Microparticles (MPs) are vesicles derived from the plasma membrane of different cells, are considered a source of circulating autoantigens, and can form immune complexes (MPs-ICs). The number of MPs and MPs-ICs increases in patients with systemic lupus erythematosus (SLE). MPs activate myeloid cells by inducing IL-6 and TNF-α in both SLE and other diseases. Therefore, we propose that the recognition of MPs-ICs by monocytes rather that MPs may define their phenotype and contribute to the inflammatory process in patients with SLE. Thus, the aims of this study were to evaluate the association among circulating MPs-ICs from different cell sources, alterations observed in monocyte subsets, and disease activity in patients with SLE and to establish whether monocytes bind and respond to MPs-ICs in vitro. Circulating MPs and monocyte subsets were characterized in 60 patients with SLE and 60 healthy controls (HCs) using multiparametric flow cytometry. Patients had higher MP counts and frequencies of MPs-CD41a + (platelet-derived) compared with HCs, regardless of disease activity. MPs from patients with SLE were C1q + and formed ICs with IgM and IgG. MPs-IgG + were positively correlated with active SLE (aSLE), whereas MPs-IgM + were negatively correlated. Most of the circulating total ICs-IgG + were located on MPs. The proportion and number of non-classical monocytes were significantly decreased in patients with SLE compared with HCs and in patients with aSLE compared with patients with the inactive disease. Non-classical monocytes obtained from patients with SLE exhibited increased levels of CD64 associated with MPs-IgG +, MPs-C1q +, total circulating ICs-IgG +, and disease activity. The direct effects of MPs and MPs-IgG + on monocytes were evaluated in cell culture. Monocytes from both HCs and patients bound to and internalized MPs and MPs-IgG + independent of CD64. These vesicles derived from platelets (PMPs), mainly PMPs-IgG +, activated monocytes in vitro and increased the expression of CD69, CD64, and pro-inflammatory cytokines such as IL-1β, TNF-α, and IFN-α. Therefore, MPs are one of the most representative sources of the total amount of circulating ICs-IgG + in patients with SLE. MPs-IgG + are associated with SLE activity, and PMPs-IgG + stimulate monocytes, changing their phenotype and promoting pro-inflammatory responses related to disease activity.

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Patients with rheumatoid arthritis (RA) and autoantibodies, such as rheumatoid factor and those against cyclic citrullinated peptides, are designated as seropositive and have a more severe disease with worse prognosis than seronegative RA patients. Understanding the factors that participate in systemic inflammation, in addition to articular commitment, would allow better treatment approaches for prevention of RA comorbidities and disease reactivation. We evaluated whether monocyte subsets and extracellular vesicles (EVs) could contribute to this phenomenon. Seropositive patients had higher levels of proinflammatory cytokines than those of seronegative patients and healthy controls (HCs); however, this systemic inflammatory profile was unrelated to disease activity. High frequencies of circulating EVs positive for IgG, IgM, CD41a, and citrulline, together with altered counts and receptor expression of intermediate monocytes, were associated with systemic inflammation in seropositive patients; these alterations were not observed in seronegative patients, which seem to be more similar to HCs. Additionally, the EVs from seropositive patients were able to activate mononuclear phagocytes in vitro, and induced proinflammatory cytokines that were comparable to the inflammatory response observed at the systemic level in seropositive RA patients; therefore, all of these factors may contribute to the greater disease severity that has been described in these patients.

Objective. In various chronic inflammatory processes, both the proportion and numbers of monocyte subsets are altered. In systemic lupus erythematosus (SLE), this has not been clearly determined. The monocyte subpopulations in patients with SLE, patients with other autoimmune diseases, and healthy controls were evaluated. The effects of nonclassic monocytes and apoptotic cells (ACs) on the differentiation and function of CD14؉؉CD16؊ monocytes were also studied.Methods. Monocyte subpopulations derived from the blood samples of SLE patients (n ‫؍‬ 88), patients with other autoimmune diseases (n ‫؍‬ 37), and healthy control subjects (n ‫؍‬ 61) were separated by fluorescence-activated cell sorting. To evaluate the effect of CD14؉CD16؉؉ monocytes and ACs on the differentiation of CD14؉؉CD16؊ monocytes, we developed a coculture model of highly purified sorted monocyte subpopulations, which were reconstituted with defined proportions of CD14؉؉CD16؊ and CD14؉CD16؉؉ monocytes in the presence or absence of ACs. After differentiation into macrophages, CD3؉ lymphocytes were added, and the proliferating cells and CD3؉ IFN␥؉ cells were evaluated. A cytokine bead array panel was used to test the coculture supernatants.Results. There was a reduction in CD14؉CD16؉؉ monocytes in patients with active SLE. Monocytes from SLE patients had decreased expression of HLA-DR and decreased ability to bind and phagocytize ACs. In healthy controls, but not SLE patients, treatment with macrophages derived from CD14؉CD16؉؉ monocytes reduced T cell proliferation and proliferating CD3؉IFN␥؉ cells and increased the accumulation of tumor necrosis factor ␣, interleukin-10 (IL-10), and IL-1␤.Conclusion. Our findings show that CD14؉ CD16؉؉ monocytes, a population that is reduced and nonfunctional in SLE patients, have modulatory effects on CD14؉؉CD16؊ monocytes and T cells.

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