Antiphospholipid antibodies: laboratory and pathogenetic aspects

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.