Patricia López1, Javier Rodríguez-Carrio2, Aleida Martínez-Zapico3, Luis Caminal-Montero3, Ana Suárez2. 1. Department of Functional Biology, Immunology Area, Faculty of Medicine, University of Oviedo, Oviedo, Spain. Electronic address: lopezpatricia@uniovi.es. 2. Department of Functional Biology, Immunology Area, Faculty of Medicine, University of Oviedo, Oviedo, Spain. 3. Department of Internal Medicine, Hospital Universitario Central de Asturias, Oviedo, Spain.
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. TRANSLATIONAL RESULTS: 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.
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 SLEpatients 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 SLEpatients 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 SLEpatients 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 SLEpatients 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. TRANSLATIONAL RESULTS:SLEpatients, 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 SLEpatients.
Authors: Petrus Linge; Paul R Fortin; Christian Lood; Anders A Bengtsson; Eric Boilard Journal: Nat Rev Rheumatol Date: 2018-03-21 Impact factor: 20.543
Authors: Martin Em Parsons; Karen O'Connell; Seamus Allen; Karl Egan; Paulina B Szklanna; Christopher McGuigan; Fionnuala Ní Áinle; Patricia B Maguire Journal: Mult Scler J Exp Transl Clin Date: 2017-12-26