title: Affinity-purified cardiolipin-binding antibodies show heterogeneity in their binding to oxidized low-density lipoprotein.
abstract: Antiphospholipid antibodies in autoimmune sera have been shown to react with a complex of phospholipids (cardiolipin) and a plasma phospholipid-binding protein, beta 2-glycoprotein I (apolipoprotein H). The binding of these antibodies was inhibited by oxidized low-density lipoprotein (LDL) in sera from patients with systemic lupus erythematosus (SLE), suggesting cross-reactivity between antiphospholipid antibodies and antibodies binding to oxidized LDL. We purified antiphospholipid antibodies by cardiolipin-polyacrylamide column from seven SLE sera and studied the reactivity of eluted fractions with cardiolipin-beta 2-glycoprotein I complex and oxidized LDL (malondialdehyde-conjugated LDL) in solid-phase enzyme immunoassay. In four sera the binding of IgG antibodies to cardiolipin-beta 2-glycoprotein I complex and to oxidized LDL appeared in the same fractions, whereas in three sera reactivities against cardiolipin and oxidized LDL were observed, at least in part, in separate fractions. The binding to solid-phase cardiolipin was dependent on the presence of exogenous beta 2-glycoprotein I in all fractions. Our findings show that antiphospholipid antibodies are heterogeneous in their binding to oxidized LDL, indicating that these two antibodies may have different subspecificities. Some eluted fractions reacted only with oxidized LDL, and did not show binding to cardiolipin-beta 2-glycoprotein I complex, suggesting that the lipid part in the antigenic complex might be responsible for the cross-reactivity of these antibodies. Accordingly, the biological functions of antibodies against phospholipid-beta 2-glycoprotein I complex and antibodies against oxidized LDL may also be different.
authors.affiliation: Department of Immunobiology, National Public Health Institute, Helsinki, Finland.
authors.forename: O
authors.initials: O
authors.lastname: Vaarala
authors.forename: M
authors.initials: M
authors.lastname: Puurunen
authors.forename: M
authors.initials: M
authors.lastname: Lukka
authors.forename: G
authors.initials: G
authors.lastname: Alfthan
authors.forename: M
authors.initials: M
authors.lastname: Leirisalo-Repo
authors.forename: K
authors.initials: K
authors.lastname: Aho
authors.forename: T
authors.initials: T
authors.lastname: Palosuo
mesh_terms: D000328:Adult; D000368:Aged; D017153:Antibodies, Anticardiolipin / Q000737:chemistry* / Q000302:isolation & purification*; D000915:Antibody Affinity; D001053:Apolipoproteins / Q000276:immunology; D003429:Cross Reactions; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D008077:Lipoproteins, LDL / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D008875:Middle Aged; D010084:Oxidation-Reduction; D053482:beta 2-Glycoprotein I
chemical_list: D017153:Antibodies, Anticardiolipin; D001053:Apolipoproteins; D006023:Glycoproteins; D008077:Lipoproteins, LDL; D053482:beta 2-Glycoprotein I