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

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.