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  1. Article: Animal models of the antiphospholipid syndrome.

    Radway-Bright, E L / Inanc, M / Isenberg, D A

    Rheumatology (Oxford, England)

    1999  Volume 38, Issue 7, Page(s) 591–601

    Abstract: The antiphospholipid antibody syndrome (APS) is characterized by thrombocytopenia, recurrent thromboembolic phenomena and recurrent fetal loss, in association with anticardiolipin antibodies (aCL) and/or lupus anticoagulant (LA). Owing to the ethical and ...

    Abstract The antiphospholipid antibody syndrome (APS) is characterized by thrombocytopenia, recurrent thromboembolic phenomena and recurrent fetal loss, in association with anticardiolipin antibodies (aCL) and/or lupus anticoagulant (LA). Owing to the ethical and practical restrictions of experimentation on humans, we have to look to animal experimentation to broaden our knowledge of the pathogenesis and management of APS. Work has been carried out predominantly on strains of naive mice in which APS has been induced, passively and actively, using autoantibodies, autoantigens and other antigens. Studies of autoimmune-prone mice and naive rabbits are present in the literature, to a lesser degree. We review the various animal models of the pathogenesis of APS, whether spontaneous or induced, which have been developed over the years. Although several of the models have provided insights into the relationship between antiphospholipid antibodies and fetal loss, very few give guidance to explain the link with thrombosis. Novel or experimental therapeutic regimens have to be tested on appropriate animal models before any kind of human clinical trials may proceed. The regimens devised thus far are also reviewed.
    MeSH term(s) Animals ; Antiphospholipid Syndrome/complications ; Antiphospholipid Syndrome/physiopathology ; Antiphospholipid Syndrome/therapy ; Disease Models, Animal ; Fetal Death/etiology ; Humans ; Mice ; Rabbits ; Thrombosis/etiology
    Language English
    Publishing date 1999-07
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1464822-2
    ISSN 1462-0332 ; 1462-0324
    ISSN (online) 1462-0332
    ISSN 1462-0324
    DOI 10.1093/rheumatology/38.7.591
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: beta 2-Glycoprotein I and anti-beta 2-glycoprotein I antibodies: where are we now?

    Inanç, M / Radway-Bright, E L / Isenberg, D A

    British journal of rheumatology

    1997  Volume 36, Issue 12, Page(s) 1247–1257

    Abstract: beta 2-Glycoprotein I (beta 2-GPI), a plasma protein with in vitro anticoagulant properties, has been recognized to have an important role in the antiphospholipid syndrome (APS) as a cofactor and an (co)antigen in ELISA assays. Although beta 2-GPI levels ...

    Abstract beta 2-Glycoprotein I (beta 2-GPI), a plasma protein with in vitro anticoagulant properties, has been recognized to have an important role in the antiphospholipid syndrome (APS) as a cofactor and an (co)antigen in ELISA assays. Although beta 2-GPI levels were found to be increased in some patients with APS, the clinical value of measuring beta 2-GPI levels in APS is not known. Several reports have suggested that anti-beta 2-GPI antibodies may be a marker for the APS and might be more specific for the vascular complications of the APS than anticardiolipin antibodies. There have been major discoveries about phospholipid (PL) and antibody binding sites on beta 2-GPI, although more studies are needed. Reports of changes in cell membrane PL composition or exposure of other anionic molecules by apoptosis, cell activation and oxidative injury suggest mechanisms to explain beta 2-GPI binding and the generation of cryptic epitopes for aPL/anti-beta 2-GPI antibodies.
    MeSH term(s) Antiphospholipid Syndrome/blood ; Antiphospholipid Syndrome/immunology ; Autoantibodies/immunology ; Autoantibodies/physiology ; Autoantigens/immunology ; Epitope Mapping ; Glycoproteins/blood ; Glycoproteins/chemistry ; Glycoproteins/immunology ; Glycoproteins/physiology ; Humans ; Lupus Erythematosus, Systemic/blood ; Lupus Erythematosus, Systemic/immunology ; Membrane Glycoproteins/immunology ; beta 2-Glycoprotein I
    Chemical Substances Autoantibodies ; Autoantigens ; Glycoproteins ; Membrane Glycoproteins ; beta 2-Glycoprotein I
    Language English
    Publishing date 1997-12
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 605508-4
    ISSN 0263-7103
    ISSN 0263-7103
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: The prevalence of antibodies to anionic phospholipids in patients with the primary antiphospholipid syndrome, systemic lupus erythematosus and their relatives and spouses.

    Radway-Bright, E L / Ravirajan, C T / Isenberg, D A

    Rheumatology (Oxford, England)

    2000  Volume 39, Issue 4, Page(s) 427–431

    Abstract: Objectives: Antiphospholipid antibodies (aPL) have been associated with syndromes involving thrombosis, fetal loss and thrombocytopenia. Genetic and environmental conditions are among the factors attributed to the cause of autoimmune diseases such as ... ...

