Paul R Fortin1,2, Nathalie Cloutier3,4, Vincent Bissonnette3,4, Ellie Aghdassi3,4, Lihi Eder3,4, David Simonyan3,4, Nathalie Laflamme3,4, Eric Boilard1,2. 1. From the Centre de recherche du CHU de Québec - Université Laval, Axe Maladies Infectieuses et Immunitaires and Division of Rheumatology, Department of Medicine, Université Laval; Centre de Recherche en Rhumatologie et Immunologie, Centre de Recherche du CHU de Québec- Université Laval and Faculté de Médecine, Université Laval; Centre de recherche du CHU de Québec - Université Laval, Plateforme de recherche clinique et évaluative, Université Laval, Québec City, Québec; Dalla Lana School of Public Health, University of Toronto, Division of Neurology, University Health Network, Toronto Western Hospital; Women's College Research Institute, Women's College Hospital and Department of Medicine, University of Toronto, Toronto, Ontario, Canada. eric.boilard@crchudequebec.ulaval.ca paul.fortin@crchudequebec.ulaval.ca. 2. P.R. Fortin, MD, MPH, FRCPC, Centre de recherche du CHU de Québec - Université Laval, Axe Maladies Infectieuses et Immunitaires and Division of Rheumatology, Department of Medicine, Université Laval; N. Cloutier, PhD, Centre de Recherche en Rhumatologie et Immunologie, Centre de Recherche du CHU de Québec - Université Laval, and Faculté de Médecine, Université Laval; V. Bissonnette, BSc, Centre de recherche du CHU de Québec - Université Laval, Axe Maladies Infectieuses et Immunitaires and Division of Rheumatology, Department of Medicine, Université Laval, and Centre de Recherche en Rhumatologie et Immunologie, Centre de Recherche du CHU de Québec - Université Laval; E. Aghdassi, PhD, RD, Dalla Lana School of Public Health, University of Toronto, Division of Neurology, University Health Network, Toronto Western Hospital; L. Eder, MD, PhD, Women's College Research Institute, Women's College Hospital, Department of Medicine, University of Toronto; D. Simonyan, MSc, Centre de recherche du CHU de Québec - Université Laval, Plateforme de recherche clinique et évaluative, and Faculté de Médecine, Université Laval; N. Laflamme, PhD, Centre de recherche du CHU de Québec - Université Laval, Plateforme de recherche clinique et évaluative, and Faculté de Médecine, Université Laval; E. Boilard, PhD, Centre de Recherche en Rhumatologie et Immunologie, Centre de Recherche du CHU de Québec - Université Laval, Faculté de Médecine, Université Laval. eric.boilard@crchudequebec.ulaval.ca paul.fortin@crchudequebec.ulaval.ca. 3. From the Centre de recherche du CHU de Québec - Université Laval, Axe Maladies Infectieuses et Immunitaires and Division of Rheumatology, Department of Medicine, Université Laval; Centre de Recherche en Rhumatologie et Immunologie, Centre de Recherche du CHU de Québec- Université Laval and Faculté de Médecine, Université Laval; Centre de recherche du CHU de Québec - Université Laval, Plateforme de recherche clinique et évaluative, Université Laval, Québec City, Québec; Dalla Lana School of Public Health, University of Toronto, Division of Neurology, University Health Network, Toronto Western Hospital; Women's College Research Institute, Women's College Hospital and Department of Medicine, University of Toronto, Toronto, Ontario, Canada. 4. P.R. Fortin, MD, MPH, FRCPC, Centre de recherche du CHU de Québec - Université Laval, Axe Maladies Infectieuses et Immunitaires and Division of Rheumatology, Department of Medicine, Université Laval; N. Cloutier, PhD, Centre de Recherche en Rhumatologie et Immunologie, Centre de Recherche du CHU de Québec - Université Laval, and Faculté de Médecine, Université Laval; V. Bissonnette, BSc, Centre de recherche du CHU de Québec - Université Laval, Axe Maladies Infectieuses et Immunitaires and Division of Rheumatology, Department of Medicine, Université Laval, and Centre de Recherche en Rhumatologie et Immunologie, Centre de Recherche du CHU de Québec - Université Laval; E. Aghdassi, PhD, RD, Dalla Lana School of Public Health, University of Toronto, Division of Neurology, University Health Network, Toronto Western Hospital; L. Eder, MD, PhD, Women's College Research Institute, Women's College Hospital, Department of Medicine, University of Toronto; D. Simonyan, MSc, Centre de recherche du CHU de Québec - Université Laval, Plateforme de recherche clinique et évaluative, and Faculté de Médecine, Université Laval; N. Laflamme, PhD, Centre de recherche du CHU de Québec - Université Laval, Plateforme de recherche clinique et évaluative, and Faculté de Médecine, Université Laval; E. Boilard, PhD, Centre de Recherche en Rhumatologie et Immunologie, Centre de Recherche du CHU de Québec - Université Laval, Faculté de Médecine, Université Laval.
