Binding of antiphospholipid antibodies to discontinuous epitopes on domain I of human β2-glycoprotein I: Mutation studies including residues R39 to R43

Oxidation of β2-glycoprotein I associates with IgG antibodies to domain I in patients with antiphospholipid syndrome

Domain I (DI) of beta-2-glycoprotein I (β2GPI) contains the immunodominant epitope for pathogenic antiphospholipid antibodies (aPL). DI is exposed in the linear form of the molecule but not in the circular form that comprises 90% of serum β2GPI. The majority of circulating β2GPI is biochemically reduced with two free thiols in Domain V. However, increased levels of oxidised β2GPI are found in p...

Antibodies to domain I of β-2-glycoprotein I and IgA antiphospholipid antibodies in patients with ‘seronegative’ antiphospholipid syndrome

The standard serological tests included in the classification criteria for antiphospholipid syndrome (APS) are those to detect immunoglobulin G (IgG) and IgM antibodies to cardiolipin (aCL) or β-2-glycoprotein I (anti-β2GPI) and the lupus anticoagulant. It is increasingly recognised, however, that some patients have typical thrombotic and non-thrombotic features of APS but test repeatedly negat...

A novel pathway for human endothelial cell activation by antiphospholipid/anti-β2 glycoprotein I antibodies.

Antiphospholipid Abs (APLAs) are associated with thrombosis and recurrent fetal loss. These Abs are primarily directed against phospholipid-binding proteins, particularly β(2)GPI, and activate endothelial cells (ECs) in a β(2)GPI-dependent manner after binding of β(2)GPI to EC annexin A2. Because annexin A2 is not a transmembrane protein, the mechanisms of APLA/anti-β(2)GPI Ab-mediated EC activ...

Optimization of Unnicked β2-Glycoprotein I and High Avidity Anti-β2-Glycoprotein I Antibodies Isolation

Patient biological material for isolation of β2-glycoprotein I (β2GPI) and high avidity IgG anti-β2-glycoprotein I antibodies (HAv anti-β2GPI) dictates its full utilization. The aim of our study was to evaluate/improve procedures for isolation of unnicked β2GPI and HAv aβ2GPI to gain unmodified proteins in higher yields/purity. Isolation of β2GPI from plasma was a stepwise procedure combining n...

Structural Changes in β2-Glycoprotein I and the Antiphospholipid Syndrome