Oxidized Low-Density Lipoprotein Autoantibodies, Chronic Infections, and Carotid Atherosclerosis in a Population-Based Study Manuel Mayr, Stefan Kiechl, Sotirios Tsimikas, Elizabeth Miller, Joanna Sheldon, Johann Willeit, Joseph L. Witztum, Qingbo Xu Autoantibodies to oxidized low-density lipoprotein (OxLDL) and apolipoprotein B-100-immune complexes (ApoB-IC) were measured in the Bruneck study and correlated with antipathogen antibodies, chronic infections, and the presence and progression of carotid atherosclerosis. Significant associations were obtained for OxLDL markers with antibodies to Escherichia coliand chlamydial lipopolysaccharide, mycobacterial heat shock protein 65, Chlamydia pneumoniae, Helicobacter pylori, and cytomegalovirus (p < 0.001 for most associations) and with chronic infections as defined by clinical criteria. Titers of immunoglobulin G OxLDL antibodies inversely correlated with total cholesterol, LDL cholesterol, and ApoB concentrations. However, OxLDL autoantibodies and ApoB-IC did not emerge as independent risk predictors of carotid atherosclerosis in multivariate analyses. We investigated whether associations exist between immune reactions to oxidized low-density lipoproteins (OxLDLs), chronic infections, and carotid atherosclerosis as quantified by ultrasound. Atherosclerosis is a chronic immuno-inflammatory disease wherein both oxidized lipids and infectious agents are incriminated as possible contributors. 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 coliand 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. 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. 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.