CD40L expression in plasma of volunteers following LPS administration: A comparison between assay of CD40L on platelet microvesicles and soluble CD40L

Vikerfors

Gustafsson

et al. 2016

Sci Rep

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Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by circulating autoantibodies and the formation of immune complexes. In these responses, the selecting self-antigens likely derive from the remains of dead and dying cells, as well as from disturbances in clearance. During cell death/activation, microparticles (MPs) can be released to the circulation. Previous MP studies in SLE have been limited in size and differ regarding numbers and phenotypes. Therefore, to characterize MPs more completely, we investigated 280 SLE patients and 280 individually matched controls. MPs were measured with flow cytometry and phenotyped according to phosphatidylserine expression (PS+/PS−), cellular origin and inflammatory markers. MPs, regardless of phenotype, are 2–10 times more abundant in SLE blood compared to controls. PS− MPs predominated in SLE, but not in controls (66% vs. 42%). Selectively in SLE, PS− MPs were more numerous in females and smokers. MP numbers decreased with declining renal function, but no clear association with disease activity was observed. The striking abundance of MPs, especially PS− MPs, suggests a generalized disturbance in SLE. MPs may be regarded as “liquid biopsies” to assess the production and clearance of dead, dying and activated cells, i.e. pivotal events for SLE pathogenesis.

Section: Resultsmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Microparticles in the blood of patients with systemic lupus erythematosus (SLE): phenotypic characterization and clinical associations

Vikerfors

Gustafsson

et al. 2016

Sci Rep

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“…The discrepancy between the two assays could be related to sensitivity. We have previously shown that measurement of soluble proteins on MPs yields higher sensitivity, as the flow cytometer only measures proteins bound to particles, whereas ELISA measures both bound and soluble proteins [36]. A previous study by Vlachoyiannopoulos et al showed that b 2 GPI levels in patients with APS were higher than those in SLE patients negative for aCLs [37].…”

Section: Discussionmentioning

confidence: 98%

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

Journal of Thrombosis and Haemostasis

Gunnarsson

Svenungsson

2017

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.

“…Our results, together with the findings by Yamamoto et al ., raise for the possibility that sCD40 ligand may be used as a biomarker of disease activity. In this regard, we have recently provided data suggesting measurements of CD40 ligand on platelet‐MVs may be a more sensitive marker of inflammation than sCD40 ligand . P‐selectin is mainly expressed on activated platelets and plays a role in the recruitment of leucocytes by binding to its ligand, P‐selectin glycoprotein ligand‐1 .…”

Section: Discussionmentioning

confidence: 99%

The expression of microvesicles in the blood of patients withGraves' disease and its relationship to treatment

Abraham-Nordling

Aguilera-Gatica

et al. 2015

Clinical Endocrinology

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