AFFINITY-PURIFIED CARDIOLIPIN-BINDING ANTIBODIES SHOW HETEROGENEITY IN THEIR BINDING TO OXIDIZED LOW-DENSITY-LIPOPROTEIN

Antiphospholipid antibodies in autoimmune sera have been shown to reac t with a complex of phospholipids (cardiolipin) and a plasma phospholi pid-binding protein, beta(2)-glycoprotein I (apolipoprotein H). The bi nding of these antibodies was inhibited by oxidized low-density lipopr otein (LDL) in sera from patients with systemic lupus erythematosus (S LE), suggesting cross-reactivity between antiphospholipid antibodies a nd antibodies binding to oxidized LDL. We purified antiphospholipid an tibodies by cardiolipin-polyacrylamide column from seven SLE sera and studied the reactivity of eluted fractions with cardiolipin-beta(2)-gl ycoprotein I complex and oxidized LDL (malondialdehyde-conjugated LDL) in solid-phase enzyme immunoassay. In four sera the binding of IgG an tibodies to cardiolipin-beta(2)-glycoprotein I complex and to oxidized LDL appeared in the same fractions, whereas in three sera reactivitie s against cardiolipin and oxidized LDL were observed, at least in part , in separate fractions. The binding to solid-phase cardiolipin was de pendent on the presence of exogenous beta(2)-glycoprotein I in all fra ctions. Our findings show that antiphospholipid antibodies are heterog eneous in their binding to oxidized LDL, indicating that these two ant ibodies may have different subspecificities. Some eluted fractions rea cted only with oxidized LDL, and did not show binding to cardiolipin-b eta(2)-glycoprotein I complex, suggesting that the lipid Dart in the a ntigenic complex might be responsible for the cross-reactivity of thes e antibodies. Accordingly, the biological functions of antibodies agai nst phospholipid-beta(2)-glycoprotein I complex and antibodies against oxidized LDL may also be different.