β2-Glycoprotein I, the playmaker of the antiphospholipid syndrome

From its discovery in the early 60s till the beginning of the 90s, there was not much interest in plasma protein β2-glycoprotein I (β2-GPI). The finding that β2-GPI acts as an essential cofactor for the detection of antiphospholipid antibodies (aPL) tremendously increased the interest in β2-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 β2-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 β2-GPI and the influence that the antibodies have on the function of β2-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-β2-GPI-ELISA. Finally, we will discuss our latest insights into β2-GPI and its role in the pathology of APS. Thereby, we will focus on the role of dimerized β2-GPI on platelet and endothelial cell function.