AUTOANTIBODIES TO PHOSPHOLIPID-BINDING PLASMA-PROTEINS IN PATIENTS WITH THROMBOSIS AND PHOSPHOLIPID-REACTIVE ANTIBODIES

Anti-phospholipid (aPL) antibodies are defined as antibodies detected in systems employing phospholipids (PL). This general definition is mi sleading as it comprises a large group of autoimmune phospholipid-reac tive antibodies that are directed against specific phospholipid-bindin g plasma proteins, such as beta(2)-glycoprotein I (beta(2)GPI) and pro thrombin. Definition of phospholipid-reacting antibodies according to the plasma protein against which they are directed appears more approp riate and could be useful in understanding clinical events and pathoge nic mechanisms. Using ELISA systems we have studied the presence of an tibodies directed against specific phospholipid-binding proteins in a series of 22 patients with thrombosis and phospholipid-reactive antibo dies of the IgG isotype. High levels of anti-beta(2)GPI IgG were detec ted in all 22 patients. Normal values were calculated on the basis of OD values at 405 nm (OD405) obtained for 22 age- and sex-matched healt hy subjects (cut off value = 0.401). Levels of anti-beta(2)GPI antibod ies were linearly correlated with those of cardiolipin-reactive (aCL) antibodies. Eleven out of 22 patients (50%) had values of anti-prothro mbin antibodies exceeding the cut-off value of 0.250. No relationship was found between the levels of anti-beta(2)GPI and anti-prothrombin a ntibodies. Tests for antibodies against two natural inhibitors of bloo d coagulation, protein C and protein S, revealed elevated levels of an ti-protein C IgG and anti-protein S IgG in 4 and 12 patients, respecti vely. A highly significant correlation between anti-protein C IgG and anti-protein S IgG values as well as between antibody titers against t he two studied natural coagulation inhibitors and anti-prothrombin IgG was found. When comparing patients positive for aCL and presence or a bsence of a previous thrombotic episode (aCL+/T+ vs aCL+/T-), the posi tivity of anti-beta(2)GPI IgG was found to be statistically associated with thrombosis. Conversely, among patients with previous thromboembo lism with or without aCL (aCL+/T+ vs aCL-/T+) the positivity of anti-b eta(2)GPI IgG was strictly associated with the positivity of aCL, thus identifying the aPL antibody syndrome. These data demonstrate that an ti-beta(2)GPI antibodies are a marker of ''autoimmune'' thrombosis. An ti-prothrombin antibodies are not a marker of thrombosis and are close ly associated with antibodies to protein C and protein S.