title: Relationship of IgG and IgM autoantibodies and immune complexes to oxidized LDL with markers of oxidation and inflammation and cardiovascular events: results from the EPIC-Norfolk Study.
abstract: Levels of IgG and IgM autoantibodies (AA) to malondialdehyde (MDA)-LDL and apoB-immune complexes (ICs) were measured in 748 cases and 1,723 controls in the EPIC-Norfolk cohort and their association to coronary artery disease (CAD) events determined. We evaluated whether AA and IC modify CAD risk associated with secretory phospholipase A(2) (sPLA(2)) type IIA mass and activity, lipoprotein-associated PLA(2) activity, lipoprotein (a) [Lp(a)], oxidized phospholipids on apoB-100 (OxPL/apoB), myeloperoxidase, and high sensitivity C-reactive protein. IgG ICs were higher in cases versus controls (P = 0.02). Elevated levels of IgM AA and IC were inversely associated with Framingham Risk Score and number of metabolic syndrome criteria (p range 0.02-0.001). In regression analyses adjusted for age, smoking, diabetes, LDL-cholesterol, HDL-cholesterol, and systolic blood pressure, the highest tertiles of IgG and IgM AA and IC were not associated with higher risk of CAD events compared with the lowest tertiles. However, elevated levels of IgM IC reduced the risk of Lp(a) (P = 0.006) and elevated IgG MDA-LDL potentiated the risk of sPLA(2) mass (P = 0.018). This epidemiological cohort of initially healthy subjects shows that IgG and IgM AA and IC are not independent predictors of CAD events but may modify CAD risk associated with elevated levels of oxidative biomarkers.
authors.affiliation: Division of Cardiology, Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Amir
authors.initials: A
authors.lastname: Ravandi
authors.forename: S Matthijs
authors.initials: SM
authors.lastname: Boekholdt
authors.forename: Ziad
authors.initials: Z
authors.lastname: Mallat
authors.forename: Philippa J
authors.initials: PJ
authors.lastname: Talmud
authors.forename: John J P
authors.initials: JJ
authors.lastname: Kastelein
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Wareham
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Miller
authors.forename: Joelle
authors.initials: J
authors.lastname: Benessiano
authors.forename: Alain
authors.initials: A
authors.lastname: Tedgui
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Witztum
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
authors.forename: Sotirios
authors.initials: S
authors.lastname: Tsimikas
mesh_terms: D000368:Aged; D000936:Antigen-Antibody Complex / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000378:metabolism*; D007075:Immunoglobulin M / Q000097:blood / Q000378:metabolism*; D007249:Inflammation / Q000453:epidemiology / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D012307:Risk Factors
chemical_list: D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D015415:Biomarkers; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein