Submitted April 20, 2006
Accepted August 25, 2006
Current concepts on the pathogenesis of the antiphospholipid syndrome
Bill Giannakopoulos, Freda Passam, Soheila Rahgozar, and Steven A. Krilis*
St. George Hospital, University of New South Wales, Sydney, Australia
Dept of Haematology, St. George Hospital, University of New South Wales, Sydney, Australia
* Corresponding author; email: s.krilis{at}unsw.edu.au.
The antiphospholipid syndrome (APS) is an important cause of acquired thrombophilia. It is characterised by the core clinical manifestations of thrombosis, either venous or arterial, and in women it can also be associated with recurrent fetal loss. The detection of persistently elevated levels of antiphospholipid antibodies (aPL Abs) is a requisite laboratory feature for the diagnosis to be made. The dominant antigenic targets in APS are beta 2-glycoprotein I (
2-GPI) and prothrombin. There is an accumulating body of experimental evidence which suggests that specific subgroups of aPL Abs may directly contribute to disease pathogenesis. This review critically examines the experimental evidence underlying the various propositions made to explain how these antibodies may predispose to disease in humans. Furthermore, it also examines the evidence relating to the immunological mechanisms which may contribute to the breakage of peripheral tolerance in this disorder. Delineating the strengths and limitations of the experimental evidence accumulated thus far will hopefully stimulate further experimentation towards achieving the ultimate goal of precisely defining the dominant pathogenic mechanisms operational in APS. This may pave the way for the development of improved therapies.
