Journal
JOURNAL OF AUTOIMMUNITY
Volume 102, Issue -, Pages 142-149Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jaut.2019.05.003
Keywords
Systemic lupus erythematosus; Microparticles; Microvesicles; Mitochondria
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Funding
- Swedish Research Council
- Swedish Heart-Lung Foundation
- ALF funding from Stockholm County Council
- Karolinska Institutet
- Swedish Rheumatism Association
- King Gustaf V 80th Birthday Fund
- Swedish Society of Medicine
- Foundation in memory of Clas Groschinsky
- Ingegerd Johansson Donation Foundation
- Karolinska Institutet Foundation
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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 mitochondria] 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 mu m) and large (0.7-3.0 mu m) 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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