Activated protein C resistance and lupus anticoagulant activity induced by plasma and purified monospecific human IgG anti-beta2-glycoprotein-I antibodies. Revista de investigación clínica; organo del Hospital de Enfermedades de la Nutrición. [Rev Invest Clin] Journal article | | Title | Activated protein C resistance and lupus anticoagulant activity induced by plasma and purified monospecific human IgG anti-beta2-glycoprotein-I antibodies. | | Author(s) | Viveros ME, Cabiedes J, Reyes E, Cabral AR | | Institution | Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán. | | Source | Rev Invest Clin 2005 Jul-Aug; 57(4):563-71. | | MeSH | Activated Protein C Resistance
Adult
Aged
Antibodies, Anticardiolipin
Antibody Specificity
Antiphospholipid Syndrome
Autoantibodies
Autoantigens
Autoimmune Diseases
Enzyme-Linked Immunosorbent Assay
Factor V
Female
Glycoproteins
Humans
Immunoglobulin G
Immunoglobulin M
Lupus Coagulation Inhibitor
Lupus Erythematosus, Systemic
Male
Middle Aged
Partial Thromboplastin Time
Phenotype
Plasma
Plastics
Prothrombin Time
Research Support, Non-U.S. Gov't
Thrombophilia
Thrombosis
| | Abstract | INTRODUCTION: We investigated the activated protein C resistance (APCR) phenotype and the lupus anticoagulant (LA), activity induced by anti-beta2-glycoprotein-I (anti-beta2GP-I) antibodies.
PATIENTS AND METHODS: We studied plasma and sera samples from 29 patients with persistently positive anti-beta2GP-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-beta2GP-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-2 GP-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-beta2GP-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 beta2GP-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-beta2GP-I with LA activity may be one of the responsible mechanisms of thrombophilia in patients with APS. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 16315641 |
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