CagA antigen of helicobacter pylori and coronary instability: Insight from a clinico-pathological study and a meta-analysis of 4241 cases

Francesco Franceschi, Giampaolo Niccoli, Giuseppe Ferrante, Antonio Gasbarrini, Alfonso Baldi, Marcello Candelli, Florinda Feroce, Nathalie Saulnier, Micaela Conte, Davide Roccarina, Gaetano A. Lanza, Giovanni Gasbarrini, Silveri Nicolò Gentiloni, Filippo Crea

Research output: Contribution to journalArticle

Abstract

Background: Cytotoxin-associated gene-A (CagA) antigen is expressed by some virulent strains of Helicobacter pylori (H. pylori). The role of CagA antigen in coronary instability is unknown. We performed a clinico-pathological study and a meta-analysis in the attempt to shed new light on this complex issue. Methods: In the clinico-pathological study, 38 patients with unstable angina (UA), 25 patients with stable angina (SA), 21 patients with normal coronary arteries (NCA) and 50 age and sex matched healthy volunteers were enrolled. Serology for CagA was assessed in all patients. Specimens of atherosclerotic plaques were obtained from all patients by directional coronary atherectomy, and prepared for immunohistochemistry using anti-CagA monoclonal antibodies. The meta-analysis includes 9 studies assessing the association between seropositivity to CagA strains and acute coronary events. Results: The titre of anti-CagA antibodies was significantly higher in patients with unstable angina (161 ± 90 RU/ml) compared to those with stable angina (83 ± 59 RU/ml p <0.02), NCA (47.3 ± 29 RU/ml p <0.01) and healthy controls (73 ± 69 p <0.02). Anti-CagA antibodies recognized antigens localized inside coronary atherosclerotic plaques in all specimens from both stable and unstable patients. In the meta-analysis, seropositivity to CagA was significantly associated with the occurrence of acute coronary events with an odds ratio (OR) of 1.34 (95% CI, 1.15-1.58, p = 0.0003). Conclusions: Taken together these findings suggest that in a subset of patients with unstable angina, an intense immune response against CagA-positive H. pylori strains might be critical to precipitate coronary instability mediated by antigen mimicry between CagA antigen and a protein contained in coronary atherosclerotic plaques.

Original languageEnglish
Pages (from-to)535-542
Number of pages8
JournalAtherosclerosis
Volume202
Issue number2
DOIs
Publication statusPublished - Feb 2009

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Cytotoxins
Helicobacter pylori
Meta-Analysis
Antigens
Genes
Unstable Angina
Atherosclerotic Plaques
Stable Angina
Coronary Vessels
Coronary Atherectomy
Molecular Mimicry
Antibodies
Serology
Healthy Volunteers
Immunohistochemistry
Odds Ratio
Monoclonal Antibodies

Keywords

  • Acute coronary syndromes
  • Helicobacter pylori
  • Infection
  • Meta-analysis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

CagA antigen of helicobacter pylori and coronary instability : Insight from a clinico-pathological study and a meta-analysis of 4241 cases. / Franceschi, Francesco; Niccoli, Giampaolo; Ferrante, Giuseppe; Gasbarrini, Antonio; Baldi, Alfonso; Candelli, Marcello; Feroce, Florinda; Saulnier, Nathalie; Conte, Micaela; Roccarina, Davide; Lanza, Gaetano A.; Gasbarrini, Giovanni; Gentiloni, Silveri Nicolò; Crea, Filippo.

In: Atherosclerosis, Vol. 202, No. 2, 02.2009, p. 535-542.

