title: Cross-reacting antibacterial auto-antibodies are produced within coronary atherosclerotic plaques of acute coronary syndrome patients.
abstract: Coronary atherosclerosis, the main condition predisposing to acute myocardial infarction, has an inflammatory component caused by stimuli that are yet unknown. We molecularly investigated the nature of the immune response within human coronary lesion in four coronary plaques obtained by endoluminal atherectomy from four patients. We constructed phage-display libraries containing the IgG1/kappa antibody fragments produced by B-lymphocytes present in each plaque. By immunoaffinity, we selected from these libraries a monoclonal antibody, arbitrarily named Fab7816, able to react both with coronary and carotid atherosclerotic tissue samples. We also demonstrated by confocal microscopy that this monoclonal antibody recognized human transgelin type 1, a cytoskeleton protein involved in atherogenesis, and that it co-localized with fibrocyte-like cells transgelin+, CD68+, CD45+ in human sections of coronary and carotid plaques. In vitro fibrocytes obtained by differentiating CD14+ cells isolated from peripheral blood mononuclear cells also interacted with Fab7816, thus supporting the hypothesis of a specific recognition of fibrocytes into the atherosclerotic lesions. Interestingly, the same antibody, cross-reacted with the outer membrane proteins of Proteus mirabilis and Klebsiella pneumoniae (and possibly with homologous proteins of other enterobacteriaceae present in the microbiota). From all the other three libraries, we were able to clone, by immunoaffinity selection, human monoclonal antibodies cross-reacting with bacterial outer membrane proteins and with transgelin. These findings demonstrated that in human atherosclerotic plaques a local cross-reactive immune response takes place.
authors.affiliation: Laboratory of Microbiology and Virology, Ospedale San Raffaele, Milan, Italy. Canducci.filippo@hsr.it
authors.forename: Filippo
authors.initials: F
authors.lastname: Canducci
authors.forename: Diego
authors.initials: D
authors.lastname: Saita
authors.forename: Chiara
authors.initials: C
authors.lastname: Foglieni
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Piscopiello
authors.forename: Roberto
authors.initials: R
authors.lastname: Chiesa
authors.forename: Antonio
authors.initials: A
authors.lastname: Colombo
authors.forename: Domenico
authors.initials: D
authors.lastname: Cianflone
authors.forename: Attilio
authors.initials: A
authors.lastname: Maseri
authors.forename: Massimo
authors.initials: M
authors.lastname: Clementi
authors.forename: Roberto
authors.initials: R
authors.lastname: Burioni
mesh_terms: D054058:Acute Coronary Syndrome / Q000276:immunology* / Q000473:pathology; D000595:Amino Acid Sequence; D000907:Antibodies, Bacterial / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D001323:Autoantibodies / Q000096:biosynthesis* / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology; D015153:Blotting, Western; D002339:Carotid Arteries / Q000276:immunology / Q000473:pathology; D048430:Cell Shape; D020650:Combinatorial Chemistry Techniques; D003324:Coronary Artery Disease / Q000276:immunology* / Q000473:pathology; D003429:Cross Reactions / Q000276:immunology*; D005347:Fibroblasts / Q000473:pathology; D005455:Fluorescent Antibody Technique; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry / Q000276:immunology; D007074:Immunoglobulin G / Q000737:chemistry / Q000276:immunology; D007711:Klebsiella pneumoniae / Q000276:immunology; D008840:Microfilament Proteins / Q000276:immunology; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000276:immunology; D019151:Peptide Library; D010641:Phenotype; D058226:Plaque, Atherosclerotic / Q000276:immunology* / Q000473:pathology; D011513:Proteus mirabilis / Q000276:immunology; D014020:Tissue Extracts
chemical_list: D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D001323:Autoantibodies; D001425:Bacterial Outer Membrane Proteins; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D008840:Microfilament Proteins; D009124:Muscle Proteins; D019151:Peptide Library; D014020:Tissue Extracts; C051615:transgelin