Distinct features of circulating microparticles and their relationship to clinical manifestations in systemic lupus erythematosus.
Nielsen CT., Østergaard O., Johnsen C., Jacobsen S., Heegaard NHH.
OBJECTIVE: Characterization of the abundance, origin, and annexin V (AnxV)-binding capabilities of circulating microparticles (MPs) in SLE patients and healthy controls and to determine any associations with clinical parameters. METHODS: Seventy unselected SLE patients and 29 sex- and age-matched healthy control subjects were included in the study. MPs were isolated from citrate-treated plasma and characterized by flow cytometry using AnxV or antibodies to platelet, leukocyte, or endothelial cell surface markers. RESULTS: SLE patients had significantly increased concentrations of AnxV-nonbinding (AnxV-) MPs (P<0.0001), while the concentrations of total MPs (P=0.011) and AnxV-binding (AnxV+) MPs (P<0.0001) were decreased, as compared with controls. Based on flow cytometric characteristics, 2 subgroups of AnxV- MPs could be discerned: AnxV- cell-derived MPs (CDMPs) and AnxV- MPs of unknown nature (UNMPs). Both fractions were significantly increased in SLE patients (P=0.007 and P=0.0018, respectively). Platelet- and leukocyte-derived MPs were decreased in the SLE patients (P<0.0001), whereas no difference was observed for endothelial cell-derived MPs (P=0.14). The concentrations of AnxV- CDMPs correlated with the concentrations of endothelial cell-derived MPs, the disease activity score, active nephritis, hypertension, history of arterial thrombosis, and triglyceride levels (P<0.05 for all comparisons). CONCLUSION: The concentrations and composition of MPs in SLE patients differ markedly from those in healthy subjects. Overall MP numbers were significantly decreased, but two distinct subpopulations of AnxV- MPs were significantly increased. These findings call for further characterization of MPs in SLE patients to elucidate their role in disease pathogenesis.