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Nat Clin Pract Rheumatol ; 4(4): 192-9, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18285765


The discovery that antiphospholipid antibodies recognize plasma proteins that bind to phospholipids rather than recognizing phospholipids themselves has been a major advance in research into antiphospholipid syndrome (APS). It is now established that beta2-glycoprotein I (beta2 GPI) is the most important antigen for antiphospholipid antibodies. However, the possible pathologic mechanism is still much debated. This is mainly because not all patients with anti-beta2 GPI antibodies show clinical symptoms that are related to APS. Several reports indicate that anti-beta2 GPI antibodies with lupus anticoagulant (LA) activity are clinically of much importance. Most patients with LA caused by anti-beta2 GPI antibodies suffer from thrombosis as a result of recognition of the first domain of beta2 GPI by these antibodies. In the search for a pathologic mechanism that might explain the high occurrence of thrombosis in patients with anti-domain I antibodies (LA-causing anti-beta2 GPI antibodies), it was found that these antibodies show increased resistance to the anticoagulant activity of annexin A5. We have shown that the same population of antibodies also displays increased resistance to activated protein C. Owing to the diversity of clinical symptoms related to APS, it is likely that other pathologic mechanisms also contribute to the occurrence of APS-related symptoms.

Anticorpos Antifosfolipídeos/imunologia , Síndrome Antifosfolipídica/imunologia , Anexina A5/metabolismo , Anticorpos Antifosfolipídeos/sangue , Anticorpos Antifosfolipídeos/história , Anticoagulantes/metabolismo , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/diagnóstico , Resistência a Medicamentos , História do Século XX , Humanos , Inibidor de Coagulação do Lúpus/sangue , Inibidor de Coagulação do Lúpus/imunologia , Trombose/diagnóstico , Trombose/imunologia , Trombose/metabolismo , beta 2-Glicoproteína I/imunologia
Autoimmunity ; 38(1): 33-8, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15804703


The anticardiolipin (aCL) antibody test was first established in 1983, using cardiolipin (negatively charged phospholipid) as an antigen in a solid-phase immunoassAy. It was first applied to the study of systemic lupus erythematosus patients, and was found associated with thromboses and recurrent pregnancy losses. The wide use of this test was determinant in the definition of the "aCL or antiphospholipid syndrome" (APS).Later, it was demonstrated that aCL antibodies do not recognize anionic phospholipids but are directed against plasma proteins bound to anionic phospholipids, mainly beta-2-glycoprotein I, which is now considered as the autoantigen in APS. Anti-beta-2-glycoprotein I (anti-beta2GPI) is not yet accepted as a serological criterion for APS, but most investigators would consider a patient with anti-beta2GPI antibodies and clinical features of APS to have the syndrome. aCL and anti-beta2GPI are a heterogeneous group of antibodies with different clinical significances and can be present in different autoimmune diseases as well as in infectious diseases.

Anticorpos Anticardiolipina/sangue , Anticorpos Antifosfolipídeos/sangue , Glicoproteínas/imunologia , Anticorpos Anticardiolipina/história , Anticorpos Antifosfolipídeos/história , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/imunologia , Doenças Autoimunes/imunologia , Feminino , História do Século XX , Humanos , Gravidez , beta 2-Glicoproteína I
J Reprod Immunol ; 36(1-2): 123-42, 1997 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-9430743


Antiphospholipid antibodies are a family of autoantibodies including lupus anticoagulant and anticardiolipin antibodies that appear to react with negatively charged phospholipids. These antibodies induce thrombosis and pregnancy complications including recurrent stillbirth, recurrent miscarriage, pre-eclampsia and intra-uterine growth retardation. Recent evidence indicates that antiphospholipid antibodies do not bind directly to phospholipid but rather to phospholipid-binding proteins or to a combination of phospholipid and phospholipid-binding proteins. This opens the possibility that antiphospholipid antibodies may be pathogenic by disrupting the function of phospholipid-binding proteins rather than membrane phospholipid. The antigenic role of one phospholipid-binding protein, beta 2 glycoprotein, has been studied in the greatest detail and is reviewed. Despite being highly conserved and expressed at high levels, the physiological function of beta 2 glycoprotein 1 remains unknown. However, a number of putative roles have been proposed which allow speculation as to the mechanism by which antiphospholipid antibodies may disrupt haemostasis and pregnancy.

Anticorpos Antifosfolipídeos/fisiologia , Glicoproteínas/fisiologia , Complicações na Gravidez/etiologia , Complicações na Gravidez/imunologia , Animais , Anticorpos Antifosfolipídeos/história , Modelos Animais de Doenças , Feminino , História do Século XX , Humanos , Camundongos , Fosfolipídeos/imunologia , Fosfolipídeos/metabolismo , Placenta/imunologia , Placenta/fisiologia , Gravidez , Complicações na Gravidez/fisiopatologia , Terminologia como Assunto , beta 2-Glicoproteína I