| 1. |
- Woolf, Anthony D., et al.
(author)
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Clinical advances – from bench to bedside
- 2020
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In: Best Practice and Research: Clinical Rheumatology. - : Elsevier BV. - 1521-6942. ; 34:5
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Research review (peer-reviewed)
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| 2. |
- Mobarrez, Fariborz, et al.
(author)
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Microparticles in the blood of patients with SLE : Size, content of mitochondria and role in circulating immune complexes
- 2019
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In: Journal of Autoimmunity. - : Elsevier BV. - 0896-8411 .- 1095-9157. ; 102, s. 142-149
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Microparticles (MPs) are small extracellular vesicles released from apoptotic or activated cells through a blebbing process. MPs express surface molecules from their parental cells and they bind IgG to form circulating immune complexes (MP-ICs) in patients with systemic lupus erythematosus (SLE). Through investigation of MP size, IgG expression, content of nucleic acids and mitochondrial molecules, we hypothesized that unrecognized particle populations can be identified in SLE.METHODS: We investigated 327 well-characterized SLE patients and 304 controls divided into two sets (280/280 and 47/24). We measured MPs by flow cytometry using a gating strategy to encompass small (0.2-0.7 μm) and large (0.7-3.0 μm) MPs. Nucleic acids were labeled with SYTO 13 and mitochondria with MitoTracker. Expression of mitochondria markers TOM-20 and Hexokinase 1 and the presence of IgG was investigated.RESULTS: MPs staining with SYTO 13 were more frequent in 280 SLE patients compared to 280 controls. In 47 SLE patients, levels of large MPs were elevated compared to 24 controls. The majority of large MPs contained mitochondria (mitoMPs). The number of mitoMPs associated positively with high disease activity, anti-dsDNA antibodies and pro-inflammatory cytokines. Patients with active lupus nephritis had higher levels of mitoMPs and IgG-positive mitoMPs.CONCLUSION: Blood of patients with SLE contain a previously unrecognized population of circulating large MPs with bound IgG and mitochondrial proteins. Levels of these particles are related to several measures of active SLE, suggesting that these structures may have a role in disease pathogenesis.
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| 3. |
- Mobarrez, Fariborz, et al.
(author)
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Microparticles in the blood of patients with systemic lupus erythematosus (SLE) : phenotypic characterization and clinical associations
- 2016
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Journal article (peer-reviewed)abstract
- 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.
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| 4. |
- Mobarrez, Fariborz, et al.
(author)
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The Effects of Smoking on Levels of Endothelial Progenitor Cells and Microparticles in the Blood of Healthy Volunteers
- 2014
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In: PLOS ONE. - San Francisco : Public Library of Science. - 1932-6203. ; 9:2, s. e90314-
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Journal article (peer-reviewed)abstract
- Background: Cigarette smoking, both active and passive, is one of the leading causes of morbidity and mortality in cardiovascular disease. To assess the impact of brief smoking on the vasculature, we determined levels of circulating endothelial progenitor cells (EPCs) and circulating microparticles (MPs) following the smoking of one cigarette by young, healthy intermittent smokers. Materials and Methods: 12 healthy volunteers were randomized to either smoking or not smoking in a crossover fashion. Blood sampling was performed at baseline, 1, 4 and 24 hours following smoking/not smoking. The numbers of EPCs and MPs were determined by flow cytometry. MPs were measured from platelets, leukocytes and endothelial cells. Moreover, MPs were also labelled with anti-HMGB1 and SYTO 13 to assess the content of nuclear molecules. Results: Active smoking of one cigarette caused an immediate and significant increase in the numbers of circulating EPCs and MPs of platelet-, endothelial-and leukocyte origin. Levels of MPs containing nuclear molecules were increased, of which the majority were positive for CD41 and CD45 (platelet-and leukocyte origin). CD144 (VE-cadherin) or HMGB1 release did not significantly change during active smoking. Conclusion: Brief active smoking of one cigarette generated an acute release of EPC and MPs, of which the latter contained nuclear matter. Together, these results demonstrate acute effects of cigarette smoke on endothelial, platelet and leukocyte function as well as injury to the vascular wall.
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| 5. |
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| 6. |
- Pisetsky, David S., et al.
(author)
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The binding of SLE autoantibodies to mitochondria
- 2020
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In: Clinical Immunology. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 1521-6616 .- 1521-7035. ; 212
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Journal article (peer-reviewed)abstract
- Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by immune complexes. Because these complexes contain mitochondrial components, we assessed the presence of antibodies to whole mitochondria (wMITO) using an ELISA in which mitochondria from mouse liver are bound to microtiter plates pre-coated with poly-L-lysine. Studies with this ELISA demonstrated that SLE plasmas contain abundant anti-wMITO activity. While digestion with DNase 1 did not affect anti-wMITO activity, adsorption of plasma on DNA affinity columns could reduce binding activity. Assay for anti-mitochondrial antibodies (AMA) by immunofluorescence and an ELISA with the M2 antigen (2-oxo-acid dehydrogenase protein complex) showed a low frequency of positivity, indicating that AMA and anti-wMITO are distinct specificities. In the study of 204 patients with SLE, the levels of anti-wMITO were higher in active SLE and correlated with levels of anti-DNA. These findings suggest that anti-wMITO can form immune complexes with mitochondria which may drive pathogenesis.
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