Endothelial and platelet microparticles in patients with antiphospholipid antibodies

Breen, Karen; Sanchez, Katy; Kirkman, Nicola; Seed, Paul; Parmar, Kiran; Moore, Gary; Hunt, Beverley J.

doi:10.1016/j.thromres.2014.11.027

Cited by 47 publications

(39 citation statements)

References 49 publications

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“…The increased numbers of MPs observed in SLE patients most likely result from defective clearance together with enhanced cell activation and apoptosis, which are all mechanisms related to underlying SLE pathogenesis, as discussed elsewhere . Moreover, elevated numbers of endothelial and platelet MPs have previously also been demonstrated in APS patients . In addition to elevated concentrations of MPs, SLE patients have high concentrations of mpICs.…”

Section: Discussionmentioning

confidence: 99%

Altered β2‐glycoprotein I expression on microparticles in the presence of antiphospholipid antibodies

Mobarrez

Gunnarsson

Svenungsson

2017

Journal of Thrombosis and Haemostasis

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Essentials β2 glycoprotein-I (β GPI) is a scavenger molecule that binds to microparticles (MPs). β GPI expression on MPs was measured in systemic lupus erythematosus (SLE) patients and controls. β GPI positive MPs is depressed among SLE patients positive for antiphospholipid antibodies. Complex formation between β GPI on MPs and patients own anti-β GPI may disturb MP clearance. Click to hear an ISTH Academy presentation on antiphospholipid antibody syndrome by Drs de Laat and Bertolaccini SUMMARY: Background Antiphospholipid antibodies (aPLs) together with thrombosis and/or pregnancy morbidities characterize the antiphospholipid syndrome. β -Glycoprotein I (β GPI), the most important antigen for aPLs, is a scavenger molecule that specifically binds to phosphatidylserine (PS) expressed on microparticles (MPs). Objectives To evaluate β GPI-expressing MPs in patients with systemic lupus erythematosus (SLE) stratified for aPL status, and in healthy controls. Patients/Methods We investigated 18 aPL/anti-β GPI-positive and 22 aPL-negative patients from a large SLE cohort and 19 healthy controls. β GPI-positive MPs and IgG-positive MPs were detected by flow cytometry. We measured plasma levels of β GPI, and performed in vitro experiments to investigate the binding properties of β GPI on MPs. Results SLE patients had more MPs and IgG-positive MPs than controls. We observed fewer β GPI-positive MPs in aPL/anti-β GPI-positive patients than in aPL/anti-β GPI-negative patients and controls (approximately two-fold). β GPI levels in plasma did not differ with aPL/anti-β GPI status in patients; however, controls had slightly higher levels of β GPI than aPL/anti-β GPI-positive patients. In vitro experiments revealed that β GPI preferentially binds to PS-positive MPs. Conclusions Despite abundant total MPs and MPs in immune complexes, β GPI-positive MPs were depleted in SLE patients, and the levels were especially low in aPL/anti-β GPI-positive patients. We suggest that anti-β GPI antibodies bind to β GPI-PS complexes expressed on MPs. Consequent loss of β GPI-PS expression on MPs may impair scavenging and contribute to the accumulation of circulating PS-negative MPs, a possible source of autoantigens. Autoantibodies delaying MP clearance may thus constitute an important mechanism underlying autoimmunity.

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Section: Discussionmentioning

confidence: 99%

Altered β2‐glycoprotein I expression on microparticles in the presence of antiphospholipid antibodies

Mobarrez

Gunnarsson

Svenungsson

2017

Journal of Thrombosis and Haemostasis

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“…A number of studies have compared the levels of MPs in the blood of patients with primary APS, SLE patients with secondary APS, SLE patients with or without antiphospholipid antibodies (aPL) in the absence of secondary APS, and healthy individuals with or without aPL in the absence of thrombotic events. In general, these studies have reported elevated numbers of EMPs in patients with APS, lending credence to links of EMPs with thrombotic events and pregnancy complications [57][58][59]. However, the precise contribution to thrombosis remains unclear.…”

Section: Anti-phospholipid Syndromementioning

confidence: 84%

Endothelial microparticles: Pathogenic or passive players in endothelial dysfunction in autoimmune rheumatic diseases?

McCarthy

Wilkinson

Parker

et al. 2016

Vascular Pharmacology

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Autoimmune rheumatic diseases are characterised by systemic inflammation and complex immunopathology, with an increased risk of cardiovascular disease, initiated by endothelial dysfunction in a chronic inflammatory environment. Endothelial microparticles (EMPs) are released into the circulation from activated endothelial cells and may therefore, reflect disease severity, vascular and endothelial dysfunction, that could influence disease pathogenesis via autocrine/paracrine signalling. The exact function of EMPs in rheumatic disease remains unknown, and this has initiated research to elucidate EMP composition and function, which may be determined by the mode of endothelial activation and the micro environment. To date, EMPs are thought to play a role in angiogenesis, thrombosis and inflammation by transferring specific proteins and microRNAs (miRs) to target cells. Here, we review the mechanisms underlying the generation and composition of EMPs and the clinical and experimental studies describing the involvement of EMPs in rheumatic diseases, since we have previously shown endothelial dysfunction and an elevated risk of cardiovascular disease are characteristics in systemic lupus erythematosus. We will also discuss the potential of EMPs as future biomarkers of cardiovascular risk in these diseases.

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“…The role of thrombocytes in the pathogenesis of APS is supported by the fact that circulating platelet-and endothelial-derived microparticle level are elevated in patients with primary APS [31].…”

Section: Role Of Platelets In Apsmentioning

confidence: 99%

Antiphospholipid Syndrome and Thrombocytopenia

Gadó¹,

Domján²

2018

Thrombocytopenia

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Antiphospholipid syndrome is characterised by arterial and venous thromboembolic events and pregnancy morbidity (mainly, recurrent foetal losses), in the presence of antiphospholipid antibodies. Diagnosis is based on the presence of at least one laboratory and at least one clinical manifestation of antiphospholipid syndrome. There are also socalled "non-criteria" clinical features, and thrombocytopenia is one of the most important among them. Thrombocytopenia has been reported with a prevalence between 30 and 46% among patients with antiphospholipid syndrome. The pathogenesis of thrombocytopenia related to antiphospholipid antibodies is not absolutely clear. Binding of antiphospholipid antibodies to platelets and the promotion of platelet activation and aggregation thus thrombus formation must be an important mechanism as well as the immune-mediated clearance of platelets. Thrombocytopenia in antiphospholipid syndrome is usually mild and does not require clinical intervention. The presence of thrombocytopenia in patients with antiphospholipid syndrome is typically associated not with haemorrhagic complications, rather it can trigger thrombotic events. Other causes of thrombocytopenia, such as TTP, SLE, MDS, and ITP should be excluded. As thrombocytopenia is usually mild and it predicts later thrombosis, patients may be given platelet aggregation inhibitors and/ or anticoagulant therapy. Anti-thrombotic treatment should be stopped only in case of severe thrombocytopenia.

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Endothelial and platelet microparticles in patients with antiphospholipid antibodies

Cited by 47 publications

References 49 publications

Altered β2‐glycoprotein I expression on microparticles in the presence of antiphospholipid antibodies

Altered β2‐glycoprotein I expression on microparticles in the presence of antiphospholipid antibodies

Endothelial microparticles: Pathogenic or passive players in endothelial dysfunction in autoimmune rheumatic diseases?

Antiphospholipid Syndrome and Thrombocytopenia

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