Low levels of IgM antibodies to phosphorylcholine predict cardiovascular disease in 60-year old men: effects on uptake of oxidized LDL in macrophages as a potential mechanism

J Autoimmun. 2010 Mar;34(2):73-9. doi: 10.1016/j.jaut.2009.05.003. Epub 2009 Sep 2.

Abstract

Objective: We here determine the role of IgM antibodies against phosphorylcholine (anti-PC) in prediction of cardiovascular disease (CVD) and on macrophage uptake of Oxidized LDL (OxLDL).

Methods: From a screening of 4232 subjects, 60-year-old (2039 men and 2193 women), 211 incident cases of CVD (myocardial infarction, ischemic stroke, or hospitalized angina pectoris) and 633 age- and sex-matched controls were identified through a 5-7 year follow-up. Serum levels of IgM anti-PC was determined by ELISA. Anti-PC was extracted from pooled human IgM and the effect of anti-PC on the uptake of OxLDL was studied by FACScan.

Results: Relative risks (RR) with 95% confidence intervals (CI) by quartiles of anti-PC levels with quartile 4 set as the reference value (RR = 1.0) and adjusted for smoking, BMI, type II diabetes, hypercholesterolaemia, and high blood pressure yielded an excess risk for CVD only for those within the lowest quartile of anti-PC values with an RR of 1.37 (CI 0.87-2.16). However, for men stronger associations were noted with increasing multivariately adjusted RRs from quartile 4 to quartile 1. Subjects within quartile 1 (values below 29.7 U/ml) had a significantly increased RR of 1.96 (CI 1.09-3.55). Further adjustments for hsCRP gave essentially the same results. No excess risk was noted for women. Specific anti-PC could be extracted from IgM and these antibodies inhibited macrophage uptake of OxLDL.

Conclusions: Low IgM anti-PC could be a novel risk marker for CVD among men. One possible mechanism could be inhibition of uptake of oxLDL in macrophages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Biomarkers / blood
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / diagnosis*
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / immunology*
  • Cell Line
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoglobulin M / blood
  • Immunoglobulin M / pharmacology*
  • Lipoproteins, LDL / metabolism
  • Macrophages / drug effects
  • Macrophages / immunology
  • Macrophages / metabolism*
  • Macrophages / pathology
  • Male
  • Middle Aged
  • Phagocytosis / drug effects
  • Phagocytosis / immunology
  • Phosphorylcholine / immunology*
  • Prognosis
  • Risk
  • Sex Factors
  • Sweden

Substances

  • Biomarkers
  • Immunoglobulin M
  • Lipoproteins, LDL
  • oxidized low density lipoprotein
  • Phosphorylcholine