Correlation between the potency of a beta2-glycoprotein I-dependent lupus anticoagulant and the level of resistance to activated protein C

The anti phospholipid syndrome is characterized by the occurrence of vascular thrombosis combined with the presence of antiphospholipid antibodies in plasma of patients. It has been published that antibeta2-glycoprotein I (beta(2)-GPI) antibodies, with lupus anticoagulant activity (LAC), highly correlate with thrombosis. Resistance related to antiphospholipid antibodies against activated protein C (APC) is one of the proposed mechanisms responsible for thrombosis. We investigated a possible correlation between a beta(2)-GPI-dependent LAC (titration of cardiolipin into an activated partial thromboplastin time-based assay) and increased APC resistance in a population of 22 plasma samples with LAC activity. Eleven plasma samples that displayed a beta(2)-GPI-dependent LAC also showed increased APC resistance. In contrast, only one of the 11 plasma samples with a beta(2)-GPI-independent LAC displayed increased APC resistance. In addition, a monoclonal antibeta(2)-GPI antibody and patient-purified immunoglobulin G (both with LAC activity) were diluted in plasma with/without protein C. Both antibodies only displayed a beta(2)-GPI-dependent LAC in plasma in the presence of protein C. This indicates that the principle of the beta(2)-GPI LAC-assay was based on increased resistance against protein C. Surface plasmon resonance analysis was used to investigate binding between APC and beta(2)-GPI. We observed that beta(2)-GPI was able to bind APC directly, especially in the presence of a monoclonal aritibeta(2)-GPI antibody. In conclusion, our observations show a direct correlation between a major clinical symptom of antiphospholipid syndrome (thrombosis), a diagnostic assay (beta(2)-GPI-dependent LAC) and a potential mechanism responsible for thrombosis in the antiphospholipid syndrome (increased APC resistance). Blood Coagul Fibrinolysis 19:757 - 764 (C) 2008 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.