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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.
AuthorsAmir Ravandi, S Matthijs Boekholdt, Ziad Mallat, Philippa J Talmud, John J P Kastelein, Nicholas J Wareham, Elizabeth R Miller, Joelle Benessiano, Alain Tedgui, Joseph L Witztum, Kay-Tee Khaw, Sotirios Tsimikas
JournalJournal of lipid research (J Lipid Res) Vol. 52 Issue 10 Pg. 1829-36 (Oct 2011) ISSN: 1539-7262 [Electronic] United States
PMID21821825 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antigen-Antibody Complex
  • Autoantibodies
  • Biomarkers
  • Immunoglobulin G
  • Immunoglobulin M
  • Lipoproteins, LDL
  • oxidized low density lipoprotein
Topics
  • Aged
  • Antigen-Antibody Complex (blood, immunology, metabolism)
  • Autoantibodies (blood, immunology, metabolism)
  • Biomarkers (blood, metabolism)
  • Cardiovascular Diseases (epidemiology, metabolism)
  • Case-Control Studies
  • Female
  • Humans
  • Immunoglobulin G (blood, metabolism)
  • Immunoglobulin M (blood, metabolism)
  • Inflammation (epidemiology, metabolism)
  • Lipoproteins, LDL (blood, immunology, metabolism)
  • Male
  • Middle Aged
  • Oxidation-Reduction
  • Risk Factors

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