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Microparticles in the blood of patients with SLE: Size, content of mitochondria and role in circulating immune complexes
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine. Karolinska Inst, Karolinska Univ Hosp, Dept Med, Unit Rheumatol, SE-17176 Stockholm, Sweden.
Unit of Rheumatology, Department of Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, SE-171 76, Stockholm, Sweden..
Unit of Rheumatology, Department of Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, SE-171 76, Stockholm, Sweden..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.ORCID iD: 0000-0003-3161-0402
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2019 (English)In: Journal of Autoimmunity, ISSN 0896-8411, E-ISSN 1095-9157, Vol. 102, p. 142-149Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2019. Vol. 102, p. 142-149
Keywords [en]
Microparticles, Microvesicles, Mitochondria, Systemic lupus erythematosus
National Category
Rheumatology and Autoimmunity
Identifiers
URN: urn:nbn:se:uu:diva-385064DOI: 10.1016/j.jaut.2019.05.003ISI: 000479024700012PubMedID: 31103269OAI: oai:DiVA.org:uu-385064DiVA, id: diva2:1322482
Funder
Swedish Research CouncilSwedish Heart Lung FoundationThe Karolinska Institutet's Research FoundationSwedish Rheumatism AssociationKing Gustaf V Jubilee FundSwedish Society of MedicineAvailable from: 2019-06-10 Created: 2019-06-10 Last updated: 2019-09-26Bibliographically approved

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Mobarrez, FariborzLarsson, Anders

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