title: Low levels of IgM antibodies to oxidized cardiolipin increase and high levels decrease risk of cardiovascular disease among 60-year olds: a prospective study.
abstract: BACKGROUND
  Antibodies against cardiolipin (aCL) are associated with increased risk of cardiovascular disease (CVD). We here determine the role of antibodies against oxidized CL (aOxCL).
  
  
  METHODS
  One third of sixty-year olds from the Stockholm County were screened (2039 men, 2193 women), where 211 incident CVD-cases and 633 age- and sex-matched controls were identified (5-7 year follow-up). Antibodies were determined by ELISA and uptake of oxLDL in macrophages by FACScan.
  
  
  RESULTS
  IgM aOxCL was lower among CVD cases than controls (p=0.024). aOxCL-levels were divided in quartiles with the highest quartile set as the reference group. After adjustment for smoking, BMI, type II diabetes, hypercholesterolaemia and hypertension, an increased risk was determined in the lowest quartile of IgM aOxCL (OR: 1.80, CI: 1.12-2.91, p=0.0159); OR for men in the lowest quartile was 2.46 (CI 1.34-4.53, p=0.0037) for CVD and for stroke: 12.28 (CI: 1.48-101.77, p=0.02). IgG aOxCL levels did not differ between quartiles in CVD-risk. High levels of IgM aOxCL (reaching significance above 86th) and IgG aOxCL (above 95th percentile) were associated with decreased risk of CVD (OR: 0.485, CI: 0.283-0.829; p=0.0082 and OR: 0.23, CI: 0.07-0.69; p=0.0091). aCL were not associated with CVD. oxCL but not CL competed out uptake of OxLDL in macrophages, and aOxLDL recognized oxCL but not CL. In contrast to aCL, aOxCL was not dependent on co-factor Beta2-glycoprotein-I.
  
  
  CONCLUSIONS
  aOxCL is a novel risk/protection marker for CVD, with therapeutic implications. OxCL competes with oxLDL for uptake in macrophages and the possibility that aOxCL inhibits such uptake by interfering with same or similar epitopes in oxCL and oxLDL should be further studied.
authors.affiliation: Institute of Environmental Medicine, Unit of Immunology and Chronic Disease, Karolinska Institutet, 17177 Stockholm, Sweden.
authors.forename: Jun
authors.initials: J
authors.lastname: Su
authors.forename: Xiang
authors.initials: X
authors.lastname: Hua
authors.forename: Max
authors.initials: M
authors.lastname: Vikström
authors.forename: Karin
authors.initials: K
authors.lastname: Leander
authors.forename: Bruna
authors.initials: B
authors.lastname: Gigante
authors.forename: Mai-Lis
authors.initials: ML
authors.lastname: Hellenius
authors.forename: Ulf
authors.initials: U
authors.lastname: de Faire
authors.forename: Johan
authors.initials: J
authors.lastname: Frostegård
mesh_terms: D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002308:Cardiolipins / Q000276:immunology* / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology / Q000276:immunology*; D016022:Case-Control Studies; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood*; D015994:Incidence; D008077:Lipoproteins, LDL / Q000378:metabolism; D016015:Logistic Models; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010084:Oxidation-Reduction; D011379:Prognosis; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology; D013997:Time Factors
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D002308:Cardiolipins; D007075:Immunoglobulin M; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein