<<Antiphospholipid>> antibodies (aPL) are a heterogenous group of auto
antibodies with clinical importance because of their association with
thrombotic events, both venous and arterial. Traditionally, aPL have b
een assayed using phospholipid-dependent tests and are classified as l
upus anticoagulants and anticardiolipin antibodies (ACA), based on the
method of detection. Most antibodies associated with the aPL syndrome
and detected in standard assays are actually directed against two pho
spholipid-binding plasma proteins, beta(2)-glycoprotein I and prothrom
bin. These antibodies can also be detected in immunoassays (ELISA) uti
lizing purified protein antigens, in the absence of phospholipids. The
main advantage of beta(2)GPI-ELISA compared with conventional cardiol
ipin-ELISA appearing from initial clinical studies is greater specific
ity for the aPL syndrome, due to (i) ignorance of <<authentic>> ACA th
at interact directly with cardiolipin; (ii) detection of species speci
fic anti-beta(2)GPI antibodies poorly reactive with bovine beta(2)GPI
in the cardiolipin-ELISA. Other proteins proposed as target antigens o
f aPL are protein C, protein S, annexin V, high- and low-molecular wei
ght kininogens, the latter being involved in the binding of antibodies
to phosphatidylethanolamine. The possibility that particular autoanti
bodies (or combinations of autoantibodies) explain the observed clinic
al spectrum of the aPL syndrome is attractive, but much remains to be
learned about their pathogenicity and origin in order to improve diagn
osis and therapy.