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Beta-2 glycoprotein I (β2GPI) is the main antigenic target for antiphospholipid antibodies (aPL), the serological markers of antiphospholipid syndrome (APS), a systemic autoimmune disease characterized by vascular thrombosis and/or pregnancy morbidity. aPL are detected in 20 to 50% of patients with systemic lupus erythematosus (SLE), representing a poor prognostic factor. Indeed, thrombotic events heralds high morbidity and mortality, being regarded as the strongest predictors of death in the first five years after SLE onset. It would be thus very important to identify a reliable laboratory tool such as anti-domain antibodies to better risk-stratify lupus patients according to the aPL profile, in order to tailor treatment strategies. Domain I (DI) of β2GPI has lately been identified as the main epitope targeted by antibodies reacting against β2GPI isolated from APS patients, well correlating with thrombotic as well as obstetric manifestations. Interestingly, anti-DI antibodies have been shown to well correlate with lupus anticoagulant and to predict the clinical manifestations of the syndrome, thrombotic events as well as pregnancy complications. Further, anti-DI antibodies allow to identify patients at highest clinical risk, presenting a good specificity for APS. On the other hand, anti- β2GPI antibodies from aPL asymptomatic carriers or subjects with infectious diseases preferentially display reactivity towards DIV or DV of the molecule.
Few studies have to date evaluated the domain profile of anti-β2GPI antibodies in subjects with SLE, even though it would be very relevant from a clinical point of view to understand whether among patients with SLE the domain specificities of anti-β2GPI antibodies display a clinical meaning comparable to the one they exert in APS. It is therefore rather appropriate to review the available evidence about anti-domain specificities with a particular focus on SLE.