Cross-reacting antibacterial auto-antibodies are produced within coronary atherosclerotic plaques of acute coronary syndrome patients

Filippo Canducci, Diego Saita, Chiara Foglieni, Maria Rosaria Piscopiello, Roberto Chiesa, Antonio Colombo, Domenico Cianflone, Attilio Maseri, Massimo Clementi, Roberto Burioni

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article numbere42283
JournalPLoS One
Volume7
Issue number8
DOIs
Publication statusPublished - Aug 6 2012

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autoantibodies
Atherosclerotic Plaques
Acute Coronary Syndrome
Monoclonal Antibodies
Antibodies
Bacterial Outer Membrane Proteins
Libraries
monoclonal antibodies
outer membrane proteins
Immunoglobulin Fragments
Bacteriophages
Lymphocytes
Confocal microscopy
lesions (animal)
immune response
Atherectomy
Membrane Proteins
Proteins
Blood
Proteus mirabilis

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Cross-reacting antibacterial auto-antibodies are produced within coronary atherosclerotic plaques of acute coronary syndrome patients. / Canducci, Filippo; Saita, Diego; Foglieni, Chiara; Piscopiello, Maria Rosaria; Chiesa, Roberto; Colombo, Antonio; Cianflone, Domenico; Maseri, Attilio; Clementi, Massimo; Burioni, Roberto.

In: PLoS One, Vol. 7, No. 8, e42283, 06.08.2012.

Research output: Contribution to journalArticle

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