    Abstract Objectives: Antiphospholipid antibodies (aPL) have been associated with syndromes involving thrombosis, fetal loss and thrombocytopenia. Genetic and environmental conditions are among the factors attributed to the cause of autoimmune diseases such as the antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). The aim of this study was to determine whether these factors determine the prevalence of aPL.
    Methods: Three groups of patients were tested for the presence of IgG, IgM and IgA anticardiolipin (aCL), antiphosphatidylinositol (aPI), antiphosphatidylglycerol (aPG) and antiphosphatidylserine (aPS) antibodies: (i) patients with primary APS (PAPS); (ii) patients with SLE and secondary APS; and (iii) patients with SLE without APS. First-degree relatives and spouses of patients with SLE/APS were also tested for circulating aPL.
    Results: IgG aPL were particularly prevalent in patients with PAPS. IgG aPI and aCL were more prevalent in patients with PAPS than the IgM equivalents (P < 0.0001). Notably, none of the patients with PAPS had IgA aPL. A significantly higher number of relatives of patients with SLE/APS possessed IgG aPL than the normal controls. Except for aPG (P < 0.03), the prevalence of these antibodies in the relatives was not significantly different from patients with SLE/APS. The relatives also had significantly higher prevalence of IgG aPI, aPS and aCL antibodies than IgM aPL antibodies. In contrast, the prevalence of IgG aPL in the spouses was no different than in the healthy controls.
    Conclusions: Genetic factors, shared by patients and their relatives, seem to have some effect on the prevalence of aPL in the subjects studied, while environmental factors shared by spouses appear to have no influence.
    MeSH term(s) Adult ; Antibodies, Antiphospholipid/analysis ; Antibodies, Antiphospholipid/immunology ; Antiphospholipid Syndrome/genetics ; Antiphospholipid Syndrome/immunology ; Case-Control Studies ; Female ; Humans ; Immunoglobulin A/analysis ; Immunoglobulin G/analysis ; Immunoglobulin M/analysis ; Lupus Erythematosus, Systemic/genetics ; Lupus Erythematosus, Systemic/immunology ; Male ; Pedigree ; Prevalence ; Spouses
    Chemical Substances Antibodies, Antiphospholipid ; Immunoglobulin A ; Immunoglobulin G ; Immunoglobulin M
    Language English
    Publishing date 2000-04
    Publishing country England
    Document type Journal Article
    ZDB-ID 1464822-2
    ISSN 1462-0332 ; 1462-0324
    ISSN (online) 1462-0332
    ISSN 1462-0324
    DOI 10.1093/rheumatology/39.4.427
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Antiphospholipid antibodies are induced by in vitro fertilization and correlate with paraoxonase activity and total antioxidant capacity of plasma in infertile women.

    Delgado Alves, J / Radway-Bright, E L / Lee, S / Grima, B / Hothersall, J / Ravirajan, C T / Isenberg, D A

    Lupus

    2005  Volume 14, Issue 5, Page(s) 373–380

    Abstract: The objectives of this study were to determine whether antiphosholipid antibodies are associated with in vitro fertilization (IVF), and assess the potential biological effects of these antibodies. Sera from seventy infertile women (18 before IVF, 13 ... ...

    Abstract The objectives of this study were to determine whether antiphosholipid antibodies are associated with in vitro fertilization (IVF), and assess the potential biological effects of these antibodies. Sera from seventy infertile women (18 before IVF, 13 submitted to one IVF cycle and 39 after three cycles) and 28 healthy controls were collected. Anticardiolipin (anti-CL) and antiphosphatidylserine (anti-PS) antibodies, paraoxonase (PON) and Total Anti-oxidant Capacity of plasma (TAC) were measured. Anti-CL and anti-PS titres were significantly increased in treated patients compared with patients before treatment or controls (P < 0.001). There were no differences regarding anti-CL and anti-PS titres between controls and untreated patients nor when different types of infertility were considered. PON activity and TAC were significantly reduced in treated patients when compared to untreated and controls (P < 0.001; P < 0.002). PON correlated inversely with anti-CL and anti-PS IgG (r = -0.734; P < 0.001) and directly with TAC (r = 0.720, P < 0.001). In conclusion PON activity is decreased in women submitted to IVF treatment and is associated with the presence of antiphospholipid antibodies. These factors might contribute to the increased oxidative status found in these patients.
    MeSH term(s) Antibodies, Anticardiolipin/blood ; Antibodies, Antiphospholipid/biosynthesis ; Antibodies, Antiphospholipid/blood ; Antioxidants/metabolism ; Aryldialkylphosphatase/blood ; Autoantibodies/blood ; Case-Control Studies ; Female ; Fertilization in Vitro ; Humans ; Infertility, Female/immunology ; Infertility, Female/metabolism ; Infertility, Female/therapy ; Phosphatidylserines/immunology ; Regression Analysis
    Chemical Substances Antibodies, Anticardiolipin ; Antibodies, Antiphospholipid ; Antioxidants ; Autoantibodies ; Phosphatidylserines ; Aryldialkylphosphatase (EC 3.1.8.1)
    Language English
    Publishing date 2005
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1154407-7
    ISSN 0961-2033
    ISSN 0961-2033
    DOI 10.1191/0961203305lu2096oa
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Anti-beta2-glycoprotein I, anti-prothrombin and anticardiolipin antibodies in a longitudinal study of patients with systemic lupus erythematosus and the antiphospholipid syndrome.

