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 lowdensity 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 enzymelinked immunosorbent assay (ELISA) using MDA-Lp(a) as antigen. Plasma levels of Lp(a) were determined. Anti-MDA-LDL, anticardiolipin antibodies (aCL), and anti- 2 -glycoprotein I antibodies (anti- 2 GPI) were also measured by ELISA. Inhibition assays were performed to determine the presence of crossreactivity 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%) ( 2 ؍ 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 ( 2 ؍ 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- 2 GPI 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- 2 GPI.
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.
* Except where indicated, patient n ϭ 104. APS ϭ antiphospholipid syndrome; SLE ϭ systemic lupus erythematosus; aCL ϭ anticardiolipin antibodies. † Some patients had Ͼ1 manifestation.