POTENTIAL ROLE OF MOLECULAR MIMICRY BETWEEN HELICOBACTER-PYLORI LIPOPOLYSACCHARIDE AND HOST LEWIS BLOOD-GROUP ANTIGENS IN AUTOIMMUNITY

Helicobacter pylori is involved in gastritis, gastric and duodenal ulc ers, gastric adenocarcinoma, and mucosa-associated lymphoid tissue lym phoma. Earlier studies already suggested a role for autoimmune phenome na 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. Imm unization of mice and rabbits with H. pylori cells or purified LPS ind uced an anti-Lewis x or y or anti-a type I response, yielding antibodi es 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 y ielded anti-Lewis antibodies also. The beta chain of gastric H+,K+-ATP ase, the parietal cell proton pump involved in acid secretion, contain ed Lewis y epitopes; gastric mucin contained Lewis x and y antigenic d eterminants. Growth in mice of a hybridoma that secretes H. pylori-ind uced anti-Lewis y monoclonal antibodies resulted in histopathological evidence of gastritis, which indicates a direct pathogenic role for an ti-Lewis antibodies. In conclusion, our observations demonstrate that molecular mimicry between H. pylori LPS and the host, based on Lewis a ntigens, and provide understanding of an autoimmune mechanism for H. p ylori-associated type B gastritis.