Autoantibodies against malondialdehyde‐modified lipoprotein(a) in antiphospholipid syndrome

Objective To demonstrate the existence of antibodies that react against malondialdehyde (MDA)–modified lipoprotein(a) (MDA‐Lp[a]), a molecule that exhibits behavioral similarities to MDA‐modified low‐density lipoprotein (MDA‐LDL), and to assess the possible relationship of these antibodies (anti–MDA‐Lp[a]) to anti–MDA‐LDL antibodies (anti–MDA‐LDL) in the antiphospholipid syndrome (APS). Methods We studied 104 patients with APS (61 with primary APS and 43 with APS secondary to systemic lupus erythematosus) and 106 healthy controls. Anti–MDA‐Lp(a) were measured by enzyme‐linked immunosorbent assay (ELISA) using MDA‐Lp(a) as antigen. Plasma levels of Lp(a) were determined. Anti–MDA‐LDL, anticardiolipin antibodies (aCL), and anti–β2‐glycoprotein I antibodies (anti‐β2GPI) were also measured by ELISA. Inhibition assays were performed to determine the presence of cross‐reactivity between anti–MDA‐Lp(a) and anti–MDA‐LDL. Results Anti–MDA‐Lp(a) were detected in 38 of 104 patients (37%) but in only 6 of 106 controls (6%) (χ2= 28, P < 0.0001). Levels of anti–MDA‐Lp(a) were also higher in patients than in controls (P < 0.0001). Titers of these antibodies did not correlate with plasma levels of Lp(a). The presence of anti–MDA‐Lp(a) was significantly associated with that of anti–MDA‐LDL (χ2= 22.09, P < 0.0001). There was a strong correlation between the titers of anti–MDA‐Lp(a) and anti–MDA‐LDL (r = 0.59, P < 0.0001), and inhibition assays showed significant cross‐reactivity between the 2 populations of antibodies. Anticardiolipin antibodies and anti‐β2GPI were present in sera from 67 patients (64%) and 48 patients (46%), respectively. No correlation was found between the titer of anti–MDA‐Lp(a) and titers of either aCL or anti‐β2GPI. Conclusion We report for the first time the existence of autoantibodies against MDA‐Lp(a). The presence of antibodies reacting not only against MDA‐LDL but also against MDA‐Lp(a) supports the hypothesis of a role for oxidative phenomena in the pathogenesis of APS and atherosclerosis.