ORIGINAL COMMUNICATION Influence of CagA-positive Helicobacter pylori strains on atherosclerotic carotid disease Petra Bago Roz ˇankovic ´ • Arijana Lovrenc ˇic ´ Huzjan • Hrvoje C ˇ upic ´ • Ines Jajic ´ Benc ˇic ´ • Silvio Bas ˇic ´ • Vida Demarin Received: 26 July 2010 / Revised: 20 October 2010 / Accepted: 29 October 2010 Ó Springer-Verlag 2010 Abstract Citotoxin-associated gene-A (CagA)-positive Helicobacter pylori strains have been associated with occurrence and destabilization of coronary atherosclerotic plaques. However, data on the relationship between CagA- positive H. pylori infection and carotid artery instability are lacking. Thus, the role of CagA antigen in patients with symptomatic and asymptomatic carotid atherosclerotic plaques was investigated. A total of 64 patients with advanced carotid artery stenosis, including 33 patients with symptomatic and 31 patients with asymptomatic internal carotid artery stenosis, verified by duplex ultrasound, all undergoing carotid endarterectomy, were studied. The control group consisted of 65 subjects without a history or presence of vascular diseases. Serology for H. pylori and CagA antigen was assessed in all participants. Specimens of atherosclerotic plaques obtained from all patients dur- ing carotid endarterectomy were analyzed immunohisto- chemically using anti-CagA monoclonal antibodies. The ultrasonographic plaque characteristics were also esti- mated. CagA antibody titers were significantly higher in symptomatic patients (8.8; range, 5.8–32.7) compared to asymptomatic patients (4.7; range, 2.1–8.8; P = 0.005) and the control group (5.0; range 2.2–7.9; P \ 0.001). There was significant difference in echolucency (C25% soft material) between the symptomatic and asymptomatic groups (P = 0.034) by ultrasonographic evaluation. Posi- tive immunoreactivity between monoclonal CagA anti- bodies and antigens within atherosclerotic specimens was significantly higher among symptomatic patients compared to asymptomatic patients (97.0 vs. 74.2%; P = 0.009). H. pylori may play a role in the pathogenesis of the ath- erosclerotic process due to autoimmune mechanisms and even contribute to destabilization of carotid atherosclerotic plaques. Keywords Symptomatic carotid artery disease Á Helicobacter pylori Á CagA antigen Á Molecular mimicry Introduction Atherosclerosis is a chronic inflammatory disease of the arteries resulting in ischemic heart disease, cerebrovascular disorders, and gangrene of the extremities [1, 2]. The pathogenesis of atherosclerosis involves the processes of vascular injury, inflammation, and thrombosis; however, the stimulus that triggers the inflammatory response remains unclear. Persistent infectious pathogens, such as Chlamydia pneumoniae, Cytomegalovirus, Porphyromonas gingivalis, and Helicobacter pylori, might induce immune responses in their host and promote the development of atherosclerosis, including its thrombotic and thromboem- bolic complications [3–5]. P. B. Roz ˇankovic ´(&) Á S. Bas ˇic ´ Department of Neurology, Clinical Hospital Dubrava, Avenija Gojka S ˇ us ˇka 6, 10000 Zagreb, Croatia e-mail: petrabago@yahoo.com A. L. Huzjan Á V. Demarin Department of Neurology, University Hospital Sestre milosrdnice, Vinogradska cesta 29, 10000 Zagreb, Croatia H. C ˇ upic ´ Department of Pathology, University Hospital Sestre milosrdnice, Vinogradska cesta 29, 10000 Zagreb, Croatia I. J. Benc ˇic ´ Department of Microbiology, University Hospital Sestre milosrdnice, Vinogradska cesta 29, 10000 Zagreb, Croatia 123 J Neurol DOI 10.1007/s00415-010-5824-9