title: Circulating microparticle subpopulations in systemic lupus erythematosus are affected by disease activity.
abstract: BACKGROUND
  Immune cells under chronic inflammation shed microparticles (MPs) that could fuel the inflammatory responses and atherosclerosis typically presented in systemic lupus erythematosus (SLE). This study analyzes total and subset-specific MPs from SLE patients and their possible influence on clinical features, leukocyte activation and serum cytokines.
  
  
  METHODS
  Total MPs and those derived from platelets, endothelial cells, monocytes, granulocytes and T-cells were quantified in plasma of 106 SLE patients and 33 healthy controls by flow cytometry. MP amounts were analyzed according to clinical manifestations, blood leukocyte populations and circulating cytokines (IFNα, TNFα, IL-10, BLyS, IL-17, IL-1β, CXCL10, CCL-2, CCL3, leptin). Finally, the in vitro effect of SLE-isolated MPs on the leukocyte activation status was analyzed.
  
  
  RESULTS
  Total circulating MPs in SLE patients were related to increased disease duration and the presence of cardiovascular disease. Furthermore, patients displayed increased counts of MPs from platelets, monocytes and T-lymphocytes, especially in SLE patients with disease activity or with TNFαhigh-profile. Accordingly, MPs were associated with increased expression of activation markers in blood T-cells and monocytes. Finally, analyses propose a role of glucocorticoids in MPs generation and leukocyte activation since both fresh and cultured T-cells under this treatment presented higher IL-10 and CD25 production.
  
  
  CONCLUSIONS
  The altered profile of subset-specific SLE-MPs was influenced by the disease activity and altered status of leukocyte native cells, also associated with a TNFαhigh-profile.
  SLE patients, especially those with disease activity, displayed increased counts of MPs derived from platelets, monocytes and T-lymphocytes, which were more frequently found in TNFαhigh-type patients. The origin of such SLE-MP subsets seems to be related to the over-activated status of T-cells and monocytes characteristic of these patients. Ex vivo and in vitro analyses propose a role of glucocorticoids in the generation of circulating MPs and leukocyte activation in SLE patients.
authors.affiliation: Department of Functional Biology, Immunology Area, Faculty of Medicine, University of Oviedo, Oviedo, Spain. Electronic address: lopezpatricia@uniovi.es.
authors.forename: Patricia
authors.initials: P
authors.lastname: López
authors.affiliation: Department of Functional Biology, Immunology Area, Faculty of Medicine, University of Oviedo, Oviedo, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Rodríguez-Carrio
authors.affiliation: Department of Internal Medicine, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Aleida
authors.initials: A
authors.lastname: Martínez-Zapico
authors.affiliation: Department of Internal Medicine, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Caminal-Montero
authors.affiliation: Department of Functional Biology, Immunology Area, Faculty of Medicine, University of Oviedo, Oviedo, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Suárez
mesh_terms: D000328:Adult; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000175:diagnosis / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D012189:Retrospective Studies; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
keywords: Cardiovascular disease; Cytokines; Endothelial function; Glucocorticoids; Plasma microparticles