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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Pericleous, Charis Ruiz-Limón, Patricia Romay-Penabad, Zurina Marín, Ana Carrera Garza-Garcia, Acely Murfitt, Lucy Driscoll, Paul C. Latchman, David S. Isenberg, David A. Giles, Ian Ioannou, Yiannis Rahman, Anisur Pierangeli, Silvia S. |
| Description | Author Affiliation: Pericleous C ( Centre for Rheumatology Research, Division of Medicine, University College London, London, UK, Division of Rheumatology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA, Structural Biology, Medical Research Council National Institute for Medical Research and A); Ruiz-Limón P ( Centre for Rheumatology Research, Division of Medicine, University College London, London, UK, Division of Rheumatology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA, Structural Biology, Medical Research Council National Institute for Medical Research and A); Romay-Penabad Z ( Centre for Rheumatology Research, Division of Medicine, University College London, London, UK, Division of Rheumatology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA, Structural Biology, Medical Research Council National Institute for Medical Research and A); Marín AC ( Centre for Rheumatology Research, Division of Medicine, University College London, London, UK, Division of Rheumatology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA, Structural Biology, Medical Research Council National Institute for Medical Research and A); Garza-Garcia A ( Centre for Rheumatology Research, Division of Medicine, University College London, London, UK, Division of Rheumatology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA, Structural Biology, Medical Research Council National Institute for Medical Research and A); Murfitt L ( Centre for Rheumatology Research, Division of Medicine, University College London, London, UK, Division of Rheumatology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA, Structural Biology, Medical Research Council National Institute for Medical Research and A); Driscoll PC ( Centre for Rheumatology Research, Division of Medicine, University College London, London, UK, Division of Rheumatology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA, Structural Biology, Medical Research Council National Institute for Medical Research and A); Latchman DS ( Centre for Rheumatology Research, Division of Medicine, University College London, London, UK, Division of Rheumatology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA, Structural Biology, Medical Research Council National Institute for Medical Research and A); Isenberg DA ( Centre for Rheumatology Research, Division of Medicine, University College London, London, UK, Division of Rheumatology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA, Structural Biology, Medical Research Council National Institute for Medical Research and A); Giles I ( Centre for Rheumatology Research, Division of Medicine, University College London, London, UK, Division of Rheumatology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA, Structural Biology, Medical Research Council National Institute for Medical Research and A); Ioannou Y ( Centre for Rheumatology Research, Division of Medicine, University College London, London, UK, Division of Rheumatology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA, Structural Biology, Medical Research Council National Institute for Medical Research and A); Rahman A ( Centre for Rheumatology Research, Division of Medicine, University College London, London, UK, Division of Rheumatology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA, Structural Biology, Medical Research Council National Institute for Medical Research and A); Pierangeli SS ( Centre for Rheumatology Research, Division of Medicine, University College London, London, UK, Division of Rheumatology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA, Structural Biology, Medical Research Council National Institute for Medical Research and A) |
| Abstract | OBJECTIVE: IgG aPL against domain I of ß2-glycoprotein I (ß2GPI) [anti-DI (aDI)] is associated with the pathogenesis of APS, an autoimmune disease defined by thrombosis and pregnancy morbidity. To date, however, no study has demonstrated direct pathogenicity of IgG aDI in vivo. In this proof-of-concept study, we designed a novel system to affinity purify polyclonal aDI aPL in order to assess its prothrombotic ability in a well-characterized mouse microcirculation model for APS. METHODS: Two polyclonal IgG fractions were isolated from serum of a patient with APS, both with high aPL activity but differing in aDI activity (aDI-rich and aDI-poor). These IgG fractions were tested for their pathogenic ability in an in vivo mouse model of thrombosis. Male CD1 mice were injected intraperitoneally with either aDI-rich or aDI-poor IgG; as a control, IgG isolated from healthy serum was used. A pinch injury was applied to the right femoral vein and thrombus dynamics and tissue factor activity in isolated tissue were evaluated. RESULTS: Both aDI-rich and aDI-poor IgG retained aCL and anti-ß2GPI activity, while only aDI-rich IgG displayed high aDI activity, as defined by our in-house cut-offs for positivity in each assay. aDI-rich IgG induced significantly larger thrombi in vivo compared with aDI-poor IgG (P < 0.0001). Similarly, aDI-rich IgG significantly enhanced the procoagulant activity of carotid artery endothelium and peritoneal macrophages isolated from experimental animals (P < 0.01). CONCLUSION: These data directly demonstrate that the ability to cause thrombosis in vivo is concentrated in the aDI fraction of aPL. |
| File Format | HTM / HTML |
| ISSN | 14620324 |
| e-ISSN | 14620332 |
| DOI | 10.1093/rheumatology/keu360 |
| Journal | Rheumatology |
| Issue Number | 4 |
| Volume Number | 54 |
| Language | English |
| Publisher | Oxford University Press |
| Publisher Date | 2015-04-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Discipline Rheumatology Antibodies, Antiphospholipid Pharmacology Antiphospholipid Syndrome Chemically Induced Disease Models, Animal Immunoglobulin G Mice Thrombosis Beta 2-glycoprotein I Immunology Animals Complications Protein Structure, Tertiary Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology (medical) Rheumatology |
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