Helicobacter pylori infection, ABO and secretor blood groups

Pathology

See Also

• ABH Antigens
• Adhesins?
• [Cell Adhesion Molecules (CAMs)]?
• Genetic polymorphism of interleukin-8 (IL-8) is associated with Helicobacter pylori-induced duodenal ulcer
• [Growth Factors]?
• H-h blood group system
• [Lewis antigens]?
• Non-secretors?
• Sialyl Lewis X (SLeX)
• Secretors

In the early 1950's it was first discovered that Type O appeared to predominate over the other types in the occurrence of all types of stomach ulcers at a rate of approximately two to one (1). These findings have been reproduced many times--over 25 studies in the last 20 years alone--with the same consistent result.

In several studies, non-secretors of ABO substances have been found to have a significantly higher rate of gastric and duodenal ulcers. Because of the increased prevalence of ulcers among non-secretors, it should come as no surprise that researchers have suggested that secretor status might influence bacterial colonization density or the ability of H. pylori to attach to gastroduodenal cells.

Because [non-secretor? non-secretors] are limited in their ability to secrete blood type antigens into the mucus secretions of their digestive tract, it has been proposed that they be at a competitive disadvantage from preventing H. pylori attachment.

Helicobacter pylori infection

Non-secretors, as a general rule, also show a significantly higher proportion of the H. pylori-seronegative subjects and a lower IgG (H. pylori immunoglobulin G (IgG?) antibody) immune response to H. pylori antigens as compared with the individuals of the secretor phenotype.

This might indicate that non-secretors are unable to mount an aggressive immune response against this organism in comparison with their secretor brethren. Evidence does suggest that both bacterial colonization and the ensuing inflammatory response are influenced, at least in part, by the ability to secrete blood group antigens. This relationship is strongest among Blood Type O non-secretors.

The genetics of the ABH secretor system interact to alter an individual's risk for ulcers. In several studies, non-secretors of ABH substances have been found to have a significantly higher rate of duodenal and peptic ulcers.

In fact the Copenhagen study found that the lifetime prevalence of peptic ulcer in men who were ABH non-secretors was 15% (statistically 15% of ABH non-secretors will have an ulcer at some point in their lives). And, the attributable risk of peptic ulcer in men who were Lewis (a + b-) or ABH non-secretors, with blood group O or A phenotypes was 37%. (2)

Overall, the relative risk of gastroduodenal disease for non-secretors compared with secretors is 1.9 (95% confidence interval). Duodenal ulcer patients are more likely to be non-secretors, and being a non-secretor acts as a multiplicative risk factor with the gene for hyperpepsinogenemia I to impact the risk of duodenal ulcer. (3)

Because of the increased prevalence of ulcers among non-secretors researchers have suggested that secretor status might influence bacterial colonization density or the ability of H. pylori to attach to gastroduodenal cells. With regards to the overall interaction with H. pylori infection, non-secretor status is generally considered to be a separate independent risk factor for gastroduodenal disease in addition to H. pylori infection.(4)

Because non-secretors are limited in their ability to secrete the [Lewis antigens? Lewis(b) blood group antigen] into the mucus of their digestive tract, it has been proposed that they be at a competitive disadvantage from preventing H. pylori attachment. In fact, the Lewis(b) antigens have been found to act as somewhat of a preferential target for H. pylori attachment. Thus, lack of Lewis(b) in mucosal fluids of ABH non secretors might indirectly contribute to colonization by H. pylori.

In a simplified sense, when the Lewis(b) antigen is free floating in the mucus, it probably acts to bind up some of the H. pylori before it can contact and attach to host tissue. In essence, being an ABH secretor probably provides an ability to put some biological decoys or metabolic chaff out into the gastric secretions that is very specific for H. pylori. Also, in ABH non-secretors the immune response against H. pylori appears to be lower and H. pylori appears to attach with higher aggressiveness and cause more inflammation. (5,6,7))

Individuals with Lewis (a+b-) ABH non-secretor phenotype also show a significantly higher proportion of the H. pylori-seronegative subjects and a lower IgG (H. pylori immunoglobulin G (IgG) antibody) immune response to H. pylori antigens as compared with the individuals of Lewis (a-b+)/secretor phenotype.

Evidence also indicates that 100% of non-secretors with duodenal ulcers culture positive for H. pylori infection. (8) However, among non-secretors with gastric ulcer, H. pylori is found in only about 12.5% of the cases. This is not observed among secretors, who are nearly equally likely to have H. pylori infection in either gastric or duodenal ulcer. (9)

Presence of the H.pylori adherence factor blood group Ag-binding adhesin (BabA; binding to Lewis(b) (Le(b))) is associated with ulcer disease, adenocarcinoma, and precancerous lesions. The importance of BabA for bacterial colonization and the inflammatory response is unknown. Infection with strains harboring BabA thereby augment a nonspecific immune response, whereas the Th1 response toward H. pylori appears to be independent of BabA, cytotoxin-associated gene A, or vacuolating cytotoxin.(10) Colbeck et. al. have hypothesized that diverse profiles of babA and babB reflect selective pressures for adhesion, which may differ across different hosts and within an individual over time. (11)

Helicobacter pylori infection is associated with an inflammatory response in the gastric mucosa, ultimately leading to cellular hyperproliferation and malignant transformation. Two main gene expression profiles were identified based on cluster analysis. The data obtained suggest a strong involvement of selected Toll-like receptors, [Cell Adhesion Molecules (CAMs)? adhesion molecules], chemokines?, and [Growth Factors? Interleukins] in the mucosal response. This pattern is clearly different from that observed using gastric epithelial cell lines infected in vitro with H. pylori. The presence of a "Helicobacter-infection signature," i.e., a set of genes that are up-regulated in biopsies from H. pylori-infected patients, could be derived from this analysis. The genotype of the bacteria (presence of genes encoding cytotoxin-associated Ag, vacuolating cytotoxin, and blood group Ag-binding adhesin) was analyzed by PCR and shown to be associated with differential expression of a subset of genes, but not the general gene expression pattern. The expression data of the array hybridization was confirmed by quantitative real-time PCR assays. Future studies may help identify gene expression patterns predictive of complications of the infection. (12)

Helicobacter pylori spontaneously switches lipopolysaccharide (LPS) Lewis (Le) antigens on and off (phase-variable expression), but the biological significance of this is unclear. Here, we report that Le+ H. pylori variants are able to bind to the C-type lectin DC-SIGN and present on gastric dendritic cells (DCs), and demonstrate that this interaction blocks [T Helper Lymphocyte? T helper cell (Th1)] development. In contrast, Le- variants escape binding to DCs and induce a strong Th1 cell response. In addition, in gastric biopsies challenged ex vivo with Le+ variants that bind DC-SIGN, interleukin 6 production is decreased, indicative of increased immune suppression. This indicates a role for LPS phase variation and Le antigen expression by H. pylori in suppressing immune responses through DC-SIGN.(13)

References