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Helicobacter pylori, Lewis antigens, and inflammation
  2. A P MORAN
  1. Laboratory of Molecular Biochemistry
  2. Department of Microbiology
  3. National University of Ireland, Galway, Ireland
  4. anthony.moran{at}

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Editor,—In a recent issue ofGut, Zheng et alreported that peptic ulcer disease was associated with increased expression of Lewis (Le) antigens but notcagA, iceA, orvacA in Chinese patients infected withHelicobacter pylori(

). These data raise as many questions as they answer and add further controversy to an intriguing area of microbiology and gastroenterology.

Lex and/or Ley blood group determinants are commonly found on the lipopolysaccharide (LPS) of H pylori isolates. These determinants have been identified on approximately 80–90% of isolates from all patient series examined to date.1-3 In our own series, 74/84 (88%) isolates expressed either Lex or Ley, with 47/84 (56%) of isolates coexpressing both determinants.4 No difference was identified in the prevalence of Lex or Leyexpression on H pylori strains isolated from ulcer patients and those strains isolated from patients with chronic gastritis, nor was an association demonstrated between host and bacterial Lewis phenotype. Since the report of Zhenget al we have reviewed our raw data regarding the prevalence of strains expressing two or more Lewis antigens. We found that two or more Le determinants were present in 9/12 (75%) isolates from duodenal ulcer patients and in 4/10 (40%) isolates from gastric ulcer patients. This gives an overall prevalence of 59% (13/22 isolates) for isolates from patients with ulcer disease. Thirty four of 62 (55%) patients with histological evidence of chronic gastritis also had isolates expressing two or more Le antigens.

A significant difference between H pyloristrains isolated from Chinese patients and those from our population is the finding of 48/108 (44%) isolates expressing three or more Le antigens compared with 11/84 (13%) isolates from a homogenous Irish population. In our series, only one strain expressed all class 1 and class 2 Le antigens—that is, Lex, Ley, and their isomers Lea and Leb. This unusually high prevalence of three or more antigenic determinants raises the question of whether or not these differences were due to strain variation or relate to antibody specificity. Zheng et alalso suggest that blood group A determinants have not been identified on H pylori isolates. We have previously described this determinant on a H pyloristrain expressing both Lex and Ley.4 5 However, the role of fucosylated blood group determinants such as blood group A, B, or H type-1 onH pylori LPS is as yet undetermined. This contrasts with the well established role of blood group A inH mustelae mediated gastric autoimmunity in the ferret model of gastric autoimmunity.6

These observations on the role of expression of multiple Le determinants are interesting, given the nature of our study population where patients with ulcerative disease made up only 26% of the overall study population. These individuals were infected with strains with a relatively well conserved pattern of Le determinant expression. Both genotypic conservation and adaptation of H pylori to host populations is well recognised inH pylori infection. Clonality is a recently described property of this bacterium and merits discussion in relation to Le determinants. In recent studies, H pylori strains isolated from 12 human hosts and 16 experimentally infected rodents showed Le expression to be highly uniform in isolates from different rodents infected for up to 20 weeks' duration.7 Substantial differences in Le expression were found among isolates from human patients and these differences were unrelated to the presence of random amplified polymorphic DNA sequences or cagA status. It has been suggested therefore that variation in H pylori Le expression in genetically similar microorgansims in human subjects may provide a pool of bacterial phenotypes for the continuous selection of host adapted populations for persistence.7 Clonality such as that reported for Le determinants could result in the presence of antibodies against the predominant Le epitope in strains from an individual host in vivo. A previous study has suggested that in mimicking host gastric epithelium,H pylori isolates not only express Lex and Ley, but that their relative proportion of expression corresponds to the host Le blood group phenotype (secretor status).3 We and others have found no evidence to support this hypothesis.4 8

In Asian populations, where the prevalence ofcagA genotype is high amongH pylori isolates, no association betweencagA genotype and ulceration has been found.9 Recent data have demonstrated that the prevalence of cagA+ H pyloriisolates is 44% among a group of 1025 men from 18 British towns.10 The consequence of this prevalence to disease in the general population is uncertain. However, given the association between cagA and more aggressive pathology among Western populations,11 the relationship between various virulence factors such as cagA and putative modifying or colonisation factors such as Le determinants must be clarified. Other data from our group have provided preliminary evidence that cagA, vacA, or vacA expression does not correlate with the level of Le antigen expression.12 However, no large dataset is available from a homogenous Western population. The original series that suggested that cagA status was related to Le antigen expression had 94 isolates from 19 countries and therefore is subject to marked bias.2

Lastly, one issue that requires further clarification is the relationship between bacterial Le antigen expression and neutrophil or lymphocytic infiltrates in the host gastric mucosa. In other work, we have shown that inflammatory responses to H pylori infection may be influenced at least in part by host Lea expression.13 Moreover, we have demonstrated that blood group O non-secretors had a significantly higher grade of lymphocyte infiltration of the gastric mucosa compared with non-O non-secretors.6 We have also demonstrated that Lex expression was associated with increased acute inflammatory infiltrates in patients with either ulcer disease (duodenal and gastric) or chronic gastritis.4 Based on the high prevalence of both Lex and Ley expression in Chinese patients, the role of inflammation needs to be explored further.


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