Animal model of autoimmune-induced atherosclerosis : Clinical significance of autoantibody against apolipoprotein A-I

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Apolipoprotein A-I (apoA-I) is the major protein contituent of HDL, in which apoA-I plays an important role in extracellular lipid transport and metabolism. ApoA-I is an activator of lichithin-cholesterol acyltransferase, and several studies have indicated that apoA-I plays a role as a ligand capable of interacting with the cellular binding site for HDL.This study provides the first information about natural autoantibodies against apoA-I in normal individuals. We showed that the anti-apoA-I autoantibodies bound effectively to oxidized HDL and also to apoA-I complexed with oxidized lipids. The epitope for the anti-apoA-I autoantibody was localized to N-terminus end of apoA-I, suggesting that the lipid peroxidation of HDL may cause a conformational change of apoA-I, resulting in the exposure of the N-terminal autologous antigenic site for the autoantibodies against apoA-I.We also found that serum level of anti-apoA-I autoantibody was reversely correlated with the serum concentration of HDL, implying the autoantibody plays a role in clearance of oxidixed HDL.Immunoglobulin gene sequences of the autoantibodies were also determined.