Correlation between the potency of a beta2-glycoprotein I-dependent lupus anticoagulant and the level of resistance to activated protein C.
The antiphospholipid 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 (beta2-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 beta2-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 beta2-GPI-dependent LAC also showed increased APC resistance. In contrast, only one of the 11 plasma samples with a beta2-GPI-independent LAC displayed increased APC resistance. In addition, a monoclonal antibeta2-GPI antibody and patient-purified immunoglobulin G (both with LAC activity) were diluted in plasma with/without protein C. Both antibodies only displayed a beta2-GPI-dependent LAC in plasma in the presence of protein C. This indicates that the principle of the beta2-GPI LAC-assay was based on increased resistance against protein C. Surface plasmon resonance analysis was used to investigate binding between APC and beta2-GPI. We observed that beta2-GPI was able to bind APC directly, especially in the presence of a monoclonal antibeta2-GPI antibody. In conclusion, our observations show a direct correlation between a major clinical symptom of antiphospholipid syndrome (thrombosis), a diagnostic assay (beta2-GPI-dependent LAC) and a potential mechanism responsible for thrombosis in the antiphospholipid syndrome (increased APC resistance).
de Laat
Bas
B
Department of Blood Coagulation, Diagnostic Services Sanquin, The Netherlands. b.delaat@sanquin.nl
Eckmann
Carel M
CM
van Schagen
Marlies
M
Meijer
Alexander B
AB
Mertens
Koen
K
van Mourik
Jan A
JA
D020016:Activated Protein C Resistance / Q000150:complications* / Q000209:etiology* / Q000276:immunology; D017152:Antibodies, Antiphospholipid; D016736:Antiphospholipid Syndrome / Q000150:complications*; D001777:Blood Coagulation; D006801:Humans; D016682:Lupus Coagulation Inhibitor / Q000502:physiology*; D011485:Protein Binding; D011486:Protein C / Q000378:metabolism; D013927:Thrombosis / Q000209:etiology; D053482:beta 2-Glycoprotein I / Q000276:immunology* / Q000378:metabolism
D017152:Antibodies, Antiphospholipid; D016682:Lupus Coagulation Inhibitor; D011486:Protein C; D053482:beta 2-Glycoprotein I