Cross-reactivity of Anti-CagA antibodies with vascular wall antigens -: Possible pathogenic link between Helicobacter pylori infection and atherosclerosis

Background-Helicobacter pylori-CagA positive strains have been shown to be associated with atherosclerosis. However, the pathogenesis is still undetermined. The aim Of this Study was to determine whether anti-CagA antibodies cross-react with antigens of normal and atherosclerotic arteries. Methods and Results-Eight umbilical cord sections, 14 atherosclerotic artery sections, and 10 gastrointestinal tract sections were examined by immunohistochemistry using polyclonal anti-Cag-A antibodies. Five atherosclerotic and 3 normal artery samples were also lysed in ice-cold lysis buffer containing protease inhibitors and were immunoprecipitated using the same antibodies. Anti-CagA antibodies reacted with cytoplasm and nuclei of smooth muscle cells in umbilical cord and atherosclerotic vessel sections, cytoplasm of fibroblasts-like cells in intimal atherosclerotic plaques, and the cell membranes of endothelial cells. Anti-CagA antibodies also specifically immunoprecipitated 2 high molecular weight antigens of 160 and 180 kDa from both normal and atherosclerotic artery lysates. Conclusions-Anti-CagA antibodies cross-react with antigens of both normal and atherosclerotic blood vessels. We speculate that the binding of anti-CagA antibodies to those antigens in injured arteries could influence the progression of atherosclerosis in CagA-positive H pylori-infected patients.