Potential role of molecular mimicry between Helicobacter pylori lipopolysaccharide and host Lewis blood group antigens in autoimmunity

Ben J. Appelmelk, Ina Simoons-Smit, Riccardo Negrini, Anthony P. Moran, Gerald O. Aspinall, John G. Forte, Theodora De Vries, Hu Quan, Theo Verboom, Janneke J. Maaskant, Paolo Ghiara, Ernst J. Kuipers, Elisabeth Bloemena, Thea M. Tadema, Reid R. Townsend, Kamala Tyagarajan, Jim M. Crothers, Mario A. Monteiro, Antonella Savio, Johannes De Graaff

Research output: Contribution to journalArticlepeer-review

365 Scopus citations

Abstract

Helicobacter pylori is involved in gastritis, gastric and duodenal ulcers, gastric adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma. Earlier studies already suggested a role for autoimmune phenomena in H. pylori-linked disease. We now report that lipopolysaccharides (LPS) of H. pylori express Lewis y, Lewis x, and H type I blood group structures similar to those commonly occurring in gastric mucosa. Immunization of mice and rabbits with H. pylori cells or purified LPS induced an anti-Lewis x or y or anti-H type 1 response, yielding antibodies that bound human and murine gastric glandular tissue, granulocytes, adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma cells. Experimental oral infections in mice or natural infection in humans yielded anti-Lewis antibodies also. The β chain of gastric H+,K+-ATPase, the parietal cell proton pump involved in acid secretion, contained Lewis y epitopes; gastric mucin contained Lewis x and y antigenic determinants. Growth in mice of a hybridoma that secretes H. pylori-induced anti-Lewis y monoclonal antibodies resulted in histopathological evidence of gastritis, which indicates a direct pathogenic role for anti-Lewis antibodies. In conclusion, our observations demonstrate that molecular mimicry between H. pylori LPS and the host, based on Lewis antigens, and provide understanding of an autoimmune mechanism for H. pylori- associated type B gastritis.

Original languageEnglish
Pages (from-to)2031-2040
Number of pages10
JournalInfection and immunity
Volume64
Issue number6
DOIs
StatePublished - Jun 1996

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