The role of microparticles in the pathogenesis of rheumatic diseases

Beyer, Christian; Pisetsky, David S.

doi:10.1038/nrrheum.2009.229

Cited by 233 publications

(224 citation statements)

References 92 publications

Supporting

Mentioning

212

Contrasting

Unclassified

Order By: Relevance

“…Consequently, the proportion of circulating cell-derived MPs with surface-bound IgG was significantly increased in the SLE group (median [5th-95th percentile] 3.5% [0. [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22].3%] in the SLE patient group versus 0.4% [0.02-4.3%] in the healthy control group; P Ͻ 0.0001).…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Increased IgG on cell‐derived plasma microparticles in systemic lupus erythematosus is associated with autoantibodies and complement activation

Nielsen

Østergaard

Stener

et al. 2012

Arthritis & Rheumatism

154

146

View full text Add to dashboard Cite

Objective. To quantify immunoglobulin and C1q on circulating cell-derived microparticles (MPs) in patients with systemic lupus erythematosus (SLE) and to determine whether immunoglobulin and C1q levels are correlated with clinical and serologic parameters.Methods. Sixty-eight clinically well-characterized SLE patients, 38 healthy controls, 6 patients with systemic sclerosis (SSc), and 6 patients with rheumatoid arthritis (RA) were included. The numbers of annexin V-binding MPs displaying IgG, IgM, or C1q were enumerated by flow cytometry. MP protein levels were determined by mass spectrometry in clinically defined subsets of SLE patients and controls. The MP IgG load was determined by flow cytometric analysis of all samples from SLE patients and healthy controls.Results. SLE patients had significantly increased total and relative numbers of IgG-positive MPs (P ‫؍‬ 0.0004), with a much higher average IgG load per MP (P < 0.0001) than healthy controls. Quantitative mass spectrometry of purified MPs verified significantly increased IgG, IgM, and C1q levels in SLE patients. In RA and SSc patients, the average IgG load per MP was significantly lower than in SLE patients (P ‫؍‬ 0.006 and P ‫؍‬ 0.05, respectively). Also, the IgM load and C1q load per MP were significantly higher in SLE patients than in the control groups (P < 0.05), except for IgM in the RA group. IgG-positive MPs were significantly associated with the presence of anti-double-stranded DNA, anti-extractable nuclear antigen, and antihistone antibodies, with total IgG, and with decreased leukocyte counts. Average IgG load per MP was associated with lower concentrations of MPs, the presence of anti-C1q antibodies, and complement consumption. Systemic lupus erythematosus (SLE) is an autoimmune disease with a wide range of clinical manifestations (1). One of the serologic hallmarks of SLE is the presence of circulating, high-affinity autoantibodies against nuclear constituents (2). These autoantibodies may form circulating proinflammatory immune complexes (ICs) that directly trigger plasmacytoid dendritic cells (PDCs) and the complement system, e.g., in the kidneys (3). Also, IC and autoantibody activation of SLE neutrophils prone to NETosis, i.e., specialized neutrophil cell death, contributes to the sustained PDC activation that is typical of SLE (4,5). The etiology of antinuclear autoimmunity in SLE remains unclear, but persistent, poorly cleared circulating cellular remnants, including microparticles (MPs) and neutrophil extracellular traps, are likely sources of immunogenic autoantigens (6-9). Conclusion. Our findings indicate that circulating cell-derived MPs in SLE patients

show abstract

Section: Resultsmentioning

confidence: 99%

“…Circulating cell-derived MPs are heterogeneous submicrometer-sized vesicles that are shed from the surface of cells, constitutively or during activation or apoptosis (10,11). Apoptotic MPs formed in vitro contain nuclear autoantigens that are accessible to autoantibodies (6,12,13).…”

mentioning

confidence: 99%

Increased IgG on cell‐derived plasma microparticles in systemic lupus erythematosus is associated with autoantibodies and complement activation

Nielsen

Østergaard

Stener

et al. 2012

Arthritis & Rheumatism

154

146

View full text Add to dashboard Cite

show abstract

“…Microparticles (also called extracellular vesicles) are submicrometer‐sized membrane vesicles (0.05–1 μm diameter) that are actively shed from cells in response to activation, injury, and apoptosis 15, 16. A number of recent studies have shown that diseases of the vasculature and kidneys, including CKD, are associated with increased numbers of circulating endothelial microparticles 17, 18, 19, 20, 21, 22.…”

Section: Introductionmentioning

confidence: 99%

Endothelial Microparticles and Systemic Complement Activation in Patients With Chronic Kidney Disease

