title: Noninvasive diagnosis of ruptured peripheral atherosclerotic lesions and myocardial infarction by antibody profiling.
abstract: Novel biomarkers, such as circulating (auto)antibody signatures, may improve early detection and treatment of ruptured atherosclerotic lesions and accompanying cardiovascular events, such as myocardial infarction. Using a phage-display library derived from cDNAs preferentially expressed in ruptured peripheral human atherosclerotic plaques, we performed serological antigen selection to isolate displayed cDNA products specifically interacting with antibodies in sera from patients with proven ruptured peripheral atherosclerotic lesions. Two cDNA products were subsequently evaluated on a validation series of patients with peripheral atherosclerotic lesions, healthy controls, and patients with coronary artery disease at different stages. Our biomarker set was able to discriminate between patients with peripheral ruptured lesions and patients with peripheral stable plaques with 100% specificity and 76% sensitivity. Furthermore, 93% of patients with an acute myocardial infarction (AMI) tested positive for our biomarkers, whereas all patients with stable angina pectoris tested negative. Moreover, 90% of AMI patients who initially tested negative for troponin T, for which a positive result is known to indicate myocardial infarction, tested positive for our biomarkers upon hospital admission. In conclusion, antibody profiling constitutes a promising approach for noninvasive diagnosis of atherosclerotic lesions, because a positive serum response against a set of 2 cDNA products showed a strong association with the presence of ruptured peripheral atherosclerotic lesions and myocardial infarction.
authors.affiliation: Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, Maastricht, The Netherlands. kitty.cleutjens@path.unimaas.nl
authors.forename: Kitty B J M
authors.initials: KB
authors.lastname: Cleutjens
authors.forename: Birgit C G
authors.initials: BC
authors.lastname: Faber
authors.forename: Mat
authors.initials: M
authors.lastname: Rousch
authors.forename: Ruben
authors.initials: R
authors.lastname: van Doorn
authors.forename: Tilman M
authors.initials: TM
authors.lastname: Hackeng
authors.forename: Cornelis
authors.initials: C
authors.lastname: Vink
authors.forename: Piet
authors.initials: P
authors.lastname: Geusens
authors.forename: Hugo
authors.initials: H
authors.lastname: ten Cate
authors.forename: Johannes
authors.initials: J
authors.lastname: Waltenberger
authors.forename: Vadim
authors.initials: V
authors.lastname: Tchaikovski
authors.forename: Marc
authors.initials: M
authors.lastname: Lobbes
authors.forename: Veerle
authors.initials: V
authors.lastname: Somers
authors.forename: Anneke
authors.initials: A
authors.lastname: Sijbers
authors.forename: Darcey
authors.initials: D
authors.lastname: Black
authors.forename: Peter J E H M
authors.initials: PJ
authors.lastname: Kitslaar
authors.forename: Mat J A P
authors.initials: MJ
authors.lastname: Daemen
mesh_terms: D000368:Aged; D000787:Angina Pectoris / Q000097:blood / Q000473:pathology; D000941:Antigens / Q000276:immunology; D050197:Atherosclerosis / Q000097:blood / Q000175:diagnosis* / Q000473:pathology*; D001323:Autoantibodies / Q000097:blood; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000097:blood / Q000473:pathology; D003430:Cross-Sectional Studies; D018076:DNA, Complementary / Q000302:isolation & purification; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000175:diagnosis* / Q000473:pathology*; D019151:Peptide Library; D016491:Peripheral Vascular Diseases / Q000097:blood / Q000473:pathology; D015203:Reproducibility of Results; D012422:Rupture, Spontaneous / Q000473:pathology; D012680:Sensitivity and Specificity
chemical_list: D000941:Antigens; D001323:Autoantibodies; D015415:Biomarkers; D018076:DNA, Complementary; D019151:Peptide Library