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 (SLE). Oxidized low-density lipoprotein (oxLDL) is implicated in cardiovascular disease, especially atherosclerosis, and cross-reacts with antibodies to cardiolipin (aCL). beta 2-GPI is a plasma protein participating in the coagulating cascade, and is also cofactor for aCL, and some aCL have been shown 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 is involved in the antigenicity of oxLDL. Antibodies to endothelial cells (aEC) correlate with diseases activity in SLE and vasculitis, and we recently showed that aEC are enhanced in cardiovascular disease such as borderline hypertension and early atherosclerosis. aEC were determined using EC from adult V. Saphena Magna. Antibody levels were determined by ELISA. aEC of IgG type were enhanced in 184 patients with SLE compared with 85 healthy controls. 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 epitopes with beta 2-GPI and with oxLDL, especially LPC. Phospholipids in EC membranes may thus be antigenic epitopes. beta 2-GPI may bind to these phospholipids, and become an autoantigen. LPC is formed by oxidation of phospholipids and/or proinflammatory factors leading to activation of phospholipase A2, and the findings indicate the potential role of both lipid oxidation and phospholipase A2 in SLE.
Wu
R
R
Department of Medicine, Karolinska Hospital, Stockholm, Sweden.
Svenungsson
E
E
Gunnarsson
I
I
Haegerstrand-Gillis
C
C
Andersson
B
B
Lundberg
I
I
Elinder
L S
LS
Frostegård
J
J
D000328:Adult; D017153:Antibodies, Anticardiolipin / Q000097:blood; D017152:Antibodies, Antiphospholipid / Q000097:blood; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens; D001667:Binding, Competitive; D016022:Case-Control Studies; D003429:Cross Reactions; D004730:Endothelium, Vascular / Q000276:immunology*; D000939:Epitopes; D005260:Female; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D008077:Lipoproteins, LDL / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008244:Lysophosphatidylcholines / Q000276:immunology; D008297:Male; D008875:Middle Aged; D053482:beta 2-Glycoprotein I
D017153:Antibodies, Anticardiolipin; D017152:Antibodies, Antiphospholipid; D001323:Autoantibodies; D001324:Autoantigens; D000939:Epitopes; D006023:Glycoproteins; D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines; D053482:beta 2-Glycoprotein I; C099252:oxidized low density lipoprotein