Coagulation and Transfusion Medicine / OXIDIZED LDL AND AUTOIMMUNE ANTIBODIES IN ANTIPHOSPHOLIPID SYNDROME

The prevalence and clinical significance of plasma oxidized low-density lipoprotein (oxLDL) and antibodies against oxLDL (anti-oxLDL) were evaluated in patients with antiphospholipid syndrome (APS). OxLDL and IgG anti-oxLDL were determined by enzyme-linked immunosorbent assay in plasma samples from 80 patients with APS. Positive values (mean + 3 SD) for oxLDL and anti-oxLDL were found in 21 (26%) and 19 (24%) of 80 patients with APS, respectively. These values were significantly higher than those in healthy subjects. Levels of oxLDL and anti-oxLDL antibodies in subgroupings of patients with APS who had experienced thrombotic events were compared. There were significant differences among the groups for the levels of both oxLDL and anti-oxLDL antibodies. Pairwise comparisons between the groups yielded similar but not identical results. There was a significant, positive correlation between levels of plasma oxLDL and anti-oxLDL. These results suggest that elevated levels of plasma oxLDL and anti-oxLDL may be risk factors and potential markers for thrombosis, especially for arterial thrombotic events, in patients with APS. Antiphospholipid syndrome (APS) has been defined as the occurrence of thrombosis (arterial or venous), recurrent fetal loss, and/or thrombocytopenia, in the presence of antiphospholipid antibodies (APAs).1-3 In this autoimmune disorder, atherosclerosis and arterial thrombosis contribute to morbidity and mortality.4-6 A wide spectrum of mechanisms has been proposed to account for arterial thrombosis in patients with APS. Oxidation makes low-density lipoprotein (LDL) more atherogenic,7 as suggested by the presence of oxidized LDL (oxLDL) particles in the early phase of atherosclerotic plaque formation.8,9 Epidemiologic studies have established that an elevated plasma level of LDL represents one of the most important risk factors for the development of atherosclerosis.10 On the other hand, oxLDL is immunogenic, and the generation of antibodies against oxLDL (antioxLDL) has been taken as a biologic signature of in vivo LDL oxidation.11,12 Oxidation of LDL can occur in vivo, and oxLDL may enhance LDL uptake by macrophage scavenger receptors, promoting the transformation of macrophages into foam cells.8 Anti-oxLDL has been demonstrated in chronic periaortitis,13 progressive carotid atherosclerosis,14 and APS,15 as well as in atherosclerotic lesions of rabbits and humans.8,16 Such antibodies recognize epitopes expressed in atherosclerotic lesions of rabbits and humans but not in normal arteries.11,17,18 Anti-oxLDL belongs to the family of APAs.19 APAs are associated with both arterial and venous thrombosis, although the risk factors for these two conditions are not the same.20 The question of the direct involvement of plasma oxLDL and anti-oxLDL in the occurrence of thrombosis remains unanswered. We studied the association of oxLDL, anti-oxLDL, and a thrombotic history in patients with APS. Coagulation and Transfusion Medicine / ORIGINAL ARTICLE Am J Clin Pathol 2001;116:760-767 761 © American Society of Clinical Pathologists Materials and Methods Patient Characteristics A total of 80 patients with APS ❚Table 1❚ and 72 healthy control subjects were included in the study. All patients fulfilled the criteria for APS proposed by Harris.21 The study patients were 17 men and 63 women, mean ± SD age, 40.0 ± 14.7 years (range, 19-77 years), and included 61 patients with primary APS, and 19 with systemic lupus erythematosus (SLE). Nine patients with cerebral transient ischemic attack were diagnosed by history alone. All other cases were objectively verified thrombotic events. Fetal loss was defined as recurrent (2 or more) abortions or more than 1 unexpected intrauterine fetal death after the second trimester. Thrombocytopenia was defined as a platelet count less than 100 × 103/μL (100 × 109/L). Control subjects were healthy volunteers (19 men and 53 women; mean ± SD age, 43.2 ± 12.4 years) without autoimmune diseases, bleeding disorders, unusual thrombotic events, or fetal losses.