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

Canducci F, Saita D, Foglieni C, Piscopiello MR, Chiesa R, Colombo A, Cianflone D, Maseri A, Clementi M, Burioni R - PLoS ONE (2012)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Microbiology and Virology, Ospedale San Raffaele, Milan, Italy. Canducci.filippo@hsr.it

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.

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Study flow-chart.TAGLN  =  transgelin; OMPs  =  outer membrane proteins.
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pone-0042283-g001: Study flow-chart.TAGLN  =  transgelin; OMPs  =  outer membrane proteins.

Mentions: We now demonstrate, by molecular cloning in a phage display library of the IgG1/k repertoire present in coronary plaques and subsequent generation of human monoclonal antibodies, that B cells in the plaques of four different ACS patients produce antibody clones cross-reacting with the OMPs of gram- bacteria (K. pneumoniae and P mirabilis) and with transgelin (TAGLN), a cytoskeleton protein present in adult human smooth muscle cells (SMC) and other cell types (Figure 1) [23]. We also demonstrate that these antibodies recognized TAGLN expressed in cells with the phenotypic features of fibrocytes, a monocyte-derived-cell population present in coronary and carotid plaque sections. These cells are plastic monocyte-derived cells that migrate and differentiate under chronic inflammatory stimuli as previously observed in several autoimmune conditions such as scleroderma, autoimmune thyroiditis and rheumatoid arthritis [24]. The identification of local and exogenous antigenic stimuli recognized by the local adaptive immune response in human lesions explains the reason for the active recruitment of B cells in human lesions and has the potential of opening new vistas in the understanding of their role in the pathogenesis of acute coronary disease and to plan novel strategy in order to modulate the inflammatory component of the atherosclerotic process.


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

Canducci F, Saita D, Foglieni C, Piscopiello MR, Chiesa R, Colombo A, Cianflone D, Maseri A, Clementi M, Burioni R - PLoS ONE (2012)

Study flow-chart.TAGLN  =  transgelin; OMPs  =  outer membrane proteins.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3412836&req=5

pone-0042283-g001: Study flow-chart.TAGLN  =  transgelin; OMPs  =  outer membrane proteins.
Mentions: We now demonstrate, by molecular cloning in a phage display library of the IgG1/k repertoire present in coronary plaques and subsequent generation of human monoclonal antibodies, that B cells in the plaques of four different ACS patients produce antibody clones cross-reacting with the OMPs of gram- bacteria (K. pneumoniae and P mirabilis) and with transgelin (TAGLN), a cytoskeleton protein present in adult human smooth muscle cells (SMC) and other cell types (Figure 1) [23]. We also demonstrate that these antibodies recognized TAGLN expressed in cells with the phenotypic features of fibrocytes, a monocyte-derived-cell population present in coronary and carotid plaque sections. These cells are plastic monocyte-derived cells that migrate and differentiate under chronic inflammatory stimuli as previously observed in several autoimmune conditions such as scleroderma, autoimmune thyroiditis and rheumatoid arthritis [24]. The identification of local and exogenous antigenic stimuli recognized by the local adaptive immune response in human lesions explains the reason for the active recruitment of B cells in human lesions and has the potential of opening new vistas in the understanding of their role in the pathogenesis of acute coronary disease and to plan novel strategy in order to modulate the inflammatory component of the atherosclerotic process.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Microbiology and Virology, Ospedale San Raffaele, Milan, Italy. Canducci.filippo@hsr.it

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.

Show MeSH
Related in: MedlinePlus