    Inanç, M / Donohoe, S / Ravirajan, C T / Radway-Bright, E L / Mackie, I / Machin, S / Isenberg, D A

    British journal of rheumatology

    1998  Volume 37, Issue 10, Page(s) 1089–1094

    Abstract: Objective: To determine anti-beta2 glycoprotein-I (anti-beta2GPI) and anti-prothrombin (anti-ProT) antibody levels, and the IgG subclass distribution of anti-beta2GPI antibodies, in serial samples from patients with systemic lupus erythematosus (SLE) ... ...

    Abstract Objective: To determine anti-beta2 glycoprotein-I (anti-beta2GPI) and anti-prothrombin (anti-ProT) antibody levels, and the IgG subclass distribution of anti-beta2GPI antibodies, in serial samples from patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) having initial or recurrent thrombotic/neurological (T/N) events during the study period. To investigate the correlations between these antibodies and beta2GPI antigen, anticardiolipin antibody (aCL), anti-double-stranded (ds) DNA, C3 levels and disease activity.
    Methods: Fifty serum samples were identified from seven patients with SLE who had had T/N events during the follow-up from a cohort under long-term follow-up. IgG anti-beta2GPI, anti-ProT, aCL, IgG subclasses of anti-beta2GPI and beta2GPI antigen levels were determined by ELISA. Corresponding disease activity [British Isles Lupus Assessment Group (BILAG)], anti-dsDNA and C3 levels were compared.
    Results: IgG anti-beta2GPI antibody levels were elevated in six of the patients before and after the T/N events with less marked fluctuations than aCL antibody levels. The predominant subclass of anti-beta2GPI antibodies was IgG2 before and after the T/N events. IgG anti-ProT antibodies were negative in all cases. There was a significant but weak correlation between anti-beta2GPI and aCL antibodies. No correlation was found between disease activity and IgG anti-beta2GPI antibody and beta2GPI antigen levels. There were fluctuations in beta2GPI antigen levels and a trend to increase after T/N events was observed in some patients.
    Conclusion: Most of the patients with a T/N event during the study period had IgG anti-beta2GPI, but not IgG anti-ProT antibodies. Many IgG aCL-negative samples were found to have IgG anti-beta2GPI activity during the follow-up period. The predominant subclass of IgG anti-beta2GPI was IgG2, which may have importance in the pathogenesis of APS. beta2GPI antigen levels were found to be increased in some patients with SLE after T/N events. IgG anti-beta2GPI antibodies may be used as an adjunctive marker of future T/N events in patients with SLE and APS with aCL antibodies and lupus anticoagulant.
    MeSH term(s) Adult ; Antibodies, Anticardiolipin/analysis ; Antibodies, Antinuclear/blood ; Antiphospholipid Syndrome/complications ; Antiphospholipid Syndrome/immunology ; Cerebrovascular Disorders/blood ; Cerebrovascular Disorders/complications ; Complement C3/analysis ; Enzyme-Linked Immunosorbent Assay ; Female ; Glycoproteins/immunology ; Humans ; Immunoglobulin G/analysis ; Immunoglobulin M/analysis ; Longitudinal Studies ; Lupus Erythematosus, Systemic/complications ; Lupus Erythematosus, Systemic/immunology ; Middle Aged ; Prothrombin/immunology ; Thrombosis/blood ; Thrombosis/complications ; beta 2-Glycoprotein I
    Chemical Substances Antibodies, Anticardiolipin ; Antibodies, Antinuclear ; Complement C3 ; Glycoproteins ; Immunoglobulin G ; Immunoglobulin M ; beta 2-Glycoprotein I ; Prothrombin (9001-26-7)
    Language English
    Publishing date 1998-10
    Publishing country England
    Document type Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 605508-4
    ISSN 0263-7103
    ISSN 0263-7103
    Database MEDical Literature Analysis and Retrieval System OnLINE

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