title: Interaction of antibodies against cytomegalovirus with heat-shock protein 60 in pathogenesis of atherosclerosis.
abstract: BACKGROUND
  Infections and autoimmunity have been implicated in the pathogenesis of atherosclerosis. Cytomegalovirus has been shown to contribute to the disease. Autoantibodies against human heat-shock protein (HSP) 60 are present in most atherosclerotic patients, and their titre correlates with disease severity, suggesting that anti-HSP60 might be implicated in disease pathogenesis. We postulated that cytomegalovirus infection might induce antibodies able to bind human HSP60 and to cause endothelial-cell damage.
  
  
  METHODS
  We studied 180 patients with coronary-artery disease, raised high sensitivity C-reactive protein concentrations, and presence or absence of traditional risk factors; 90 patients with coronary-artery disease, normal values for high sensitivity C-reactive protein, and no traditional risk factors; and 98 controls. Individual sera were used to define the relevant epitope of HSP60 by ELISA. Affinity purified IgGs were used to identify endothelial cell-surface ligands by western blot and to induce apoptotic cell death.
  
  
  RESULTS
  We identified an 11 aminoacid sequence of HSP60 that was recognised by most patients with coronary-artery disease. This peptide shares homology with cytomegalovirus-derived proteins UL122 and US28. The same patients' sera recognised UL122-derived and US28-derived peptides. Purified IgGs against HSP60 and the viral peptides bound non-stressed human endothelial cells and induced endothelial-cell apoptosis by interaction with cell-surface molecules.
  
  
  CONCLUSIONS
  During cytomegalovirus infection, antibodies against the virus can arise that are able to crossreact with human HSP60 and cause apoptosis of non-stressed endothelial cells, which is judged a primary event in the pathogenesis of atherosclerosis.
authors.affiliation: Department of Experimental Medicine, University of Genova, Genova, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Bason
authors.forename: Roberto
authors.initials: R
authors.lastname: Corrocher
authors.forename: Claudio
authors.initials: C
authors.lastname: Lunardi
authors.forename: Patrizia
authors.initials: P
authors.lastname: Puccetti
authors.forename: Oliviero
authors.initials: O
authors.lastname: Olivieri
authors.forename: Domenico
authors.initials: D
authors.lastname: Girelli
authors.forename: Riccardo
authors.initials: R
authors.lastname: Navone
authors.forename: Ruggero
authors.initials: R
authors.lastname: Beri
authors.forename: Enrico
authors.initials: E
authors.lastname: Millo
authors.forename: Alberto
authors.initials: A
authors.lastname: Margonato
authors.forename: Nicola
authors.initials: N
authors.lastname: Martinelli
authors.forename: Antonio
authors.initials: A
authors.lastname: Puccetti
mesh_terms: D000914:Antibodies, Viral / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology; D017209:Apoptosis / Q000276:immunology; D018834:Chaperonin 60 / Q000276:immunology* / Q000378:metabolism; D003324:Coronary Artery Disease / Q000276:immunology* / Q000378:metabolism; D003429:Cross Reactions / Q000276:immunology; D003587:Cytomegalovirus / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000378:metabolism; D042783:Endothelial Cells / Q000276:immunology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020539:Sequence Analysis, Protein; D017385:Sequence Homology
chemical_list: D000914:Antibodies, Viral; D018834:Chaperonin 60