Mechanisms of Action of the Antiphospholipid Antibodies

Chighizola, Cecilia Beatrice; Raschi, Elena; Borghi, Maria Orietta; Meroni, Pier Luigi

doi:10.1016/b978-0-444-63655-3.00003-x

Cited by 4 publications

(9 citation statements)

References 45 publications

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“…Vasculopathy)which can make one of the earliest symptoms of the disease(, Raynaud’s Phenomenon (happen as well as digital ulcers), pulmonary arterial hypertension, and telangiectasia (Rozier et al 2018 ; Velier et al 2019 ; Desbois and Cacoub 2016 ) are associated with SSc. The main characteristic of the disease is the collagen accumulation in the skin and internal organs, especially the lungs, but the involvement of the heart and digestive system is also reported (Maria et al 2016a ; Rozier et al 2018 ; Velier et al 2019 ; Chighizola et al 2011 ; Okamura et al 2020 ). As mentioned, there are three main axes which cause the symptoms: autoimmunity, vascular abnormality, and fibrosis (Asano 2018 ; Maria et al 2016a ; Rozier et al 2018 ; Okamura et al 2020 ).…”

Section: A Review Of Scleroderma Symptoms and Pathophysiologymentioning

confidence: 99%

Mesenchymal stem cell as a novel approach to systemic sclerosis; current status and future perspectives

et al. 2020

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Systemic sclerosis is a rare chronic autoimmune disease with extensive microvascular injury, damage of endothelial cells, activation of immune responses, and progression of tissue fibrosis in the skin and various internal organs. According to epidemiological data, women’s populations are more susceptible to systemic sclerosis than men. Until now, various therapeutic options are employed to manage the symptoms of the disease. Since stem cell-based treatments have developed as a novel approach to rescue from several autoimmune diseases, it seems that stem cells, especially mesenchymal stem cells as a powerful regenerative tool can also be advantageous for systemic sclerosis treatment via their remarkable properties including immunomodulatory and anti-fibrotic effects. Accordingly, we discuss the contemporary status and future perspectives of mesenchymal stem cell transplantation for systemic sclerosis.

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Section: A Review Of Scleroderma Symptoms and Pathophysiologymentioning

confidence: 99%

Mesenchymal stem cell as a novel approach to systemic sclerosis; current status and future perspectives

et al. 2020

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“…Thus, a co-receptor is required to trigger signaling cascade: toll-like receptor (TLR) 2 and TLR4, heparan sulfate, and apolipoprotein E receptor 2′ (ApoER2′) have all been shown to bind β2GPI. 9 Upon engagement of β2GPI receptors on target cells, anti-β2GPI antibody binding results in the activation of intracellular mediators such as nuclear factor κB (NFκB), p38 mitogen-activated protein kinase (p38MAPK), phosphatidylinositol 3-kinase (PI3K), AKT, mammalian target of rapamycin (mTOR), NLRP3, and caspase-1 via the activation of endosomal NADPH-oxidase (NOX)-2. 9 PE.…”

Section: Antiphospholipid Antibodiesmentioning

confidence: 99%

“…aPL binding to monocytes results in the upregulation of tissue factor, one of the major initiators of the coagulation cascade. 9 Recently, neutrophils have been identified as an additional player in the pathogenesis of aPL-mediated vascular thrombosis. Indeed, sera and IgG from APS patients as well as human aPL monoclonals, especially those targeting β2GPI, stimulate the release from neutrophils of extracellular traps, structures consisting in decondensed chromatin assembled with nuclear proteins that can trigger the intrinsic coagulation cascade, inhibit anticoagulant factors, and activate platelets.…”

Section: Antiphospholipid Antibodiesmentioning

confidence: 99%

“…Furthermore, aPLs disrupt the crystallization on ECs of annexin A5, a potent anticoagulant that prevents the bioavailability of phospholipids for coagulation enzymes. 9 Activation of the complement cascade is an additional critical effector mechanism in aPL-associated thrombosis, amplifying aPL deleterious effects by stimulating the generation of potent proinflammatory mediators such as C3a, C5a, and the C5b-9 membrane attack complex (MAC). 34 The management of APS patients with VTE parallels the therapeutic approach reserved to the general population.…”

