Acquired activated protein C resistance associated with IgG antibodies against beta2-glycoprotein I and prothrombin as a strong risk factor for venous thromboembolism.

Abstract

BACKGROUND:

Venous thromboembolic events such as deep vein thrombosis and pulmonary embolism are common manifestations of antiphospholipid syndrome. Our aim was to clarify the roles of anti-phospholipid (aPL) antibodies in the pathogenesis of venous thromboembolism (VTE) in patients with systemic lupus erythematosus (SLE).

METHODS AND RESULTS:

We examined anti-cardiolipin/beta2-glycoprotein I (anti-CL/beta2-GPI) antibody concentrations, anti-phosphatidylserine/prothrombin (anti-PS/PT) antibody concentrations, and lupus anticoagulant (LA) activity in 87 patients with SLE (21 with VTE and 66 without thrombosis). Both anti-CL/beta2-GPI and anti-PS/PT antibodies strongly correlated with LA activity. Multivariate logistic analysis confirmed that both anti-CL/beta2-GPI and anti-PS/PT antibodies were significant independent risk factors for VTE (odds ratios = 4.98 and 7.54, respectively; 95% confidence intervals, 1.51-16.4 and 2.30-24.7, respectively). We therefore studied the in vitro effects of IgG fractions containing anti-CL/beta2-GPI or anti-PS/PT antibodies on the anticoagulant activity of activated protein C (APC) and found that purified IgG containing anti-CL/beta2-GPI or anti-PS/PT antibodies significantly hampered the anticoagulant activity of APC. We also studied the ability of IgG fractions to impede the anticoagulant activity of APC before and after complete removal of anti-CL/beta2-GPI or anti-PS/PT antibodies by adsorption. Removal of anti-CL/beta2-GPI or anti-PS/PT antibodies from all positive IgG samples clearly decreased the inhibitory effect of those samples on APC anticoagulant activity.

CONCLUSIONS:

Anti-CL/beta2-GPI and anti-PS/PT antibodies independently cause APC resistance, which may contribute to risk of VTE in patients with SLE.

• Authors: Junzo Nojima, Hirohiko Kuratsune, Etsuji Suehisa, Yoshinori Iwatani, Yuzuru Kanakura
• Journal: Clinical chemistry (Clin Chem) Vol. 51 Issue 3 Pg. 545-52 (Mar 2005) ISSN: 0009-9147 [Print] England
• PMID: 15637132 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Antiphospholipid
• Cardiolipins
• Glycoproteins
• Immunoglobulin G
• Phosphatidylserines
• Protein C
• beta 2-Glycoprotein I
• Prothrombin

Topics

• Activated Protein C Resistance (etiology, immunology)
• Adult
• Antibodies, Antiphospholipid (blood)
• Antiphospholipid Syndrome (etiology, immunology)
• Cardiolipins (immunology)
• Enzyme-Linked Immunosorbent Assay
• Female
• Glycoproteins (immunology)
• Humans
• Immunoglobulin G (blood)
• In Vitro Techniques
• Lupus Erythematosus, Systemic (complications)
• Male
• Middle Aged
• Multivariate Analysis
• Partial Thromboplastin Time
• Phosphatidylserines (immunology)
• Protein C (analysis)
• Prothrombin (immunology)
• Risk Factors
• Thromboembolism (etiology, immunology)
• Venous Thrombosis (etiology, immunology)
• beta 2-Glycoprotein I