Fariborz Mobarrez1, Enrico Fuzzi2, Iva Gunnarsson2, Anders Larsson3, Susanna Eketjäll4, David S Pisetsky5, Elisabet Svenungsson2. 1. Unit of Rheumatology, Department of Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, SE-171 76, Stockholm, Sweden; Department of Medical Sciences, Uppsala University, Akademiska Hospital, SE-751 85, Uppsala, Sweden. Electronic address: fariborz.mobarrez@medsci.uu.se. 2. Unit of Rheumatology, Department of Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, SE-171 76, Stockholm, Sweden. 3. Department of Medical Sciences, Uppsala University, Akademiska Hospital, SE-751 85, Uppsala, Sweden. 4. Cardiovascular, Renal and Metabolism, IMED Biotech Unit, AstraZeneca, Integrated Cardio Metabolic Centre, Karolinska Institutet, Huddinge, Sweden. 5. Department of Medicine, Duke University Medical Center; Medical Research Service, Durham VA Hospital Sweden.
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.
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 SLEpatients 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 SLEpatients compared to 280 controls. In 47 SLEpatients, 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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