Section: Antiphospholipid Antibodiesmentioning

confidence: 99%

“…34 The pathogenic action of aPLs in the lungs might be facilitated by the pulmonary microbiota: indeed, microorganisms might activate TLRs, thus acting as a second hit. 9,105 Microvascular thrombosis and rupture of small pulmonary vessels have also been suggested as potential pathogenic mechanisms of DAH in APS. 102,106 With regard to treatment, the management of anticoagulation in APS patients with DAH is a matter of great debate.…”

Section: Diffuse Alveolar Hemorrhagementioning

confidence: 99%

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Lung Disease in Antiphospholipid Syndrome

Maioli

Calabrese

Capsoni

et al. 2019

Semin Respir Crit Care Med

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Antiphospholipid syndrome (APS) is an acquired prothrombotic condition characterized by vascular thrombosis and/or obstetric complications, in the persistent positivity of circulating antiphospholipid antibodies (aPLs). The clinical spectrum of manifestations associated with aPL positivity is progressively expanding, including the description of several lung manifestations. The most common pulmonary involvement related to aPL positivity is pulmonary embolism (PE), which has been reported to occur in 14.1% of APS patients during disease course. PE acknowledges a purely thrombotic etiology and thus might be accounted as a criterion for APS, making imperative to test aPL in young subjects with unprovoked PE. Pulmonary hypertension (PH) can manifest in APS patients, being the second most common lung complication of the syndrome, with a prevalence ranging between 1.8 and 3.5%. aPL-positive patients might present PH following a PE, might develop pulmonary arterial hypertension associated with connective tissue disease, or might present pulmonary venous hypertension due to Libman–Sacks endocarditis. Additional lung manifestations, such as diffuse alveolar hemorrhage, acute respiratory distress syndrome, and pulmonary fibrosis, are rarely described in APS patients; it is still not clear whether in these settings aPLs exert a pathogenic role or is a mere epiphenomenon. Hereby we discuss impact, clinical presentation, histopathologic findings, etiology, and treatment of each aPL-associated lung manifestation.

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The Pathophysiology of The Antiphospholipid Syndrome: A Perspective From The Blood Coagulation System

Arreola-Díaz

Majluf‐Cruz

Sánchez-Torres

et al. 2022

Clin Appl Thromb Hemost

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The antiphospholipid syndrome (APS), a systemic autoimmune disease characterized by a hypercoagulability associated to vascular thrombosis and/or obstetric morbidity, is caused by the presence of antiphospholipid antibodies such as lupus anticoagulant, anti-β-2-glycoprotein 1, and/or anticardiolipin antibodies. In the obstetrical APS, antiphospholipid antibodies induce the production of proinflammatory cytokines and tissue factor by placental tissues and recruited neutrophils. Moreover, antiphospholipid antibodies activate the complement system which, in turn, induces a positive feedback leading to recruitment of neutrophils as well as activation of the placenta. Activation of these cells triggers myometrial contractions and cervical ripening provoking the induction of labor. In thrombotic and obstetrical APS, antiphospholipid antibodies activate endothelial cells, platelets, and neutrophils and they may alter the multimeric pattern and concentration of von Willebrand factor, increase the concentration of thrombospondin 1, reduce the inactivation of factor XI by antithrombin, increase the activation of factor XII, and reduce the activity of tissue plasminogen activator with the subsequent production of plasmin. All these effects result in less permeable clots, denser, thinner, and with more branched fibrin fibers which are more difficult to lysate. As a consequence, thrombosis, the defining clinical criterion of APS, complicates the clinical course of the patient.

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Mechanisms of Action of the Antiphospholipid Antibodies

Cited by 4 publications

References 45 publications

Mesenchymal stem cell as a novel approach to systemic sclerosis; current status and future perspectives

Mesenchymal stem cell as a novel approach to systemic sclerosis; current status and future perspectives

Lung Disease in Antiphospholipid Syndrome

The Pathophysiology of The Antiphospholipid Syndrome: A Perspective From The Blood Coagulation System

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