Antiphospholipid syndrome in 2014: more clinical manifestations, novel pathogenic players and emerging biomarkers

Abstract

The clinical spectrum of the anti-phospholipid syndrome (APS) is not limited to vascular thrombosis or miscarriages but includes additional manifestations that cannot be explained solely by a thrombophilic state. Anti-cardiolipin, anti-beta2 glycoprotein I (anti-β2GPI) and lupus anticoagulant (LA) assays are not only the formal diagnostic and classification laboratory tools but also parameters to stratify the risk to develop the clinical manifestations of the syndrome. In particular, anti-β2GPI antibodies reacting with an immunodominant epitope on domain I of the molecule were reported as the prevalent specificity in APS patients, correlating with a more aggressive clinical picture. Several laboratory assays to improve the diagnostic and predictive power of the standard tests have been proposed. Plates coated with the phosphatidylserine-prothrombin complex for detecting antibodies represent a promising laboratory tool correlating with LA and with clinical manifestations. Anti-phospholipid antibodies can be found in patients with full-blown APS, in those with thrombotic events or obstetric complications only or in asymptomatic carriers. An inflammatory second hit is required to increase the presence of β2GPI in vascular tissues, eventually triggering thrombosis. Post-transcriptional modifications of circulating β2GPI, different epitope specificities or diverse anti-β2GPI antibody-induced cell signaling have all been suggested to affect the clinical manifestations and/or to modulate their occurrence.

Antiphospholipid and antioangiogenic activity in females with recurrent miscarriage and antiphospholipid syndrome

“…Our results particularly associate the presence of LA and/or a-β2GP1 Abs, but not that of ACA, with recurrent miscarriage. According to Meroni et al [7], patients with APS should be divided in four categories: category I includes women with more than one positive test in any combination, and category II includes those women with only one positive test Our results show a similar behaviour, since group M bears a higher number of positive biomarkers than group NM. However, some women with persistent elevated levels of ACA and LA and history of thrombotic events do not have fetal complications while, in some cases, women without ACA or LA and without a known cause, undergo recurrent miscarriage.…”

“…Although placental thrombotic events may play an important role [3], it is nowadays assumed that non-thrombotic mechanisms would be the main cause for the defective placentation observed in patients with antiphospholipid syndrome (APS) [4][5][6]. APS is an autoimmune disease characterized by arterial/venous thrombosis and/or obstetric complications, associated to the persistent presence of anticardiolipins (ACA) and/or lupus anticoagulant (LA) and/or anti-2 glycoprotein 1(a-2GP1) [7]. APS is either a primary disease or it can be associated to another autoimmune disease, such as systemic lupus erythematosus (SLE).…”

Can we withdraw anticoagulation in patients with antiphospholipid syndrome after seroconvertion?

“…However, anti-vimentin antibodies have been found in a wide panel of systemic autoimmune diseases in addition to APS, raising the question of their specificity [55].…”

Obstetric Antiphospholipid Syndrome: Lobsters Only? Or Should We Also Look for Selected Red Herrings?

“…The definition of each clinical outcome should be stringent; causes of pregnancy morbidity other than aPL should be carefully excluded; a large (it is hoped) sample size should allow assessing for the first time each outcome individually. This study should also envisage testing for antibodies against domain I of β 2 -GPI, phosphatidylserine/prothrombin complex, and phosphatidylethanolamine: These novel diagnostic and prognostic tools should lead to more accurate serological risk stratification 21 .…”