽  
2013 ◽  
Vol 122 (16) ◽  
pp. 2784-2794 ◽  
Author(s):  
Bryan G. Yipp ◽  
Paul Kubes
Keyword(s):  
Innate Immunity ◽  
Cell Death ◽  
Critical Role ◽  
Neutrophil Extracellular Traps ◽  
Live Cell ◽  
Extracellular Traps ◽  
Cell Death Pathway ◽  
A Cell ◽  
Net Release

Abstract In this review, we examine the evidence that neutrophil extracellular traps (NETs) play a critical role in innate immunity. We summarize how NETs are formed in response to various stimuli and provide evidence that NETosis is not universally a cell death pathway. Here we describe at least 2 different mechanisms by which NETs are formed, including a suicide lytic NETosis and a live cell or vital NETosis. We also evaluate the evidence for NETs in catching and killing pathogens. Finally, we examine how infections are related to the development of autoimmune and vasculitic diseases through unintended but detrimental bystander damage resulting from NET release.

scholarly journals Life-threatening COVID-19 presenting as stroke with antiphospholipid antibodies and low ADAMTS-13 activity, and the role of therapeutic plasma exchange: A case series

2020 ◽  
Vol 8 ◽  
pp. 2050313X2096408
Author(s):  
Abdulrahman Alharthy ◽  
Fahad Faqihi ◽  
Abdullah Balhamar ◽  
Ziad A Memish ◽  
Dimitrios Karakitsos
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Plasma Exchange ◽  
Plasma Volume ◽  
Antiphospholipid Antibodies ◽  
Rescue Therapy ◽  
Antiviral Treatment ◽  
Case Series ◽  
Therapeutic Plasma Exchange ◽  
Life Threatening

We present a case series of three patients with COVID-19 who were admitted to our intensive care unit due to acute respiratory distress syndrome, brain infarction, pulmonary embolism, and antiphospholipid antibodies. We applied therapeutic plasma exchange on all cases. On intensive care unit admission, all patients had low (<10) Glasgow Coma Scale, and central nervous imaging showed multiple brain infarctions. COVID-19 was confirmed by reverse transcriptase polymerase chain reaction assays. Patients underwent rescue therapeutic plasma exchange using the Spectra OptiaTM Apheresis System (Terumo BCT Inc., USA), which operates with acid-citrate dextrose anticoagulant as per Kidney Disease Improving Global Outcomes 2019 guidelines. A dose of 1.5 plasma volume was used for the first dose and then 1 plasma volume daily for a total of five doses. Plasma was replaced with Octaplas LG® (Octapharma AG, USA), which is an artificial fresh frozen plasma product that has undergone viral inactivation by prion reduction technology. We administered ARDS-net/prone positioning ventilation, empiric antiviral treatment, therapeutic anticoagulation, and intensive care unit supportive care. Laboratory tests showed lymphocytopenia; elevated levels of D-dimer, fibrinogen, total bilirubin, C-reactive protein, lactate dehydrogenase, and ferritin; as well as low levels of ADAMTS-13 activity and antibody. Serology tests depicted positive IgM and IgG antiphospholipid antibodies (anti-cardiolipin and anti-β2-glycoprotein I antibodies). No side effects of therapeutic plasma exchange were recorded. After the completion of therapeutic plasma exchange, patients improved clinically and gradually recovered neurologically (after 27–32 days). To conclude, in life-threatening COVID-19, especially when immune dysregulation features such as antiphospholipid antibodies exist, therapeutic plasma exchange could be an effective rescue therapy.

scholarly journals Neutrophil Extracellular Traps and Microcrystals

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Balázs Rada
Keyword(s):  
Early Stage ◽  
Neutrophil Extracellular Traps ◽  
Calcium Pyrophosphate ◽  
Cholesterol Crystals ◽  
Extracellular Traps ◽  
Calcium Pyrophosphate Dehydrate ◽  
Innate Immune Mechanism ◽  
Silica Crystals ◽  
Net Release ◽  
Urate Crystals

Neutrophil extracellular traps represent a fascinating mechanism by which PMNs entrap extracellular microbes. The primary purpose of this innate immune mechanism is thought to localize the infection at an early stage. Interestingly, the ability of different microcrystals to induce NET formation has been recently described. Microcrystals are insoluble crystals with a size of 1–100 micrometers that have different composition and shape. Microcrystals have it in common that they irritate phagocytes including PMNs and typically trigger an inflammatory response. This review is the first to summarize observations with regard to PMN activation and NET release induced by microcrystals. Gout-causing monosodium urate crystals, pseudogout-causing calcium pyrophosphate dehydrate crystals, cholesterol crystals associated with atherosclerosis, silicosis-causing silica crystals, and adjuvant alum crystals are discussed.

scholarly journals Coronavirus disease 2019 (COVID-19): NETosis-associated mechanisms of progression and prospects for therapy regulating the formation of neutrophil extracellular traps (NETs)

2021 ◽  
Vol 6 (4) ◽  
pp. 64-73
Author(s):  
K. A. Aitbaev ◽  
I. T. Murkamilov ◽  
V. V. Fomin ◽  
I. O. Kudaibergenova ◽  
F. A. Yusupov
Keyword(s):  
Molecular Mechanisms ◽  
Adverse Reactions ◽  
Thrombus Formation ◽  
The Elderly ◽  
Neutrophil Extracellular Traps ◽  
The Body ◽  
Surrounding Tissue ◽  
Chronic Respiratory Diseases ◽  
Small Vessels ◽  
Extracellular Traps

Infectious disease COVID-19 caused by the SARS-CoV-2 coronavirus is characterized by high contagiousness, complexity of pathogenesis and unpredictability of the clinical course. In severe cases, which are especially susceptible to men, the elderly and people with underlying medical conditions such as obesity, diabetes, hypertension, cardiovascular and chronic respiratory diseases, the infection leads to respiratory failure and death due to the development of an extensive inflammatory reaction. As a result of many studies, it has been established that one of the leading causes of the severe course and death of patients with COVID-19 is the development of coagulopathy, that is, increased thrombus formation in small vessels due to excessive activity of neutrophils, which form the so-called neutrophil extracellular traps (NETs). Although NETs play a useful role in protecting their host from pathogens, their overgrowth can trigger a cascade of adverse reactions including: the production of antibodies against the host’s DNA (autoimmunization); damage to surrounding tissue; or the occurrence of thromboembolic complications. Therefore, extracellular neutrophil traps and their markers have been identified as targets for new therapeutic strategies aimed at reducing the severity of COVID-19 disease and/or mortality. This article describes the structure of NETs, as well as analyzes the molecular mechanisms that contribute to their overgeneration. In addition, the prospects for COVID-19 therapy aimed at regulating the formation of extracellular traps by creating drugs both limiting the production of NET structures and dissolving their excess amounts in the body of patients are discussed.

scholarly journals Assessment of Neutrophil Extracellular Traps in Coronary Thrombus of a Case Series of Patients With COVID-19 and Myocardial Infarction

2020 ◽  
Author(s):  
Ana Blasco ◽  
María-José Coronado ◽  
Fernando Hernández-Terciado ◽  
Paloma Martín ◽  
Ana Royuela ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Case Series ◽  
Neutrophil Extracellular Traps ◽  
Extracellular Traps ◽  
Coronary Thrombus

scholarly journals Neutrophil extracellular traps and thrombosis in COVID-19

2020 ◽  
Author(s):  
Yu Zuo ◽  
Melanie Zuo ◽  
Srilakshmi Yalavarthi ◽  
Kelsey Gockman ◽  
Jacqueline A. Madison ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Histone H3 ◽  
Neutrophil Extracellular Traps ◽  
Neutrophil Extracellular Trap ◽  
Dna Complexes ◽  
Extracellular Traps ◽  
Free Dna ◽  
Extracellular Trap ◽  
Net Release ◽  
D Dimer

ABSTRACTHere, we report on four patients whose hospitalizations for COVID-19 were complicated by venous thromboembolism (VTE). All demonstrated high levels of D-dimer as well as high neutrophil-to-lymphocyte ratios. For three patients, we were able to test sera for neutrophil extracellular trap (NET) remnants and found significantly elevated levels of cell-free DNA, myeloperoxidase-DNA complexes, and citrullinated histone H3. Neutrophil-derived S100A8/A9 (calprotectin) was also elevated. Given strong links between hyperactive neutrophils, NET release, and thrombosis in many inflammatory diseases, the potential relationship between NETs and VTE should be further investigated in COVID-19.

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