Antiprothombin antibodies and the diagnosis of antiphospholipid syndrome
Section snippets
Markers for the diagnosis of antiphospholipid syndrome
Antiphospholipid syndrome (APS) is a clinical condition characterized by recurrent thrombotic events/pregnancy morbidity associated to the persistence of antiphospholipid antibodies (aPL).
Antiphospholipid antibodies are classically classified according to their in vitro method of detection in anticardiolipin antibodies (aCL) measured by enzyme-immunosorbent assay (ELISA) and lupus anticoagulant (LA) detected by clotting assays. However, the current concept of aPL includes antibodies directed
Prothrombin structure and in vitro function of antiprothrombin antibodies
Prothrombin (factor II) is a vitamin K-dependent glycoprotein present at a concentration of approximately 100 μg/ml in normal plasma. Mature human prothrombin consists of a single-chain glycoprotein with a molecular weight of 72 kDa [17]. During its biosynthesis in the liver, prothrombin undergoes γ-carboxylation. These γ-carboxyglutamic residues, known as the Gla-domain, are located on fragment 1 of the prothrombin molecule. Gla-domain is essential for the calcium-dependent binding of
Detection methods and clinical associations of antiprothrombin antibodies
Double diffusion, counterimmunoelectrophoresis [21], [22], [23], and assays based on the impairment of prothrombin activation by aPT were the first techniques used for screening aPT [15], [24], but they were not suitable for the routine clinical practice.
In 1995, Arvieux et al. [25] described an ELISA for detection of aPT using prothrombin as antigen coated onto irradiated plates (aPT-A). Since then, some clinical studies have investigated their clinical implications [26]. Some of these studies
Lupus anticoagulant determination and antiprothrombin antibodies
LA is detected by functional assays according to the recommendation of the Scientific and Standardisation Committee of the International Society of Thrombosis and Haemostasis [48]. A tree-step approach has been proposed:
- (1)
Screening test to evaluate if phospholipid-dependent coagulation test are prolonged,
- (2)
Mixing test to demonstrate that the prolongation of the clotting time is caused by an inhibitor present in plasma,
- (3)
Confirmation of the phospholipid-nature of the inhibitory antibody by adding
Antiphospholipid antibodies specificity and the risk of thrombosis
LA have been reported to represent a stronger risk factor for thrombosis than aCL [51], [52] or aPT [36] based on the higher relative risk of thrombotic events. Autoimmune thrombosis and pregnancy morbidity is caused by, or at least correlated with, a group of autoantibodies with similar properties that affect the phospholipid-dependent reactions. The autoantigens and the detection methods are heterogeneous. The comparison between the results of functional assays that detect activity of
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Evasion and interactions of the humoral innate immune response in pathogen invasion, autoimmune disease, and cancer
2015, Clinical ImmunologyCitation Excerpt :Activation of the intrinsic pathway in coagulation occurs through activation of Factor XII specifically by preformed fibrin clots [92]. High levels of Factor XIIa-anti-thrombin (AT) complex are found in APLS and SLE patients with previous venous thrombosis and arterial thrombosis [92,93] and SLE patients have a higher risk of developing thrombosis compared with APLS [94]. Thus, multiple mechanisms alter the coagulation cascade in SLE and APLS patients.
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