Objective. To quantify immunoglobulin and C1q on circulating cell-derived microparticles (MPs) in patients with systemic lupus erythematosus (SLE) and to determine whether immunoglobulin and C1q levels are correlated with clinical and serologic parameters.Methods. Sixty-eight clinically well-characterized SLE patients, 38 healthy controls, 6 patients with systemic sclerosis (SSc), and 6 patients with rheumatoid arthritis (RA) were included. The numbers of annexin V-binding MPs displaying IgG, IgM, or C1q were enumerated by flow cytometry. MP protein levels were determined by mass spectrometry in clinically defined subsets of SLE patients and controls. The MP IgG load was determined by flow cytometric analysis of all samples from SLE patients and healthy controls.Results. SLE patients had significantly increased total and relative numbers of IgG-positive MPs (P ‫؍‬ 0.0004), with a much higher average IgG load per MP (P < 0.0001) than healthy controls. Quantitative mass spectrometry of purified MPs verified significantly increased IgG, IgM, and C1q levels in SLE patients. In RA and SSc patients, the average IgG load per MP was significantly lower than in SLE patients (P ‫؍‬ 0.006 and P ‫؍‬ 0.05, respectively). Also, the IgM load and C1q load per MP were significantly higher in SLE patients than in the control groups (P < 0.05), except for IgM in the RA group. IgG-positive MPs were significantly associated with the presence of anti-double-stranded DNA, anti-extractable nuclear antigen, and antihistone antibodies, with total IgG, and with decreased leukocyte counts. Average IgG load per MP was associated with lower concentrations of MPs, the presence of anti-C1q antibodies, and complement consumption. Systemic lupus erythematosus (SLE) is an autoimmune disease with a wide range of clinical manifestations (1). One of the serologic hallmarks of SLE is the presence of circulating, high-affinity autoantibodies against nuclear constituents (2). These autoantibodies may form circulating proinflammatory immune complexes (ICs) that directly trigger plasmacytoid dendritic cells (PDCs) and the complement system, e.g., in the kidneys (3). Also, IC and autoantibody activation of SLE neutrophils prone to NETosis, i.e., specialized neutrophil cell death, contributes to the sustained PDC activation that is typical of SLE (4,5). The etiology of antinuclear autoimmunity in SLE remains unclear, but persistent, poorly cleared circulating cellular remnants, including microparticles (MPs) and neutrophil extracellular traps, are likely sources of immunogenic autoantigens (6-9). Conclusion. Our findings indicate that circulating cell-derived MPs in SLE patients