Abstract
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.
Highlights
The anti-phospholipid antibodies were first described in the early 80s in patients with systemic lupus erythematosus (SLE), being only later recognized as serological markers of a distinct clinical entity, the anti-phospholipid syndrome (APS)
Most of the studies addressing the clinical significance of anti-Domain I (DI) antibodies in APS patients focused on the association with thrombosis, since the results presented by De Laat et al in 2005
It is well ascertained that anti-β2GPI antibodies may target multiple epitopes in the same molecule; basic research as well as clinical studies focused on anti-DI and anti-DIV/V antibodies
Summary
The anti-phospholipid antibodies (aPL) were first described in the early 80s in patients with systemic lupus erythematosus (SLE), being only later recognized as serological markers of a distinct clinical entity, the anti-phospholipid syndrome (APS). Multiple epitopes in the β2GPI can be bound by anti-β2GPI antibodies, even autoantibodies purified from a given patient may react against several epitopes in the same molecule. Such phenomenon might be secondary to an intramolecular epitope spreading, that may occur following initiation of the immune response by a single epitope in the β2GPI molecule. A particular epitope in a positively charged discontinuous structure located in the N-terminal β2GPI named domain (D) I has been identified as the most relevant antigenic target involved in β2GPI/anti- β2GPI antibody binding among APS patients [3]. It is very relevant from a clinical point of view to understand whether the domain specificities of anti-β2GPI antibodies are distributed in patients with SLE
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