Abstract 296: Autoantibody Profiling as Rapid and Non-Invasive Diagnostic Tool for the Presence of Ruptured Atherosclerotic Lesions
Background Novel biomarkers, such as circulating autoantibody signatures, may improve early detection and treatment of ruptured atherosclerotic lesions and accompanying cardiovascular disease.
Methods Using a phage-display library derived from cDNAs preferentially expressed in ruptured human atherosclerotic plaques, we performed serological antigen selection (SAS) to isolate displayed cDNA products specifically interacting with serum samples of patients (n=10) with ruptured atherosclerotic lesions. The identified peptides were subsequently evaluated on an independent validation set of sera from 38 patients with ruptured atherosclerotic lesions, 23 patients with stable atherosclerotic plaques and 10 healthy age and sex matched controls.
Results A set of 2 phage-displayed-peptides had 100 percent specificity and 74 percent sensitivity in discriminating patients with proven ruptured atherosclerotic lesions from patients with stable plaques and healthy controls. Detailed bio-informatics revealed a high level of homology (91% identity) with a human natural killer cell lectin-like receptor for peptide 1, while the second peptide encoded a thus far unknown protein generated from the 3′ UTR of human protein kinase C eta. Furthermore, in a relatively small cohort (6 sera per group) a set of 7 phage-displayed-peptides (including peptide 1 and 2) showed a 100% sensitivity and specificity in the identification of patients with proven ruptured plaques. Detailed bio-informatics of additional peptides and extension of the cohort tested is currently ongoing.
Conclusions Autoantibody profiling of ruptured plaque specific antigens constitutes a promising new biomarker approach for rapid and non-invasive diagnosis of ruptured atherosclerotic lesions in humans.