1,721,050 research outputs found
Antibodies and Diagnostic Tests in Antiphospholipid Syndrome
No full textThe current classification criteria for antiphospholipid syndrome (APS) recommend testing for three assays, namely antibodies against cardiolipin (aCL) and β2-glycoprotein I (anti-β2GPI) plus lupus anticoagulant (LA). β2GPIdependent antibodies are those mainly responsible for the positivity in the APS laboratory assays and for most of the pathogenic mechanisms involved in the syndrome. To overcome the technical limitations of APS assays and to identify a broader spectrum of patients, several tests have been assessed as additional laboratory tools: antibodies against domain I of β2GPI, aCL, anti-β2GPI IgA and antibodies against PT are among the most promising but still under evaluation. Other nonclassification/diagnostic autoantibodies have been described in APS, some directly contributing to the clinical manifestations (antibodies against proteins involved in hemostasis, anti-platelet and anti-endothelial cell antibodies) and some others reflecting the ongoing systemic autoimmunity characteristic of the syndrome (anti-nuclear, anti-mitochondrial, anti-red cell, anti-thyroid antibodies, and antibodies against plasma lipoproteins)
Innate immunity in the antiphospholipid syndrome : role of toll-like receptors in endothelial cell activation by antiphospholipid antibodies
No full textHumoral autoimmunity against endothelium : theory or reality?
No full textDespite the discovery of anti-endothelial cell antibodies (AECA) in a heterogeneous group of disorders characterized by endothelial damage, their pathogenic role is still debated. Experimental in vitro models indicate that they can either damage endothelial cells or trigger cell signaling by reacting with as yet undefined surface molecules. However, clinical studies suggest that, in addition to AECA, other pathogenic mechanisms are involved in the vasculitic process. Recently, antibodies specific for beta 2 glycoprotein I, the phospholipid-binding protein targeted by anti-phospholipid antibodies, have been shown to display anti-endothelial activity. These autoantibodies recognize beta 2 glycoprotein I adhered to the endothelium and induce a cell perturbation that might underlie the thrombophilic state of the anti-phospholipid syndrome
Update on the pathogenesis and treatment of the antiphospholipid syndrome
No full textPurpose of review Many advancements in our understanding of the pathogenic mechanisms of the antiphospholipid syndrome (APS) have been accomplished over the recent months. Such progresses are paralleled by the development of innovative pharmacological tools that could provide novel therapeutic windows in APS management. The most recent and innovative findings about the biologic effects of antiphospholipid antibodies (aPLs) and the treatment APS will be hereby critically appraised. Recent findings Antibodies against the domain I of b2 glycoprotein I (b2GPI) are increasingly recognized as the main pathogenic subset; pioneer therapeutic options exploiting the pathogenicity of anti-domain I antibodies have been developed. AnnexinA2 and toll-like receptor (TLR)4 have been identified as the main receptors for b2GPI/anti-b2GPI antibodies on target cells; additional co-receptors might include TLR1, TLR2 and TLR6. Upon binding, aPLs engage intracellular mediators as nuclear factor kappa B and mammalian target of rapamycin, which provide potential therapeutic targets. Current innovative treatment options include novel oral anticoagulants and the complement inhibitor eculizumab. The addition to standard treatment of pleiotropic agents such as hydroxychloroquine, statins and vitamin D could allow better disease control. Summary The lively and intense research in the APS field opens new frontiers in aPL pathogenic mechanisms, as well as diagnosis and treatment of the syndrome. Video abstract http://links.lww.com/COR/A26
Endothelium activation in the anti-phospholipid syndrome
No full textAnti-phospholipid syndrome is an autoimmune systemic disease characterized by the persistent presence of anti-phospholipid antibodies and by the occurrence of thrombosis, fetal loss and thrombocytopenia. Anti-phospholipid antibodies are widely accepted as pathogenic antibodies mainly directed against the phospholipid-binding protein beta 2 glycoprotein I. Beta 2 glycoprotein I can be expressed on the endothelial cell membranes of different anatomical localizations and recognized by the autoantibodies. The antibody binding might induce an endothelial activation both in vitro and in vivo experimental models, that was suggested to represent one of the pathogenic mechanisms leading to the prothrombotic state of the syndrome. Beta 2 glycoprotein I endothelial adhesion was found to take place through the interaction of the cationic phospholipid binding site of the molecule with anionic endothelial structures and through annexin II, the endothelial cell receptor for tissue plasminogen activator. Anti-beta 2 glycoprotein I antibodies can directly activate the cells via NF-kB translocation and the signaling cascade triggered by toll like receptors. It has been suggested that beta 2 glycoprotein I might be associated with toll like receptors because of its molecular mimicry with bacterial structures, the natural ligands of toll like receptors. The binding of the antibodies is thought to cross-link beta 2 glycoprotein I and the toll like receptors, eventually switching their signaling pathway
Pathogenesis of antiphospholipid syndrome : understanding the antibodies
No full textAntiphospholipid antibodies (aPL) are both diagnostic markers for, and pathogenic drivers of, antiphospholipid syndrome (APS). Although the presence of aPL is a necessary pre-condition, APS-associated clotting is seemingly triggered by an additional 'second hit', frequently related to innate inflammatory immune responses. beta(2) glycoprotein I (beta(2)GPI)-dependent aPL, the most important subset of these antibodies, mediate several-not necessarily alternative-thrombogenic mechanisms, mainly on the basis of their reactivity with beta(2)GPI expressed on the membrane of cells that participate in the coagulation cascade. Recurrent pregnancy complications associated with aPL cannot be explained solely by thrombosis, and alternative pathogenic mechanisms have been reported. Although one in vivo model of fetal loss suggests a mechanism of aPL-mediated acute placental inflammation, other models and the histopathological examination of APS placentae do not support a widespread inflammatory signature. beta(2)GPI-dependent aPL are thought to recognize their antigen on placental tissues, inhibit the growth and differentiation of trophoblasts, and eventually cause defective placentation. Why antibodies with similar antigen specificity produce different clinical manifestations is not clear. Characterization of the molecular basis of the pathogenic mechanisms involved, including the putative second hits and the role of complement activation, might offer an answer to this question
Primary Antiphospholipid Syndrome Patients Display Increased Levels of Cell-Bound C4d in Comparison to SLE and Healthy Donors
No full textRole of anti-beta(2) glycoprotein I antibodies in anti phospholipid syndrome : In vitro and in vivo studies
No full textAntiphospholipid syndrome (APS) is characterized by the presence of recurrent venous/ arterial thrombosis and fetal losses associated with a family of auto-antibodies directed against phospholipid (PL)-binding proteins. Among them, β2 glycoprotein I (β2GPI) is the most important. As a plasma cationic protein, β2GPI binds to anionic PLs involved in several fluid-phase coagulation steps, and more importantly, it can be expressed on the surface of different cell types. Anti-β2GPI antibodies recognize the molecule expressed on endothelial cells, platelets, monocytes, and trophoblast cells. Once bound, the antibodies trigger in vitro cell signaling that modulates biological responses potentially responsible for pathogenic mechanisms. Experimental animal models have supported the in vivo pathogenic role of anti-β2GPI antibodies in both thrombosis and fetal loss models
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