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

Objective. To demonstrate the existence of antibodies that react against ma londialdehyde (MDA)modified lipoprotein(a) (MDA-Lp[a]), a molecule that exh ibits 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 s yndrome (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. An ti-MDA-Lp(a) were measured by enzyme-linked immunosorbent assay (ELISA) usi ng MDA-Lp(a) as antigen, Plasma levels of Lp(a) were determined, Anti-MDA-L DL, anticardiolipin antibodies (aCL), and anti-beta(2)-glycoprotein I antib odies (anti-beta(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 on ly 6 of 106 controls (6%) (chi(2) = 28, P < 0.0001), Levels of anti-MDA-Lp( a) were also higher in patients than in controls (P < 0.0001). Titers of th ese 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 (c hi(2) = 22.09, P < 0.0001). There was a strong correlation between the tite rs of anti-MDA-Lp(a) and anti-MDA-LDL (r = 0.59, P < 0.0001), and inhibitio n assays showed significant cross-reactivity between the 2 populations of a ntibodies, Anticardiolipin antibodies and anti-beta(2)GPI were present in s era from 67 patients (64%) and 48 patients (46%), respectively, No correlat ion was found between the titer of anti-MDA-Lp(a) and titers of either aCL or anti-beta(2)GPI, Conclusion, We report for the first time the existence of autoantibodies ag ainst MDA-Lp(a), The presence of antibodies reacting not only against MDA-L DL but also against MDA-Lp(a) supports the hypothesis of a role for oxidati ve phenomena in the pathogenesis of APS and atherosclerosis.