Antibodies against lysophosphatidylcholine and oxidized LDL in patients with SLE.
Lysophosphatidylcholine (LPC) is present in oxidized low density lipoprotein (oxLDL), which is implicated in atherosclerosis. Antibodies to cardiolipin (aCL) and oxLDL (aoxLDL) have been shown to crossreact. LPC is formed by hydrolysis of phosphatidylcholine (PC) in LDL and cell membranes, induced by phospholipase A2 or by oxidation. We here demonstrate the presence of enhanced antibody levels to LPC in 184 patients with SLE as compared to 85 healthy, age-matched controls. The antibody reactivity to LPC was not specifically related to oxidation of the fatty acid moiety in LPC, since LPC containing only the saturated fatty acid palmitic acid showed equivalent antibody levels as LPC containing unsaturated fatty acids. aPC were significantly lower as compared to aLPC, indicating that hydrolysis of PC at the sn-2 position increases the antigenic potential of the molecule. Beta-glycoprotein 1 was a cofactor for aCL, but not for aoxLDL or aLPC, and the antigenicity of these compounds is therefore not directly related to beta2GP1. There was a close correlation between aoxLDL, aCL and aLPC and both LPC and oxLDL competitively inhibited aCL-binding to CL. LPC, oxLDL and CL thus display a common antigenic site, which could be formed by removal of a fatty acid at the sn-2 position, possibly due to the activity to phospholipase A2 and/or oxidation. This study indicates the potential role of LDL-oxidation and phospholipase A2 in SLE.
Wu
R
R
Department of Medicine, Karolinska Hospital, Stockholm, Sweden.
Svenungsson
E
E
Gunnarsson
I
I
Andersson
B
B
Lundberg
I
I
Schäfer Elinder
L
L
Frostegård
J
J
D000328:Adult; D017153:Antibodies, Anticardiolipin / Q000097:blood*; D000915:Antibody Affinity; D002318:Cardiovascular Diseases / Q000276:immunology; D008078:Cholesterol, LDL / Q000276:immunology; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; 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; D008078:Cholesterol, LDL; D006023:Glycoproteins; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines; D053482:beta 2-Glycoprotein I; C099252:oxidized low density lipoprotein