Antibodies to adult human endothelial cells cross-react with oxidized low-density lipoprotein and beta(2)- glycoprotein I (beta(2)-GPI) in systemic lupus erythematosus

Cardiovascular manifestations are common in systemic lupus erythematosus (S LE). Oxidized low-density lipoprotein (oxLDL) is implicated in cardiovascul ar disease, especially atherosclerosis, and cross-reacts with antibodies to cardiolipin (aCL). beta(2)-GPI is a plasma protein participating in the co agulating cascade, and is also cofactor for aCL, and some aCL have been sho wn to be directed against beta(2)-GPI and/or complexes between beta(2)-GPI and phospholipids. Lysophosphatidylcholine (LPC) is a phospholipid present both in oxLDL and in damaged endothelium, and we recently showed that LPC i s involved in the antigenicity of oxLDL. Antibodies to endothelial cells (a EC) correlate with disease activity in SLE and vasculitis, and we recently showed that aEC are enhanced in cardiovascular diseases such as borderline hypertension and early atherosclerosis. aEC were determined using EC from a dult V. Saphena Magna. Antibody levels were determined by ELISA. aEC of IgG type were enhanced in 184 patients with SLE compared with 85 healthy contr ols. There was a close correlation between aoxLDL, aCL, aLPC, a beta(2)-GPI and aEC. Binding of sera to EC was competitively inhibited by beta(2)-GPI, LPC and oxLDL. Taken together, the data indicate that EC share antigenic e pitopes with beta(2)-GPI and with oxLDL, especially LPC. Phospholipids in E C membranes may thus be antigenic epitopes. beta(2)-GPI may bind to these p hospholipids, and become an autoantigen. LPC is formed by oxidation of phos pholipids and/or proinflammatory factors leading to activation of phospholi pase A(2), and the findings indicate the potential role of both lipid oxida tion and phospholipase A(2) in SLE.