Antiphospholipid Antibodies: Laboratory and Pathogenetic Aspects

Abstract

Antiphospholipid antibodies (aPL) constitute a heterogeneous group of autoantibodies that share the ability to bind phospholipids (PL) alone, protein-PL complexes, or PL-binding proteins. They have been detected in isolation, in association with autoimmune diseases such as systemic lupus erythematosus (SLE), and during the course of different infections. aPL have been associated with an array of clinical manifestations in virtually every organ, although deep vein and arterial thrombosis as well as pregnancy morbidity are predominant. The co-occurrence of these clinical findings with aPL constitutes the so-called antiphospholipid syndrome (APS). aPL can be detected by immunological methods [e.g., anticardiolipin antibodies (aCL)] or by functional methods that exploit the effect of aPL on blood coagulation [lupus anticoagulant (LA)]. Since aPL are heterogeneous, numerous immunological and coagulation assays have been developed. These assays have not been fully standardized, and, therefore, problems such as high interlaboratory variation are relatively frequent. Recently, recommendations have been published regarding LA and aCL testing. Not all aPL are pathogenic. However, when they are not associated with infections, they have a role in the pathogenesis of APS. Clinical and experimental data have shown that aPL exert their pathogenic activity by interfering with the function of coagulation factors, such as thrombin and factors X, XI and XII, and with the function of anticoagulant proteins of the protein C system. In addition, aPL interaction with platelets and endothelial cells induces a pro-adhesive activated phenotype.

IgG glycan hydrolysis by endoglycosidase S diminishes the proinflammatory properties of immune complexes from patients with systemic lupus erythematosus: A possible new treatment?

“…It is well established that ICs are involved in many of the disease manifestations of SLE, including nephritis (3,5), pleuritis (6), vasculitis (7), skin and CNS involvement (8)(9)(10), and thrombosis (11,12). Deposited IgG or ICs cause local inflammation by activation of the classical pathway of complement with recruitment of PMNs, which could contribute to tissue destruction.…”

“…Many of the disease manifestations of SLE, including nephritis (3,5), pleuritis (6), vasculitis (7), and skin and central nervous system (CNS) involvement (8)(9)(10) are most likely IC mediated. Furthermore, autoantibodies against phospholipids are associated with the development of thrombosis (11,12). If not deposited in tissue, ICs may be phagocytosed by plasmacytoid dendritic cells (PDCs) and induce the production of IFN␣ (13,14), which is a key cytokine in the development and progression of SLE (15) and breaking of self tolerance leading to autoimmunity (16)(17)(18).…”

A novel mechanism of thrombosis in antiphospholipid antibody syndrome

“…On the contrary, Bowie et al in 1963 described the association of this anti-coagulant factor with thrombosis [9] and ten years later Feinstein and Rapaport used the term LA for this in vitro coagulation inhibitor [10]. However LA proved to be a misnomer because it induces thrombosis in vivo and also occurs in a variety of conditions unrelated to SLE, in other autoimmune disorders, and in patients receiving drugs such as procainamide and chloropromazine, in children with recent acute viral infections, in patients with HIV infection and in patients with unexplained venous or arterial thrombosis [1]. Subsequently, chronic false positive tests for syphilis were associated with arterial thrombosis and thrombocytopenia [11], while LA and aPL were associated with recurrent abortions [12].…”

“…The conversion of plasminogen to plasmin is enhanced by two immunologically distinct, physiologic plasminogen activators: tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA). Inhibition of the fibrinolytic system may occur at the level of the plasminogen activators by specific plasminogen activator inhibitors (PAI-1 and PAI-2) or at the level of plasmin, by a2-antiplasmin [1].…”

“…Antiphospholipid Antibody Syndrome (APS) is an autoantibodymediated acquired thrombophilia characterized by recurrent arterial or venous thromboses and/or pregnancy morbidity, accompanied by antiphospholipid (aPL) antibodies [1]. Although aPL antibodies were originally thought to recognize negatively charged phospholipids (PLs), it became evident that they recognize in fact phospholipidbinding plasma proteins, mainly a plasma apolipoprotein known as b2-glycoprotein I (b2GPI) [2] and prothrombin [3].…”