The relationship between plasma microparticles and disease manifestations in patients with systemic sclerosis.
OBJECTIVE: Microparticles are small, membrane-coated vesicles that can serve as novel signaling structures between cells. The aim of the present study was to analyze the profile of microparticles in the blood of patients with systemic sclerosis (SSc; scleroderma) and healthy controls. METHODS: The study population consisted of 37 patients with SSc and 15 healthy subjects of comparable sex and age. Microparticles were isolated from plasma by high-speed differential centrifugation. Microparticles were stained with monoclonal antibodies against cell type-specific markers and were quantified by fluorescence-activated cell sorting analyses. RESULTS: The total number of microparticles was strongly increased in patients with SSc compared with healthy controls (mean +/- SEM 88.0 +/- 4.8 x 10(5) microparticles/ml plasma versus 42.3 +/- 9.4 x 10(5) microparticles/ml plasma; P < 0.001). Similarly, significant increases were found for microparticles derived from platelets, endothelial cells, monocytes, and T cells, reflecting the activation of these cells in SSc. Platelets were the most common source of microparticles in the blood of patients with SSc (66.9 +/- 5.2% of all microparticles) and healthy donors, followed by microparticles derived from endothelial cells (8.8 +/- 0.9% in SSc patients). The modified Rodnan skin thickness score (MRSS) was inversely correlated with the total number of microparticles. Furthermore, patients with cutaneous ulcers showed a significantly lower total number of microparticles. In multivariate analysis, an additive model of age, C-reactive protein, MRSS, and subtype of disease accounted for 55% of the variability of the total microparticle count (r = 0.744). CONCLUSION: The number of microparticles from different cellular sources is increased in the blood of SSc patients. Considering their role as important mediators of intercellular communication, microparticles could be a novel link between activated cellular compartments in the pathogenesis of SSc.
Guiducci, S; Distler, JHW; Jüngel, A; Huscher, D; Huber, LC; Michel, BA; Gay, RE; Pisetsky, DS; Gay, S; Matucci-Cerinic, M; Distler, O
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