title: Changes in regulation of human monocyte proteins in response to IgG from patients with antiphospholipid syndrome.
abstract: The effects of immunoglobulin G (IgG) from patients with the antiphospholipid syndrome (APS) upon monocyte activation have not been fully characterized. We carried out a comprehensive proteomic analysis of human monocytes treated with IgG from patients with different manifestations of the APS. Using 2-dimensional differential gel electrophoresis (2D DiGE), 4 of the most significantly regulated proteins (vimentin [VIM], zinc finger CCH domain-containing protein 18, CAP Gly domain-containing linker protein 2, and myeloperoxidase) were differentially regulated in monocytes treated with thrombotic or obstetric APS IgG, compared with healthy control (HC) IgG. These findings were confirmed by comparing monocytes isolated from APS patients and HC. Anti-VIM antibodies (AVAs) were significantly increased in 11 of 27 patients (40.7%) with APS. VIM expression on HC monocytes was stimulated more strongly by APS IgG from patients with higher-avidity serum AVA. We further characterized the proteome of thrombotic APS IgG-treated monocytes using a label-free proteomics technique. Of 12 proteins identified with the most confidence, 2 overlapped with 2D DiGE and many possessed immune response, cytoskeletal, coagulation, and signal transduction functions which are all relevant to APS and may therefore provide potential new therapeutic targets of this disease.
authors.affiliation: Centre for Rheumatology Research, Division of Medicine, University College London and Department of Medicine, Rayne Institute, London, United Kingdom;
authors.forename: Vera M
authors.initials: VM
authors.lastname: Ripoll
authors.affiliation: Centre for Rheumatology Research, Division of Medicine, University College London and Department of Medicine, Rayne Institute, London, United Kingdom;
authors.forename: Anastasia
authors.initials: A
authors.lastname: Lambrianides
authors.affiliation: Division of Rheumatology, Department of Medicine, University of Texas Medical Branch, Galveston, TX;
authors.forename: Silvia S
authors.initials: SS
authors.lastname: Pierangeli
authors.affiliation: Centre for Rheumatology Research, Division of Medicine, University College London and Department of Medicine, Rayne Institute, London, United Kingdom;
authors.forename: Katie
authors.initials: K
authors.lastname: Poulton
authors.affiliation: Centre for Rheumatology Research, Division of Medicine, University College London and Department of Medicine, Rayne Institute, London, United Kingdom; Arthritis Research UK Centre for Adolescent Rheumatology, University College London, London, United Kingdom;
authors.forename: Yiannis
authors.initials: Y
authors.lastname: Ioannou
authors.affiliation: Biological Mass Spectrometry Centre University College London Institute of Child Health, London, United Kingdom; and.
authors.forename: Wendy E
authors.initials: WE
authors.lastname: Heywood
authors.affiliation: Biological Mass Spectrometry Centre University College London Institute of Child Health, London, United Kingdom; and.
authors.forename: Kevin
authors.initials: K
authors.lastname: Mills
authors.affiliation: Birkbeck, University of London, London, United Kingdom.
authors.forename: David S
authors.initials: DS
authors.lastname: Latchman
authors.affiliation: Centre for Rheumatology Research, Division of Medicine, University College London and Department of Medicine, Rayne Institute, London, United Kingdom;
authors.forename: David A
authors.initials: DA
authors.lastname: Isenberg
authors.affiliation: Centre for Rheumatology Research, Division of Medicine, University College London and Department of Medicine, Rayne Institute, London, United Kingdom;
authors.forename: Anisur
authors.initials: A
authors.lastname: Rahman
authors.affiliation: Centre for Rheumatology Research, Division of Medicine, University College London and Department of Medicine, Rayne Institute, London, United Kingdom;
authors.forename: Ian P
authors.initials: IP
authors.lastname: Giles
mesh_terms: D000328:Adult; D016736:Antiphospholipid Syndrome / Q000097:blood / Q000276:immunology*; D015153:Blotting, Western; D002478:Cells, Cultured; D002853:Chromatography, Liquid; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D020543:Proteome / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053719:Tandem Mass Spectrometry; D020298:U937 Cells
chemical_list: D007074:Immunoglobulin G; D020543:Proteome