<b>Aim:</b> To determine the zones of B2GP1 recognized by antibodies of IgA isotype from patients with APS symptomatology and positive for IgA anti-B2GP1.
β2-glycoprotein I/anti-β2-glycoprotein I antibody complex (β2/aβ2) could promote oxLDL-induced endothelial inflammation through Toll-like receptor 4 (TLR4), therefore accelerates atherosclerosis in patients with anti-phospholipid syndrome (APS).
A1-A1 binds to β2GPI/antibody complexes, preventing their association with ApoER2 and anionic phospholipids, and reducing thrombus size in the mouse model of APS.
All variants were able to inhibit APS-IgG from: binding to whole β2GPI in ELISA, altering the clotting properties of human plasma and promoting thrombosis and tissue factor expression in mice.
Antiphospholipid antibodies (aPL), particularly against the phospholipid binding protein beta-2 glycoprotein I (β2GPI), play an important role in APS pathological mechanisms. aPL can activate intracellular signal transduction in a β2GPI-dependent manner to induce inflammatory responses, and promote hypercoagulable state and recurrent spontaneous abortion when β2GPI is associated with the cell surface receptor.
At least one clinical (vascular thrombosis or pregnancy morbidity) and one lab-based (positive test result for lupus anticoagulant, anticardiolipin antibodies and/or anti-β2-glycoprotein 1 antibodies) criterion have to be met for a patient to be classified as having APS.
Background and Purpose- International classification criteria for antiphospholipid syndrome (APS) include IgM (immunoglobulin M), aCL (anticardiolipin), and aB2GPI (anti-β2-glycoprotein-I) antibodies, but their relevance is still debated.
Background There is general consensus that the antiphospholipid syndrome (APS) is caused by antiphospholipid antibodies (aPL) with antibodies against β2-glycoprotein-I being the most relevant. aPL that bind phospholipids in the absence of protein cofactors are generally considered pathogenetically irrelevant.
Domain I (DI) of human beta 2 glycoprotein I (beta2GPI) is thought to contain crucial antibody binding epitopes for antiphospholipid antibodies (aPL), which are critical to the pathogenesis of APS.
Genetic studies of beta(2)-glycoprotein-1(GP1) polymorphisms have been determined and valine/leucine polymorphism could be a genetic risk for having anti-beta(2)-GP1 antibodies and APS.
Genetic studies of a representative antigen, beta2-glycoprotein-I (beta(2)GPI), have been carried-out and a particular valine(247)/leucine polymorphism could be a genetic risk for presenting anti-beta(2)GPI antibodies and APS.
Glycosylation of B2GP1 can impact auto antibody recognition leading to the development of antiphospholipid syndrome (APS), which can result in miscarriages or thrombosis.
HETE-PLs enhanced membrane binding of the serum protein β2GP1 (β2-glycoprotein 1), an event considered central to the autoimmune reactivity responsible for APS symptoms.
IgG and IgM antibodies directed at β2-glycoprotein I are included in the classification criteria for the antiphospholipid syndrome (APS) while the IgA antibodies against β2-glycoprotein I (IgA aβ2GPI) are not.
In antiphospholipid syndrome (APS), antiphospholipid antibodies (aPL) binding to β2 glycoprotein I (β2GPI) induce endothelial cell-leukocyte adhesion and thrombus formation via unknown mechanisms.
In Asian-Indian patients with suspected APS, aPSPT outperformed all classical APLs in diagnosis/classification of obstetric APS and both isotypes of beta 2-glycoprotein-I antibodies in diagnosis/classification of APS. aPSPT could reclassify additional 12.1 and 42.8% patients as APS overall and obstetric APS respectively, over and above the cases satisfying revised Sapporo criteria.
In conclusion, anti-β2GPI aPL activate platelets while co-factor-independent anticardiolipin aPL have no effect. mTOR is involved in this signaling process which has implications beyond APS, because so far the role of mTOR signaling in platelets is incompletely explored and requires further study.
In most cases, the epitopes targeted by autoreactive β2GPI-reactive CD4 T cells in APS and SLE appear to arise as a consequence of antigenic processing of β2GPI that is structurally different from the soluble native form.
In the antiphospholipid syndrome (APS), pathogenic antiphospholipid antibodies (aPL) that cause thrombosis or pregnancy morbidity are characterized by binding to anionic phospholipids (PL) and beta2-glycoprotein I (beta(2)GPI).
In the antiphospholipid syndrome (APS), antiphospholipid antibody (aPL) recognition of β2 glycoprotein I promotes thrombosis, and preclinical studies indicate that this is due to endothelial nitric oxide synthase (eNOS) antagonism via apolipoprotein E receptor 2 (apoER2)-dependent processes.