Clinical significance of phospholipid-cofactor antibodies in patients with systemic lupus erythematosus-associated antiphospholipid syndrome

Shereen A Machaly,Hesham A Sharaf El-Din

doi:10.4103/1110-161x.123795

Abstract

To establish whether antibodies directed against phospholipid-binding plasma proteins such as β2-glycoprotein I (β2GPI), prothrombin (PT), and Annexin V (AnxV) constitute a risk factor for thrombosis in patients with systemic lupus erythematosus (SLE)-associated antiphospholipid syndrome (SLE/APS). A group of SLE patients (with and without APS) and patients with primary APS (PAPS) were included in this study. Fifteen patients with deep vein thrombosis but without antiphospholipid (aPL) antibodies, and another 15 age-matched and sex-matched apparently healthy individuals served as a control group. All patients were investigated for lupus anticoagulants and detection of anticardiolipin (aCL) immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies. Antibodies against β2GPI (IgG and IgM), PT (IgG and IgM), and AnxV (IgG) were also measured using the respective enzyme-linked immunosorbent assays. The study included 58 SLE patients (18 SLE/APS patients and 40 patients without APS) as well as 40 patients with PAPS, mean age 43 years (range: 18–74 years). IgG and/or IgM aCL antibodies were detected in all patients with PAPS (100%), whereas the prevalence rates of aPL-cofactor antibodies were as follows: 75% anti-β2GPI, 70% anti-PT, and 25% anti-AnxV antibodies. In SLE patients without APS, aCL antibodies were detected in 17.5%, anti-β2GPI antibodies in 20%, anti-AnxV antibodies in 20%, and anti-PT antibodies in 10% of patients. None of the antibodies measured were detected in deep vein thrombosis cases or healthy controls. Measurement of antiphospholipid-cofactor antibodies in addition to the more widely used aCL and anti-β2GPI antibodies could be a useful prognostic marker for the risk of thrombosis in SLE/APS patients.

Highlights

Antiphospholipid antibodies are associated strongly with thrombosis; the precise mechanism(s) by which they alter hemostasis to induce a hypercoagulable state remain unclear, numerous theories have been advanced [1]
It was observed that lupus anticoagulant (LA) could inhibit endothelial cell-mediated prothrombinase activity and the immunoglobulin G (IgG) fraction containing LA activity bound to phospholipid–PT complex [4]
The mean levels of aCL antibodies and other aPL-cofactor antibodies were significantly higher in patients with thrombosis (PAPS and systemic lupus erythematosus (SLE)/antiphospholipid syndrome (APS)) compared with SLE patients without APS, patients with deep vein thrombosis (DVT), or healthy controls

Summary

Introduction

Antiphospholipid antibodies (aPL) are associated strongly with thrombosis; the precise mechanism(s) by which they alter hemostasis to induce a hypercoagulable state remain unclear, numerous theories have been advanced [1]. The discovery that aPL antibodies recognize plasma proteins that bind to phospholipids rather than recognizing phospholipids themselves has been a major advancement in research into the antiphospholipid syndrome (APS). It is established that β2-glycoprotein I (β2GPI) is the most important antigen for aPL antibodies. PT was identified as an antigen for autoantibodies with LA activity as well as β2GPI. It could be accepted that antibodies to PT and β2GPI are two major autoantibodies responsible for LA activity, antiPT antibodies responsible for PT-dependent LA and anti-β2GPI antibodies for β2GPI-dependent LA [5]

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