AUTOANTIBODIES AGAINST OXIDIZED LOW-DENSITY LIPOPROTEIN

IN ANTIPHOSPHOLIPID SYNDROME

G. R. V. HUGHES

Department, Hospital Regional Carlos Haya, MaÂlaga, Spain

SUMMARY

The prevalence and clinical signi®cance of anti-oxidized low-density lipoprotein antibodies (anti-ox-LDL) were evaluated

in patients with the antiphospholipid syndrome (APS). Anti-ox-LDL were measured in the sera of 107 patients with APS

(64 primary APS, 43 secondary to systemic lupus erythematosus) by enzyme-linked immunosorbent assay (ELISA) utilizing

represent another potential marker of APS, particularly of patients prone to arterial thrombosis.

erythematosus.

plex of lipids and apoliprotein B100, and represents

one of the major cholesterol-carrier lipoproteins in

plasma. Epidemiological studies have established that

an elevated plasma level of LDL represents one of

the most important risk factors for the development

LDL can undergo several chemical modi®cations,

such as acetylation and oxidation [2]. The latter pro-

cess is of great interest because oxidation of LDL

development of atherosclerosis, as suggested by the

presence of oxidized-LDL (ox-LDL) particles in the

early phase of atherosclerotic plaque formation [6, 7].

Structural changes of LDL may enhance LDL uptake

by macrophage scavenger receptors, promoting the

transformation of macrophages into foam cells [8],

and may favour the recruitment and migration of

monocytes and leucocytes within arterial vessels [9].

On the other hand, oxidatively modi®ed LDL is

more immunogenic than its native counterpart, elicit-

ing speci®c anti-ox-LDL antibodies (anti-ox-LDL)

[2]. The latter have been detected in human sera from

a variety of in¯ammatory conditions. Initially

reported in patients with chronic periaortitis [10],

they were subsequently detected in subjects with caro-

tid atherosclerosis where they represented a marker

of progressive disease [11], and they were also found

in 80% of patients with systemic lupus erythematosus

(SLE) with and without anticardiolipin antibodies

(aCL) [12]. The same study suggested cross-reactivity

between aCL and anti-ox-LDL. Since aCL is one of

the antiphospholipid antibodies associated with the

antiphospholipid syndrome (APS), a thrombophilic

disorder characterized by arterial and venous throm-

bosis, recurrent fetal losses and thrombocytopenia

[13], we investigated the prevalence and clinical signi-

®cance of anti-ox-LDL in APS.

PATIENTS AND METHODS

Patients

A total of 107 patients were included in the study

[94 female and 13 male; mean age 41 yr (range 22±

66)]. Of these, 64 patients had primary APS (60%)

and 43 had APS secondary to SLE (40%). Clinical

features of the patients are reported in Table I. All

patients ful®lled the proposed criteria for the APS

[14]. One hundred and four sex- and age-matched

healthy controls were also included.

LDL isolation

Human LDL was isolated from pooled plasma of

healthy fasting adults by density gradient ultracentri-

fugation with BrK (Beckman L8-70 ultracentrifuge,

rotor VTI 65) at 65 000 r.p.m. for 35 min, followed

by a second ultracentrifugation with BrK at 49 000

r.p.m. for 18 h. The LDL layer was then dialysed for

a single band on 1% agarose gel electrophoresis in

borate bu€er.

Modi®cation of LDL

Malondialdehyde (MDA) was freshly generated

from malonaldehyde bis dimethylacetal by acid

964

Submitted 31 December 1996; revised version accepted 10 March

1997.

Correspondence to: M. A. Khamashta, Lupus Research Unit,

The Rayne Institute, St Thomas' Hospital, London SE1 7EH.