What is the pathophysiology of pediatric Helicobacter pylori (Hp) infection?

Updated: Nov 16, 2018
  • Author: Mutaz I Sultan, MBChB, MD; Chief Editor: Carmen Cuffari, MD  more...
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H pylori organisms are spiral-shaped gram-negative bacteria that are highly motile because of multiple unipolar flagella. They are microaerophilic and potent producers of the enzyme urease. H pylori inhabits the mucus adjacent to the gastric mucosa.

Important adaptive features that enhance survival of the organism in an acidic environment include its shape and motility, its reduced oxygen requirement, its adhesion molecules that are trophic to certain gastric cells, and its urease production. Bacterial urease converts urea to ammonium and bicarbonate, neutralizing gastric acid and providing protection in the hostile, highly acidic gastric environment. Some of the lipopolysaccharide of the organism mimics the Lewis blood group antigens in structure. This molecular mimicry also helps in the continued existence of H pylori in the unfavorable gastric environment. [4]

H pylori produces suspected disease-inducing factors, including urease, vacuolating cytotoxin, catalase, and lipopolysaccharide (LPS). Urease, a potent antigen, induces increased immunoglobulin G and immunoglobulin A production. Expression of vacuolating cytotoxin, which induces inflammatory cytokines, may be associated with more pronounced inflammation and increased propensity to cause disease. Catalase helps H pylori survive in the host by preventing the formation of reactive oxygen metabolites from hydrogen peroxide. The LPS outer membrane of H pylori is a less potent inducer of the host complement cascade.

Cytotoxin-associated antigen (CagA) is probably the most important virulence factor in H pylori infection . An individual infected with CagA-negative strains is likely only to develop chronic gastritis and have only a small chance of developing peptic ulcer disease or gastric cancer. In contrast, infection with CagA-positive strains greatly increases the risk of peptic ulcer disease and gastric cancer. Translocating the CagA protein into the gastric epithelial cells causes rearrangement of the host cytoskeleton and alters cell signaling and perturbs cell cycle control. Furthermore, CagA-positive strains are known to induce the expression of a DNA-editing enzyme, which leads to accumulation of mutations in the tumor suppressor p53. [5]

CagA in situ expression is increased in children with H pylori infection who have peptic ulcers and may play a role in the pathogenesis of peptic ulcer disease (PUD). [6]

CagA can be divided in 2 types, the East-Asian type and the Western type, according to the repeat sequences of the 3′ region of cagA. Individuals infected with East-Asian type cagA strains are reported to have higher risk of PUD or gastric cancer than those with Western-type cagA strains. [7]

The association between serum anti-CagA antibodies and gastric cancer in East Asian countries (Japan, Korea, and China) was clarified in a meta-analysis of case-control studies with age and sex-matched controls, in which 10 studies with a total of 4325 patients were identified. [8] CagA seropositivity was associated with gastric cancer compared with gastritis, even in East Asian countries, although the odds ratio (OR) in East Asian countries was smaller than that of another meta-analysis, which included Western countries.

Duodenal ulcer–promoting gene (DupA) is the first genetic factor of H pylori detected to be associated with a differential susceptibility to duodenal ulcer and gastric cancer. Thus, it can be considered a disease-specific virulence marker. [7] The prevalence of dupA was significantly higher in strains from patients with duodenal ulcer but lower in those with gastric cancer (42% vs 9%, on average).

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