Jalal

Renner

Laskowski

et al. 2018

JAHA

View full text Add to dashboard Cite

BackgroundEndothelial microparticles are associated with chronic kidney disease (CKD) and complement activation. We hypothesized that the complement pathway is activated in patients with CKD via endothelial microparticles and that complement activation correlates with endothelial dysfunction in CKD.Methods and ResultsWe analyzed complement data of 30 healthy subjects, 30 patients with stage III/IV CKD, and 30 renal transplant recipients with stage III/IV CKD, evaluating the potential correlation of complement fragments with brachial artery flow–mediated dilation, Chronic Kidney Disease Epidemiology Collaboration glomerular filtration rate, and urinary albumin/creatinine ratio. Endothelial microparticles were characterized via proteomic analysis and compared between study groups. Complement fragment Ba was significantly increased in CKD and post–kidney transplant CKD. Plasma Ba levels correlated significantly with lower brachial artery flow–mediated dilation, lower Chronic Kidney Disease Epidemiology Collaboration glomerular filtration rate, and higher urinary albumin/creatinine ratio. Factor D levels were significantly higher in the plasma microparticles of patients with CKD versus healthy controls. Plasma microparticles isolated from patients with CKD and containing factor D activated the alternative pathway in vitro.ConclusionThe alternative complement pathway is activated in CKD and correlates with endothelial dysfunction and markers of CKD. Future studies are needed to evaluate whether endothelial microparticles with increased factor D play a pathologic role in CKD‐associated vascular disease.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02230202.

show abstract

“…Because of their abundance, platelet-derived MPs (PMPs) received the highest attention during the past few years. Elevated PMP counts are characteristic for nearly all autoimmune disorders [4,5], and also for several cardiovascular and metabolic diseases [1]. EVs not only contain proteins but also RNA molecules [1].…”

mentioning

confidence: 99%

Improved circulating microparticle analysis in acid-citrate dextrose (ACD) anticoagulant tube

György

Pálóczi

Kovacs

et al. 2014

Thrombosis Research

108

View full text Add to dashboard Cite

Introduction: Recently extracellular vesicles (exosomes, microparticles also referred to as microvesicles and apoptotic bodies) have attracted substantial interest as potential biomarkers and therapeutic vehicles. However, analysis of microparticles in biological fluids is confounded by many factors such as the activation of cells in the blood collection tube that leads to in vitro vesiculation. In this study we aimed at identifying an anticoagulant that prevents in vitro vesiculation in blood plasma samples. Materials and Methods: We compared the levels of platelet microparticles and non-platelet-derived microparticles in platelet-free plasma samples of healthy donors. Platelet-free plasma samples were isolated using different anticoagulant tubes, and were analyzed by flow cytometry and Zymuphen assay. The extent of in vitro vesiculation was compared in citrate and acid-citrate-dextrose (ACD) tubes. Results: Agitation and storage of blood samples at 37°C for 1 hour induced a strong release of both platelet microparticles and non-platelet-derived microparticles. Strikingly, in vitro vesiculation related to blood sample handling and storage was prevented in samples in ACD tubes. Importantly, microparticle levels elevated in vivo remained detectable in ACD tubes. Conclusions: We propose the general use of the ACD tube instead of other conventional anticoagulant tubes for the assessment of plasma microparticles since it gives a more realistic picture of the in vivo levels of circulating microparticles and does not interfere with downstream protein or RNA analyses.© 2013 Elsevier Ltd. All rights reserved. IntroductionExtracellular vesicles (EVs) are membrane surrounded structures of various sizes (30-5000 nm) that have received significant attention recently [1]. EVs may be classified on the basis of their biogenesis, diameter and membrane markers. The two best characterized types of EVs include exosomes of endosomal origin and plasma membrane-derived microparticles (MPs) (recently often referred to also as microvesicles or ectosomes in the literature) [1]. EVs are present in all biological fluids including blood plasma, synovial fluid, cerebrospinal fluid, urine, tears and breast milk [1]. MPs are in between 100 and 1000 nm in diameter, and they are also detectable by flow cytometry [2,3]. Thus, MP profiles are easily analyzed in the routine clinical laboratory practice, and represent novel biomarkers of various diseases. In circulation, most MPs are derived from platelets, red blood cells, endothelial cells and leukocytes. Because of their abundance, platelet-derived MPs (PMPs) received the highest attention during the past few years. Elevated PMP counts are characteristic for nearly all autoimmune disorders [4,5], and also for several cardiovascular and metabolic diseases [1]. EVs not only contain proteins but also RNA molecules [1]. Extracellular RNA (exRNA) in blood plasma is encapsulated in EVs, or bound to either proteins or HDL molecules [6]. exRNAs, particularly miRNAs, are specific and sensitive biomarkers...

show abstract

The role of microparticles in the pathogenesis of rheumatic diseases

Cited by 233 publications

References 92 publications

Increased IgG on cell‐derived plasma microparticles in systemic lupus erythematosus is associated with autoantibodies and complement activation

Increased IgG on cell‐derived plasma microparticles in systemic lupus erythematosus is associated with autoantibodies and complement activation

Endothelial Microparticles and Systemic Complement Activation in Patients With Chronic Kidney Disease

Improved circulating microparticle analysis in acid-citrate dextrose (ACD) anticoagulant tube

Contact Info

Product

Resources

About