Research output: Contribution to journalArticle

Franceschi, F, Niccoli, G, Ferrante, G, Gasbarrini, A, Baldi, A, Candelli, M, Feroce, F, Saulnier, N, Conte, M, Roccarina, D, Lanza, GA, Gasbarrini, G, Gentiloni, SN & Crea, F 2009, 'CagA antigen of helicobacter pylori and coronary instability: Insight from a clinico-pathological study and a meta-analysis of 4241 cases', Atherosclerosis, vol. 202, no. 2, pp. 535-542. https://doi.org/10.1016/j.atherosclerosis.2008.04.051
Franceschi, Francesco ; Niccoli, Giampaolo ; Ferrante, Giuseppe ; Gasbarrini, Antonio ; Baldi, Alfonso ; Candelli, Marcello ; Feroce, Florinda ; Saulnier, Nathalie ; Conte, Micaela ; Roccarina, Davide ; Lanza, Gaetano A. ; Gasbarrini, Giovanni ; Gentiloni, Silveri Nicolò ; Crea, Filippo. / CagA antigen of helicobacter pylori and coronary instability : Insight from a clinico-pathological study and a meta-analysis of 4241 cases. In: Atherosclerosis. 2009 ; Vol. 202, No. 2. pp. 535-542.
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abstract = "Background: Cytotoxin-associated gene-A (CagA) antigen is expressed by some virulent strains of Helicobacter pylori (H. pylori). The role of CagA antigen in coronary instability is unknown. We performed a clinico-pathological study and a meta-analysis in the attempt to shed new light on this complex issue. Methods: In the clinico-pathological study, 38 patients with unstable angina (UA), 25 patients with stable angina (SA), 21 patients with normal coronary arteries (NCA) and 50 age and sex matched healthy volunteers were enrolled. Serology for CagA was assessed in all patients. Specimens of atherosclerotic plaques were obtained from all patients by directional coronary atherectomy, and prepared for immunohistochemistry using anti-CagA monoclonal antibodies. The meta-analysis includes 9 studies assessing the association between seropositivity to CagA strains and acute coronary events. Results: The titre of anti-CagA antibodies was significantly higher in patients with unstable angina (161 ± 90 RU/ml) compared to those with stable angina (83 ± 59 RU/ml p <0.02), NCA (47.3 ± 29 RU/ml p <0.01) and healthy controls (73 ± 69 p <0.02). Anti-CagA antibodies recognized antigens localized inside coronary atherosclerotic plaques in all specimens from both stable and unstable patients. In the meta-analysis, seropositivity to CagA was significantly associated with the occurrence of acute coronary events with an odds ratio (OR) of 1.34 (95{\%} CI, 1.15-1.58, p = 0.0003). Conclusions: Taken together these findings suggest that in a subset of patients with unstable angina, an intense immune response against CagA-positive H. pylori strains might be critical to precipitate coronary instability mediated by antigen mimicry between CagA antigen and a protein contained in coronary atherosclerotic plaques.",
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T2 - Insight from a clinico-pathological study and a meta-analysis of 4241 cases

AU - Franceschi, Francesco

AU - Niccoli, Giampaolo

AU - Ferrante, Giuseppe

AU - Gasbarrini, Antonio

AU - Baldi, Alfonso

AU - Candelli, Marcello

AU - Feroce, Florinda

AU - Saulnier, Nathalie

AU - Conte, Micaela

AU - Roccarina, Davide

AU - Lanza, Gaetano A.

AU - Gasbarrini, Giovanni

AU - Gentiloni, Silveri Nicolò

AU - Crea, Filippo

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N2 - Background: Cytotoxin-associated gene-A (CagA) antigen is expressed by some virulent strains of Helicobacter pylori (H. pylori). The role of CagA antigen in coronary instability is unknown. We performed a clinico-pathological study and a meta-analysis in the attempt to shed new light on this complex issue. Methods: In the clinico-pathological study, 38 patients with unstable angina (UA), 25 patients with stable angina (SA), 21 patients with normal coronary arteries (NCA) and 50 age and sex matched healthy volunteers were enrolled. Serology for CagA was assessed in all patients. Specimens of atherosclerotic plaques were obtained from all patients by directional coronary atherectomy, and prepared for immunohistochemistry using anti-CagA monoclonal antibodies. The meta-analysis includes 9 studies assessing the association between seropositivity to CagA strains and acute coronary events. Results: The titre of anti-CagA antibodies was significantly higher in patients with unstable angina (161 ± 90 RU/ml) compared to those with stable angina (83 ± 59 RU/ml p <0.02), NCA (47.3 ± 29 RU/ml p <0.01) and healthy controls (73 ± 69 p <0.02). Anti-CagA antibodies recognized antigens localized inside coronary atherosclerotic plaques in all specimens from both stable and unstable patients. In the meta-analysis, seropositivity to CagA was significantly associated with the occurrence of acute coronary events with an odds ratio (OR) of 1.34 (95% CI, 1.15-1.58, p = 0.0003). Conclusions: Taken together these findings suggest that in a subset of patients with unstable angina, an intense immune response against CagA-positive H. pylori strains might be critical to precipitate coronary instability mediated by antigen mimicry between CagA antigen and a protein contained in coronary atherosclerotic plaques.

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