Abstract
OBJECTIVE: Microparticles (MP) are small extracellular vesicles present in body fluids. MP originate from different cellular lineages, principally from platelets in blood, and may expose phosphatidylserine (PS). In systemic lupus erythematosus (SLE), MP harbor immunoglobulin G (IgG), thereby forming MP-containing immune complexes (mpIC). We aimed to verify an association between SLE disease activity, damage, and surrogate markers of atherosclerosis and MP harboring IgG, taking into account the platelet origin and PS exposure of MP. METHODS: MP expressing surface IgG, platelet antigen (CD41+), and PS were quantified using flow cytometry in plasma of 191 women with SLE. Carotid ultrasounds (US) were available in 113 patients. Spearman correlation analysis was used to analyze whether levels of MP were associated with the following outcomes: SLE Disease Activity Index 2000 (SLEDAI-2K), Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI), and carotid US plaques and intima-media thickness (CIMT) as surrogates for vascular damage. RESULTS: We found CD41+ MP harboring IgG present in SLE. A positive correlation was found between SLEDAI-2K and levels of CD41+ MP harboring IgG and exposing (p = 0.027) and non-exposing PS (p = 0.001). Conversely, SDI (p = 0.024) and CIMT (p = 0.016) correlated with concentrations of CD41- MP harboring IgG and exposing PS. Associations were independent of low-density lipoprotein cholesterol level, body mass index, and antimalarial drug use. CONCLUSION: Different subtypes of mpIC are produced in SLE and are associated with distinct clinical characteristics such as disease activity and vascular damage. The assessment of MP subtypes might serve for the design of predictive markers of disease activity and vascular damage in patients.
OBJECTIVE: Microparticles (MP) are small extracellular vesicles present in body fluids. MP originate from different cellular lineages, principally from platelets in blood, and may expose phosphatidylserine (PS). In systemic lupus erythematosus (SLE), MP harbor immunoglobulin G (IgG), thereby forming MP-containing immune complexes (mpIC). We aimed to verify an association between SLE disease activity, damage, and surrogate markers of atherosclerosis and MP harboring IgG, taking into account the platelet origin and PS exposure of MP. METHODS: MP expressing surface IgG, platelet antigen (CD41+), and PS were quantified using flow cytometry in plasma of 191 women with SLE. Carotid ultrasounds (US) were available in 113 patients. Spearman correlation analysis was used to analyze whether levels of MP were associated with the following outcomes: SLE Disease Activity Index 2000 (SLEDAI-2K), Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI), and carotid US plaques and intima-media thickness (CIMT) as surrogates for vascular damage. RESULTS: We found CD41+ MP harboring IgG present in SLE. A positive correlation was found between SLEDAI-2K and levels of CD41+ MP harboring IgG and exposing (p = 0.027) and non-exposing PS (p = 0.001). Conversely, SDI (p = 0.024) and CIMT (p = 0.016) correlated with concentrations of CD41- MP harboring IgG and exposing PS. Associations were independent of low-density lipoprotein cholesterol level, body mass index, and antimalarial drug use. CONCLUSION: Different subtypes of mpIC are produced in SLE and are associated with distinct clinical characteristics such as disease activity and vascular damage. The assessment of MP subtypes might serve for the design of predictive markers of disease activity and vascular damage in patients.
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