Oxidized low-density lipoprotein autoantibodies, chronic infections, and carotid atherosclerosis in a population-based study.
OBJECTIVE
We investigated whether associations exist between immune reactions to oxidized low-density lipoproteins (OxLDLs), chronic infections, and carotid atherosclerosis as quantified by ultrasound.


BACKGROUND
Atherosclerosis is a chronic immuno-inflammatory disease wherein both oxidized lipids and infectious agents are incriminated as possible contributors.


METHODS
We measured immunoglobulin (Ig)G and IgM autoantibody titers to copper-oxidized-LDL and malondialdehyde-LDL (OxLDL-AB), IgG and IgM apolipoprotein B-100-immune complexes (ApoB-IC), and titers of antibodies to Escherichia coli and chlamydial lipopolysaccharide (LPS), mycobacterial heat shock protein 65 (mHSP65), Chlamydia pneumoniae, Helicobacter pylori, and cytomegalovirus and evaluated their relationship to cardiovascular risk factors, chronic infections, and incident/progressive carotid atherosclerosis in the Bruneck study.


RESULTS
The OxLDL-AB and ApoB-IC levels remained stable over time as indicated by strong correlations between 1995 and 2000 measurements (p < 0.001 each). Significant associations existed between all OxLDL markers and antibody titers to pathogens, especially to E. coli-LPS and mHSP65. Both OxLDL-AB and ApoB-IC levels showed a rise with increasing pathogen burden. Notably, OxLDL-ABs were also elevated in subjects with chronic infection as defined by clinical criteria. Titers of IgG, but not IgM, OxLDL-AB, or ApoB-IC inversely correlated with total cholesterol, LDL cholesterol, and apoB concentrations. The IgG OxLDL markers were positively and IgM markers were inversely associated with incident and progressive carotid atherosclerosis in univariate analyses but were not independent predictors in multivariate analyses.


CONCLUSIONS
Our study provides evidence for an association between human oxLDL markers and chronic infections. Moreover, in this population-based study, neither IgG nor IgM OxLDL autoantibodies were independently predictive of atherosclerosis progression in the carotid arteries.
Mayr
Manuel
M
Department of Cardiac and Vascular Sciences, St. George's, University of London, London, United Kingdom.
Kiechl
Stefan
S
Tsimikas
Sotirios
S
Miller
Elizabeth
E
Sheldon
Joanna
J
Willeit
Johann
J
Witztum
Joseph L
JL
Xu
Qingbo
Q
D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000378:metabolism*; D002340:Carotid Artery Diseases / Q000150:complications / Q000276:immunology* / Q000378:metabolism*; D002908:Chronic Disease; D005260:Female; D006801:Humans; D007239:Infections / Q000150:complications / Q000276:immunology* / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction
D001323:Autoantibodies; D008077:Lipoproteins, LDL