title: Autoantibodies against malondialdehyde-modified lipoprotein(a) in antiphospholipid syndrome.
abstract: 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-beta2-glycoprotein I antibodies (anti-beta2GPI) 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%) (chi2 = 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 (chi2 = 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-beta2GPI 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-beta2GPI.
  
  
  CONCLUSIONS
  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.
authors.affiliation: The Rayne Institute, St. Thomas' Hospital, London, UK.
authors.forename: F I
authors.initials: FI
authors.lastname: Romero
authors.forename: T
authors.initials: T
authors.lastname: Atsumi
authors.forename: F J
authors.initials: FJ
authors.lastname: Tinahones
authors.forename: J M
authors.initials: JM
authors.lastname: Gómez-Zumaquero
authors.forename: O
authors.initials: O
authors.lastname: Amengual
authors.forename: M A
authors.initials: MA
authors.lastname: Khamashta
authors.forename: G R
authors.initials: GR
authors.lastname: Hughes
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000276:immunology; D016736:Antiphospholipid Syndrome / Q000097:blood / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D017270:Lipoprotein(a) / Q000187:drug effects / Q000276:immunology*; D008077:Lipoproteins, LDL / Q000276:immunology; D008297:Male; D008315:Malondialdehyde / Q000494:pharmacology*; D008875:Middle Aged; D053482:beta 2-Glycoprotein I
chemical_list: D000925:Anticoagulants; D001323:Autoantibodies; D006023:Glycoproteins; D017270:Lipoprotein(a); D008077:Lipoproteins, LDL; D053482:beta 2-Glycoprotein I; D008315:Malondialdehyde