title: Antibodies against native and oxidized cardiolipin and phosphatidylserine and phosphorylcholine in atherosclerosis development.
abstract: BACKGROUND
  Antibodies against cardiolipin and phosphatidylserine (anti-CL and anti-PS) are associated with thrombosis. In contrast, we determined that IgM antibodies against oxidized CL and PS (OxCL and OxPS) and phosphorylcholine (anti-PC) could be protection markers for cardiovascular disease (CVD).
  
  
  METHODS
  226 individuals with established hypertension (diastolic pressure>95 mmHg) from the European Lacidipine Study on Atherosclerosis. Antibodies were tested by ELISA. As a surrogate measure of atherosclerosis, the mean of the maximum intima-media thicknesses (IMT) in the far walls of common carotids and bifurcations was determined by ultrasonography at the time of inclusion and 4 years following inclusion.
  
  
  RESULTS
  Increases in IMT measures at follow-up were significantly less common in subjects which at baseline had high IgM anti-OxPS and anti-PC at above 75th percentile: OR 0,45, CI (0,23-0,86) and OR 0.37, CI (0,19-0,71), p = 0.0137 respectively and above 90th percentile: OR 0.32, CI (0,12-0,84) and OR 0.39, CI (0,15-1.00), p = 0.050 and OR 0,22, CI (0,08-0,59) p = 0,0029. IgM anti-OxCL was negatively associated with IMT increases (OR, 0.32, CI (0,12-0,84), p = 0231). There were no associations for IgM anti-PS or anti-CL. Anti-PC, as determined herein by a commercial ELISA, was strongly associated with data from our previously published in house ELISA (R = 0,87; p<0,0001).) Anti-PC was also a risk marker at low levels (below 25th percentile; OR = 2,37 (1,16-4,82), p = 0,0177).
  
  
  CONCLUSIONS
  High levels of IgM anti-OxPS and anti-OxCL, but not traditional anti-phospholipid antibodies (anti-PS and anti-CL), are associated with protection against atherosclerosis development. In addition, low IgM anti-PC was a risk marker but high a protection marker.
authors.affiliation: Institute of Environmental Medicine, Unit of Immunology and Chronic Disease, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Anna G
authors.initials: AG
authors.lastname: Frostegård
authors.affiliation: Institute of Environmental Medicine, Unit of Immunology and Chronic Disease, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Jun
authors.initials: J
authors.lastname: Su
authors.affiliation: Institute of Environmental Medicine, Unit of Immunology and Chronic Disease, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Xiang
authors.initials: X
authors.lastname: Hua
authors.affiliation: Institute of Environmental Medicine, Unit of Cardiovascular Epidemiology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Max
authors.initials: M
authors.lastname: Vikström
authors.affiliation: Institute of Environmental Medicine, Unit of Cardiovascular Epidemiology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Ulf
authors.initials: U
authors.lastname: de Faire
authors.affiliation: Institute of Environmental Medicine, Unit of Immunology and Chronic Disease, Karolinska Institutet, Stockholm, Sweden; Department of Acute Internal Medicine, Huddinge, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Frostegård
mesh_terms: D000328:Adult; D000906:Antibodies / Q000276:immunology* / Q000627:therapeutic use; D017209:Apoptosis / Q000276:immunology; D050197:Atherosclerosis / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy; D002308:Cardiolipins / Q000276:immunology* / Q000378:metabolism; D059168:Carotid Intima-Media Thickness; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D006973:Hypertension / Q000276:immunology / Q000473:pathology / Q000628:therapy; D007075:Immunoglobulin M / Q000276:immunology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D010718:Phosphatidylserines / Q000276:immunology*; D010767:Phosphorylcholine / Q000276:immunology*
chemical_list: D000906:Antibodies; D002308:Cardiolipins; D007075:Immunoglobulin M; D010718:Phosphatidylserines; D010767:Phosphorylcholine