Anti‐β2GPI/β2GPI induces human neutrophils to generate NETs by relying on ROS

You, Yanqiu; Liu, Yanhong; Li, Fujun; Mu, Fengyun; Zha, Caijun

doi:10.1002/cbf.3363

Cited by 13 publications

(12 citation statements)

References 29 publications

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“…In SLE, LDGs are associated with vascular damage (43, 58) and with disease activity in juvenile lupus (59). In APS, LDGs are enriched especially in patients with high titers of anti-β2-glycoprotein-I (60), antibodies capable of inducing NETosis (61, 62).…”

Section: Neutrophils and Their Effector Functions In Sle And Apsmentioning

confidence: 99%

“…Similarly, patients with primary APS also display enhanced spontaneous NET release (62). Plasma of patients with APS (both primary and secondary) as well as aPL alone can induce NETs from healthy neutrophils (61, 138), and NET release correlates with circulating levels of aPL (62). Deposition of NETs can be found in intervillous tissue of pre-eclampsia pregnancies (139), possibly contributing to the pregnancy morbidities present in APS.…”

Section: Neutrophils and Their Effector Functions In Sle And Apsmentioning

confidence: 99%

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Neutrophils—Important Communicators in Systemic Lupus Erythematosus and Antiphospholipid Syndrome

et al. 2019

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Systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) are two autoimmune diseases that can occur together or separately. Insights into the pathogenesis have revealed similarities, such as development of autoantibodies targeting subcellular antigens as well as a shared increased risk of cardiovascular morbidity, potentially due to mutual pathologic mechanisms. In this review, we will address the evidence implicating neutrophils in the pathogenesis of these conditions, highlighting their shared features. The neutrophil is the most abundant leukocyte, recognized for its role in infectious and inflammatory diseases, but dysregulation of neutrophil effector functions, including phagocytosis, oxidative burst and formation of neutrophil extracellular traps (NETs) may also contribute to an autoimmune process. The phenotype of neutrophils in SLE and APS differs from neutrophils of healthy individuals, where neutrophils in SLE and APS are activated and prone to aggregate. A specific subset of low-density neutrophils with different function compared to normal-density neutrophils can also be found within the peripheral blood mononuclear cell (PBMC) fraction after density gradient centrifugation of whole blood. Neutrophil phagocytosis is required for regular clearance of cell remnants and nuclear material. Reactive oxygen species (ROS) released by neutrophils during oxidative burst are important for immune suppression and impairment of ROS production is seen in SLE. NETs mediate pathology in both SLE and APS via several mechanisms, including exposure of autoantigens, priming of T-cells and activation of autoreactive B-cells. NETs are also involved in cardiovascular events by forming a pro-thrombotic scaffolding surface. Lastly, neutrophils communicate with other cells by producing cytokines, such as Interferon (IFN) -α, and via direct cell-cell contact. Physiological neutrophil effector functions are necessary to prevent autoimmunity, but in SLE and APS these are altered.

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Section: Neutrophils and Their Effector Functions In Sle And Apsmentioning

confidence: 99%

Section: Neutrophils and Their Effector Functions In Sle And Apsmentioning

confidence: 99%

Neutrophils—Important Communicators in Systemic Lupus Erythematosus and Antiphospholipid Syndrome

et al. 2019

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“…Furthermore, neutrophils from APS patients were shown to display enhanced spontaneous NET release [134,142]. NET response might be mediated through activation of TLR4 [100,142], together with reactive oxygen species (ROS) [100,142,143]. Remarkably, IgG purified from APS patients induced NET release from healthy neutrophils [142].…”

Section: Antiphospholipid Syndrome (Aps)mentioning

confidence: 99%

“…An increase in NET release in response to autoantibodies could be explained by the presence of β2-GP1 on the surface of neutrophils [142]. Several studies observed anti-β2-GP1 to induce NET formation in healthy neutrophils [100,142,143]. Evidences suggest that NETs may directly mediate APS pathology by featuring as a scaffold for platelets to aggregate [144], possibly by presenting a tissue factor [53,100].…”

Section: Antiphospholipid Syndrome (Aps)mentioning

confidence: 99%

Neutrophil Extracellular Traps (NETs) Take the Central Stage in Driving Autoimmune Responses

Fousert

Toes

Desai

2020

Cells

182

128

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Following fifteen years of research, neutrophil extracellular traps (NETs) are widely reported in a large range of inflammatory infectious and non-infectious diseases. Cumulating evidences from in vitro, in vivo and clinical diagnostics suggest that NETs may play a crucial role in inflammation and autoimmunity in a variety of autoimmune diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV). Most likely, NETs contribute to breaking self-tolerance in autoimmune diseases in several ways. During this review, we discuss the current knowledge on how NETs could drive autoimmune responses. NETs can break self-tolerance by being a source of autoantigens for autoantibodies found in autoimmune diseases, such as anti-citrullinated protein antibodies (ACPAs) in RA, anti-dsDNA in SLE and anti-myeloperoxidase and anti-protein 3 in AAV. Moreover, NET components could accelerate the inflammatory response by mediating complement activation, acting as danger-associated molecular patterns (DAMPs) and inflammasome activators, for example. NETs also can activate other immune cells, such as B cells, antigen-presenting cells and T cells. Additionally, impaired clearance of NETs in autoimmune diseases prolongs the presence of active NETs and their components and, in this way, accelerate immune responses. NETs have not only been implicated as drivers of inflammation, but also are linked to resolution of inflammation. Therefore, NETs may be central regulators of inflammation and autoimmunity, serve as biomarkers, as well as promising targets for future therapeutics of inflammatory autoimmune diseases.

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