Gut 2000;47:10-11 ( July )

Commentary

See article on page 18

H pylori and Lewis antigens

The first 150 words of the full text of this article appear below.

Lipopolysaccharide (LPS) of many Helicobacter pylori strains expresses Lewis antigens (Le^x, Le^y, Le^a, Le^b) which are similar to those expressed by gastric epithelial cells ("molecular mimicry").¹ In addition, H pylori LPS displays phase variation in these antigensthat is, the high frequency, reversible switching of phenotype²; for instance, a strain that expresses Le^x may yield variants that express Le^y. As yet, no definite role has been assigned to these Lewis antigens, nor to phase variation, in the pathogenesis of gastric disease.

In this issue of Gut (see page 18), Zheng and colleagues³ report that H pylori strains isolated from Asian peptic ulcer patients express two or more Lewis antigens more often than strains from non-ulcer dyspepsia patients (89.6 v 73.2%; p=0.035). What could be the link between H pylori Lewis antigen expression and the development of pathology in the host?

(1)	Lewis antigens induce pathogenic antibodies. On infection, H pylori LPS may induce anti-Lex/y antibodies that bind not only to bacteria but also to host gastric epithelium, followed by complement fixation and tissue destruction.1 Indeed, H pylori infection of mice induces autoreactive anti-Lex/y antibodies.1 However, although high titres of antibodies to H pylori LPS are found in the serum of infected patients,1 these antibodies are not autoreactive and not directed against Lex/y (see Yokota and colleagues4).
(2)	Lewis antigen mimicry provides persistence through immune evasion. Analogous to ABO blood group antigens, a host that expresses Lex would be able to form anti-Ley antibodies but not antibodies directed at Lex. Consequently, Lex positive bacteria infecting a Lex positive host would escape immune attack and be able to persist while an Ley positive strain would not be able to persist. Experimental infection in monkeys confirms this concept: a H pylori strain isolated from Ley positive monkeys expressed mainly Ley; the same strain expressed mainly Lex after colonisation of Lex positive animals.5 This indicates that expression of the H pylori Lewis phenotype depends on the host; adaptation can occur by means of phase variation2 followed by selection through anti-Lex/y antibodies. Two of three studies in humans, however, failed to demonstrate the existence of a correlation between the phenotypes of the host and pathogen.6 Moreover, it has been shown that strains expressing Lex, and strains expressing Ley, can be isolated from the same patient.7 Finally, a shift in H pylori Lex/y antigen expression would be driven by anti-Lex/y antibodies and there is no evidence that these are formed in infected patients.4
(3)	Lewis antigens are involved in adhesion and colonisation. Expression of Lex/y is crucial for in vivo colonisation of mice: mutants with inactivated 1,4-galactosyltransferase8 or 3-fucosyltransferase genes (S L Martin, submitted) expressed no Lex/y and colonised less well than their Lex/y positive parent strains.

How would Le^x/y . . . [Full text of this article]

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Relevant Article

Association of peptic ulcer with increased expression of Lewis antigens but not cagA, iceA, and vacA in Helicobacter pylori isolates in an Asian population

P Y Zheng, J Hua, K G Yeoh, and B Ho
Gut 2000 47: 18-22. [Abstract] [Full Text] [PDF]

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