ABSTRACT
The presence of antiphospholipid antibodies in plasma is a risk factor for thrombo-embolic complications. In vitro, however, the same antibodies can prolong clotting times in coagulation assays, a classic marker for a bleeding tendency. For years this contradiction puzzles many scientists.We now know that the term antiphospholipid antibodies comprises a heterogeneous population of antibodies and there is growing evidence that only subpopulations of antiphospholipid antibodies are relevant for the clinical complication. In combination with new information on the complex interaction between antiphospholipid antibodies, the protein beta2-Glycoprotein I, and cellular surfaces have opened new avenues for the understanding of the pathology of this syndrome.
Subject(s)
Antibodies, Antiphospholipid/immunology , Glycoproteins/physiology , Receptors, LDL/physiology , Animals , Antibodies, Antiphospholipid/blood , Antibodies, Antiphospholipid/chemistry , Humans , Models, Biological , Platelet Activation , Receptors, LDL/immunology , Thromboembolism/pathology , beta 2-Glycoprotein IABSTRACT
From its discovery in the early 60s till the beginning of the 90s, there was not much interest in plasma protein beta2-glycoprotein I (beta2-GPI). The finding that beta2-GPI acts as an essential cofactor for the detection of antiphospholipid antibodies (aPL) tremendously increased the interest in beta2-GPI [Lancet 335 (1990) 1544; Lancet 336 (1990) 177; Proc. Natl. Acad. Sci. U. S. A. 87 (1990) 4120]. It is now generally accepted that autoantibodies directed towards beta2-GPI are not only a serological marker but that they are involved in the pathology of the antiphospholipid syndrome (APS). In this review, we will first discuss the biochemistry of the protein beta2-GPI and the influence that the antibodies have on the function of beta2-GPI. Next, we will discuss the problems that are faced when assays to detect the presence of the autoantibodies are performed, emphasizing the urgent need for standardization of the anti-beta2-GPI-ELISA. Finally, we will discuss our latest insights into beta2-GPI and its role in the pathology of APS. Thereby, we will focus on the role of dimerized beta2-GPI on platelet and endothelial cell function.