SP0176 PATHOGENIC ANTIBODIES IN PHOSPHOLIPID SYNDROM

Abstract

Antiphospholipid syndrome (APS) is prothrombotic systemic autoimmune disorder characterized with multisystem manifestation, most commonly venous and arterial thromboembolism and/or recurrent pregnancy loss. The varying clinical phenotype is associated with heterogeneity in the pathogenic antiphospholipid antibodies (aPL) that are central to the diagnosis of APS. According to the international consensus statement on classification criteria, APS is classified when persistently elevated levels of specific aPL, such as lupus anticoagulant (LA), anti-cardiolipin (aCL) and anti-β2 glycoprotein I (anti-β2GPI) antibodies, are confirmed in addition to clinical manifestations (1, 2). The exact pathogenesis of APS is unknown, but aPL have been described to activate monocytes, neutrophils, dendritic cells and placental tissue (3). Despite the fact that many different proteins have been identified as being involved in the pathogenesis of APS, accumulating evidence from in vitro experiments as well as animal studies has revealed that β2GPI is the main target for aPL. It was also shown that triple aPL positivity, defined by detection LA, high titres of aCL and anti-β2GPI antibodies, correlates better with both thrombosis and pregnancy morbidity than any other aPL profile (4). Several autoantibodies outside those included in APS classification criteria could be also relevant to APS pathogenesis (5) and therefore, antibodies against other antigen targets have been investigated. Current evidence shows that some of these antibodies, particularly antibodies against domain I of β2GPI (anti-DI-β2GPI) and phosphatidylserine dependent anti-prothrombin antibodies (aPS/PT) might be relevant in the better recognition of APS patients. These antibodies are commonly referred as non-criteria aPL (6) because they have not been yet accepted as laboratory criterion for the diagnosis of APS. The DI of β2GPI has been identified as the most relevant antigenic target involved in β2GPI/anti-β2GPI antibody binding. Anti-DI-β2GPI antibodies were found to be strongly related to thrombosis and pregnancy complication and are more frequently detected in patients with APS than in asymptomatic aPL carriers (7). High titres of anti-DI-β2GPI are also frequently present in triple aPL positive patients. Nevertheless, it is far too soon to recommend replacement of anti-β2GPI testing with an anti-DI-β2GPI antibody assay because it was shown that about 30% of patients with anti-β2GPI antibodies are negative for anti-DI-β2GPI antibodies (8). The clinical significance of autoantibodies reacting with epitopes other than DI was also investigated in multicenter study (9). The results showed a diverse clinical association with reactivity to different epitopes on β2GPI, suggesting all domains were relevant. Therefore, more detailed profiling of domain specificity and avidity of anti-β2GPI antibodies may be useful as risk stratification for clinical events. aPS/PT antibodies also represent strong risk factor for thrombosis. Results of multicenter study demonstrated that IgG aPS/PT detection might contribute to a better and more reliable identification of APS patients (10). Due to the heterogeneity of aPL (criteria and non-criteria) the interpretation of aPL results is huge challenge in daily routine practice and should always be related to clinical symptoms and therefore, interaction between the laboratory and clinician is essential.