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Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán

2005, Number 4

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Rev Invest Clin 2005; 57 (4)

Activated protein C resistance and lupus anticoagulant activity induced by plasma and purified monospecific human IgG anti-Β2-glycoprotein-I antibodies

Viveros ME, Cabiedes J, Reyes E, Cabral AR

Language: English
References: 54
Page: 563-571
PDF size: 104.52 Kb.


ABSTRACT

Introduction. We investigated the activated protein C resistance (APCR) phenotype and the lupus anticoagulant (LA), activity induced by anti-Β2-glycoprotein-I (anti-Β2GP-I) antibodies. Patients and methods. We studied plasma and sera samples from 29 patients with persistently positive anti-Β2GP-I: 22 with thrombosis (12 with primary APS, 10 with APS secondary to SLE) and seven without thrombosis (all with SLE); 25 healthy subjects were studied as controls. We detected anticardiolipin antibodies (ACA); IgG (and its subclasses) and IgM anti-Β2GP-I, on irradiated and non-irradiated plates by ELISA. APCR was assessed by the activated partial thromboplastin time (APTT)-based assay and by the modified test. The FV Leiden mutation was studied by PCR. LA determination included screening and confirmatory dRVVT. Serum anti-Β2GP-I were affinity purified on sepharose columns and their isotype, subclass, and reactivity against various antigens were studied by ELISA. Results. We found that titers of IgG anti-Β2GP-I on irradiated plates were higher than on non-irradiated plates (p = 0.002), IgG2 was the predominant subclass. Fifteen patients (13 with thrombosis) had LA and 15 (also 13 with thrombosis) induced the APCR phenotype. Eleven (all with thrombosis) had both. Two patients were heterozygous for the Leiden mutation. Two purified antibodies, monospecific for Β2GP-I, induced an in vitro APCR phenotype and LA activity. Conclusions. Our results seem to indicate that the inhibition of the APC anticoagulant function by IgG2 anti-Β2GP-I with LA activity may be one of the responsible mechanisms of thrombophilia in patients with APS.


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