title: Circulating microparticles in patients with antiphospholipid antibodies: characterization and associations.
abstract: The antiphospholipid syndrome is characterized by venous or arterial thrombosis and/or recurrent fetal loss in the presence of circulating antiphospholipid antibodies. These antibodies cause activation of endothelial and other cell types leading to the release of microparticles with procoagulant and pro-inflammatory properties. The aims of this study were to characterize the levels of endothelial cell, monocyte or platelet derived, and tissue factor-bearing microparticles in patients with antiphospholipid antibodies, to determine the association of circulating microparticles with anticardiolipin and anti-β2-glycoprotein antibodies, and to define the cellular origin of microparticles that express tissue factor. Microparticle content within citrated blood from 47 patients with antiphospholipid antibodies and 144 healthy controls was analyzed within 2hours of venipuncture. Levels of Annexin-V, CD105 and CD144 (endothelial derived), CD41 (platelet derived) and tissue factor positive microparticles were significantly higher in patients than controls. Though levels of CD14 (monocyte-derived) microparticles in patient plasma were not significantly increased, increased levels of CD14 and tissue factor positive microparticles were observed in patients. Levels of microparticles that stained for CD105 and CD144 showed a positive correlation with IgG (R=0.60, p=0.006) and IgM anti-beta2-glycoprotein I antibodies (R=0.58, p=0.006). The elevation of endothelial and platelet derived microparticles in patients with antiphospholipid antibodies and their correlation with anti-β2-glycoprotein I antibodies suggests a chronic state of vascular cell activation in these individuals and an important role for β2-glycoprotein I in development of the pro-thrombotic state associated with antiphospholipid antibodies.
authors.affiliation: Department of Internal Medicine, Cleveland Clinic, Cleveland, OH 44195, United States.
authors.forename: Shruti
authors.initials: S
authors.lastname: Chaturvedi
authors.affiliation: St Joseph Cancer Institute, Tampa, FL, United States.
authors.forename: Erin
authors.initials: E
authors.lastname: Cockrell
authors.affiliation: United States Food and Drug Administration, Rockville, MD, United States.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Espinola
authors.affiliation: Department of Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, OH 44195, United States.
authors.forename: Linda
authors.initials: L
authors.lastname: Hsi
authors.affiliation: Department of Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, OH 44195, United States.
authors.forename: Stacey
authors.initials: S
authors.lastname: Fulton
authors.affiliation: Department of Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, OH 44195, United States.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Khan
authors.affiliation: Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH 44195, United States.
authors.forename: Liang
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, OH 44195, United States.
authors.forename: Fabio
authors.initials: F
authors.lastname: Fonseca
authors.affiliation: Department of Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, OH 44195, United States.
authors.forename: Suman
authors.initials: S
authors.lastname: Kundu
authors.affiliation: Department of Hematology and Medical Oncology, Cleveland Clinic, Cleveland, OH 44195, United States; Department of Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, OH 44195, United States. Electronic address: mccraek@ccf.org.
authors.forename: Keith R
authors.initials: KR
authors.lastname: McCrae
mesh_terms: D000328:Adult; D017153:Antibodies, Anticardiolipin / Q000097:blood; D017152:Antibodies, Antiphospholipid / Q000097:blood; D015703:Antigens, CD / Q000378:metabolism; D016736:Antiphospholipid Syndrome / Q000097:blood*; D001792:Blood Platelets / Q000166:cytology*; D015820:Cadherins / Q000378:metabolism; D055252:Cell-Derived Microparticles / Q000737:chemistry*; D000071063:Endoglin; D042783:Endothelial Cells / Q000166:cytology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D011956:Receptors, Cell Surface / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism*; D013927:Thrombosis / Q000097:blood; D053482:beta 2-Glycoprotein I / Q000097:blood*; D000099152:Cadherin 5
chemical_list: D017153:Antibodies, Anticardiolipin; D017152:Antibodies, Antiphospholipid; D015703:Antigens, CD; D015820:Cadherins; D000071063:Endoglin; D018950:Lipopolysaccharide Receptors; D011956:Receptors, Cell Surface; D013925:Thromboplastin; D053482:beta 2-Glycoprotein I; D000099152:Cadherin 5; C064206:ENG protein, human
keywords: Antiphospholipid; Endothelial cell; Microparticles; Platelet; Thrombosis