title: IgM phosphorylcholine antibodies inhibit cell death and constitute a strong protection marker for atherosclerosis development, particularly in combination with other auto-antibodies against modified LDL.
abstract: BACKGROUND
  We have reported that anti-phosphorylcholine (anti-PC) IgM is a protection marker for human cardiovascular disease (CVD) and atherosclerosis. We here investigate the anti-PC autoantibodies in a well-defined cohort with regard to idiotype, atherosclerosis progression and mechanisms for its protective action.
  
  
  METHODS
  Serum levels and binding specificities of different anti-PC isotypes were determined in 226 hypertensive individuals enrolled in European Lacidipine Study on Atherosclerosis using ELISA. The mean of the maximum Intima-Media Thicknesses (IMT) in the far walls of common carotids and bifurcations was assessed at the time of inclusion, and four years afterwards. Apoptosis in immune cells was induced with lysophosphatidylcholine (LPC) and quantified using the MTT-assay.
  
  
  RESULTS
  Anti-PC IgM, IgA and IgG1 (but not IgG2) was negatively associated with IMT-progression. Combining anti-PC IgM with data on antibodies against oxidized- and malondialdehyde-modified LDL further strengthened this association. At very high levels, anti-PC IgM exhibited a striking negative association with atherosclerosis progression (OR 0.05; CI 0.006-0.40). Analysis of serum samples taken four years apart in study participants affirmed the stability of anti-PC IgM titers over time. Examination of fine specificities revealed that the protective isotypes (IgM, IgA and IgG1) are of the Group I idiotype whereas the non-protective IgG2 subclass was Group II. Anti-PC IgM inhibited LPC-induced cell death of immune cells.
  
  
  CONCLUSIONS
  Group I anti-PC antibodies, particularly of the IgM class, are independent protection markers for atherosclerosis progression. One potential mechanism of action is inhibition of LPC-induced cell cytotoxicity.
authors.affiliation: Institute of Environmental Medicine, Unit of Immunology and Chronic Disease, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Roland
authors.initials: R
authors.lastname: Fiskesund
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: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Ivana
authors.initials: I
authors.lastname: Bulatovic
authors.affiliation: Institute of Environmental Medicine, Division of Cardiovascular Epidemiology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Max
authors.initials: M
authors.lastname: Vikström
authors.affiliation: Institute of Environmental Medicine, Division of Cardiovascular Epidemiology, Karolinska Institutet, Stockholm, Sweden ; Department of Cardiology, Karolinska University Hospital, Solna, 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.
authors.forename: Johan
authors.initials: J
authors.lastname: Frostegård
keywords: Antibodies; Apoptosis; Biomarkers; Carotid intima media thickness; Phosphorylcholine