Biochemistry of Antiphospholipid Antibodies
Antiphospholipid antibodies are a heterogeneous group of immunoglobulins (IgG, IgM and IgA) targeted against anionic phospholipids such as diphosphatidylglycerol (cardiolipin), phosphatidylserine (PS), phosphatidylinositol (PI) and phosphatidylglycerol (PG). The binding of the antibodies is dependent on the secondary structure of the phospholipids (lamellar or hexagonal structure). Recent studies have shown that some antibodies are targeted against phospholipid/protein-complexes. The protein serves as cofactor and was identified as β2-glycoprotein I. These antibodies are autoantibodies. As they target phospholipids essential for the coagulation, they influence the haemostatic balance. The mechanism of formation of these autoantibodies is not yet known. The group of antibodies is very heterogeneous.
Clinical significance of Antiphospholipid Autoantibodies and Lupus Anticoagulant
The clinical situation associated with the occurrence of antiphospholipid autoantibodies is defined as antiphospholipid antibody syndrome (APS). The symptoms include recurrent venous and arterial thromboembolic diseases, thrombocytopenia and spontaneous abortions. In the case of a primary antiphospholipid antibody syndrome, no fundamental disease can be recognized. Secondary APS is often associated with autoimmune diseases such as systemic lupus erythematosus (SLE). High antibody concentrations represent an increased risk for thromboembolic diseases. Anticardiolipin antibodies may be found in subjects with infectious diseases, especially syphilis, but these have not been correlated with the occurrence of thrombosis. These “infection-anticardiolipin-antibodies” differ from the “autoimmune anticardiolipin-antibodies”. The heterogeneity of the antibodies does not allow all antibodies to be identified with a single test. The following tests are the most commonly used:
- Coagulation test for the determination of lupus anticoagulants (LA): aPTT, dRVVT, KCT, SACT
- ELISA for the determination of e.g. anti-cardiolipin, anti-phosphatidylserine and anti-β2-Glycoprotein I-antibodies.
Clinical or Research use of Lupus anticoagulant
- Differential diagnostic in thrombophilia