Background/Purpose: Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by immune complexes, especially those with nuclear molecules bound by antinuclear antibodies. Although the source of these antigens is not fully known, increased apoptosis and defective clearance of dead cells have been proposed. During apoptosis and cell activation, microparticles (MPs) are released extracellularly. MPs are small membrane-bound particles that can contain molecules arising from both the nucleus and cytoplasm. Moreover, these MPs are often covered with immunoglobulins, thus forming MP-immune complexes (mpICs).

Methods: Plasma samples from 47 patients with SLE (4³ of 1982 ACR criteria) and 24 healthy controls were investigated. MPs and mpICs were analyzed by flow cytometry and defined by size; MPs (< 7.0 µm) or mpICs (> 7.0 µm). Samples were labeled with MitoTracker deep red FM to investigate mitochondrial content. Flow cytometry was also used to assess outer mitochondria markers by staining with anti-Tom-20 and anti-hexokinase I. The presence of IgG was evaluated with an anti-IgG reagent.

Results: Levels of both MPs and mpICs in SLE patients were significantly elevated compared to controls (Fig 1A). Although MP concentrations were higher than those of mpICs, mpICs contained more mitochondria compared to MPs (Fig 1B). mpICs also displayed IgG and exposed the outer mitochondria markers. The number of mpICs containing mitochondria correlated strongly to the presence of anti-dsDNA antibodies (Fig 2) as well as to levels of TNF-_ (r² 0.2, p<0.05), IL-6 (r² 0.23, p<0.01) and IL-7 (r² 0.24, p<0.01). Moreover, compared to patients with inactive renal disease, patients with active renal disease had significantly higher levels of IgG-coated mpICs containing mitochondria (p<0.01). Patients with SLAM above 6, had significantly higher numbers of mpICs containing mitochondria and exposing outermitochondria markers Tom-20 and hexokinase I (p<0.05).

Conclusion: MPs and mpICs are significantly more abundant in the blood of SLE patients compared to controls. Importantly, the majority of the mitochondria were present in the larger mpIC sup-population. Moreover, mpICs that contain mitochondria also display outer mitochondria markers, with levels correlating with levels of anti-dsDNA antibodies, disease activity and pro-inflammatory cytokines. mpICs may therefore contribute to SLE pathogenesis, with mitochondria representing a source of cell antigens that can trigger innate and adaptive immune responses as well as deposit in the tissue.