D-095. The Host Humoral Response against Helicobacter pylori Lipopolysaccharide is Influenced by cagA Status

E. L. Sanabria-Valentín, G. I. Perez-Perez, M. J. Blaser;
New York Univ. Sch. of Med., New York, NY.

Helicobacter pylori can persist in the gastric environment for the lifetime of its host despite a strong humoral response against it. H. pylori LPS has a substantially lower bioactivity level than members of Enterobacteriaceae, suggesting a role in persistence. The H. pylori O-antigen is composed of repeating units of human sugar epitopes, most notably fucosylated Lewis antigens, and is involved in molecular mimicry and adaptation to the host. We hypothesized that the humoral response against H. pylori LPS is influenced by host and bacterial factors, and that modifications in the LPS affect its recognition by antibodies in subjects colonized by these bacteria. We developed an assay to measure IgG levels against purified H. pylori LPS and used sera from 153 human subjects with diverse clinical diagnoses, who varied in H. pylori and cagA status. We found that 32.2% of H. pylori+ subjects (n=93) develop an IgG response to H. pylori-LPS versus 3.3% of apparently H. pylori- subjects (p<0.0001). Being an LPS responder was not correlated with subject age or severity of H. pylori-related disease. Using LPS derived from isogenic fucosylation-deficient H. pylori mutants, we determined that host LPS recognition is not affected by the LPS Lewis fucosylation pattern. Among the H. pylori+ subjects, those who had cagA+ strains were more likely to be an LPS-responder than those with cagA- strains (50% vs. 22% respectively; OR = 3.54(1.30-9.79); p=0.005). LPS derived from either wild type cagA- strains or from isogenic mutants lacking the cagPAI were not recognized by serum from subjects that recognized LPS from cagA+ strains. From these studies, we conclude that H. pylori+ hosts may be LPS responders or not, which does not relate to LPS Lewis status, but is most closely related with cagPAI status of the colonizing H. pylori strain. These data suggest that the H. pylori cagPAI contains genes involved in LPS-modification.