Disease-Specific” Virulence Factors

Since the discovery of the H.pylori toxins VacA and CagA, which were linked to certain types of damage to the gastric mucosa, there have been continuous attempts to correlate them and other virulence factors with a specific manifestation or complication of H.pylori gastritis. Although some of these factors can affect the intensity of inflammation and, perhaps through this mechanism, may ultimately influence the outcome of gastritis, the virulence of H.pylori seems to be largely host dependent, and none of these factors are disease specific. Thus, at present, there is no clinical application for tests that purport to determine the potential pathogenicity of an individual patient’s H.pylori strain. The best studied putative virulence factor is the cytotoxin-associated gene product (Cag) A, the product of one of the genes in the cag pathogenicity island. Subjects infected with H.pylori with a functional cag pathogenicity island have elevated mucosal levels of interleukin-8, marked neutrophilic infiltration into the gastric mucosa, and an increased risk of developing a symptomatic outcome such as peptic ulcer or gastric cancer. However, the relationship between the presence of the cag pathogenicity island and outcome is not consistent in different geographic regions, especially in East Asia, where more than 90% of isolates possess the cag pathogenicity island. In Western countries, where H.pylori strains lacking the cag pathogenicity island are found in a higher percentage than in Asian countries, the increased likelihood of a symptomatic outcome can be seen. However, the presence of a functional cag pathogenicity island has no value in predicting current or future clinical presentation in individual patients.

Other putative pathogenicity factors include the following: IceA (induced by contact with epithelium), a bacterial restriction enzyme for which no biologic or epidemiologic evidence as a virulence factor in H.pylori–related disease has been confirmed; and VacA (vacuolatingcytotoxin), which has been subtyped into an s1 genotype (presumably associated with duodenal ulcer disease) and an s2 genotype with reportedly low ulcerogenic potential. A compilation of studies involving approximately 1500 isolates from Europe, the United States, and Asia has shown overwhelming that VacA genotyping is not useful to predict degree of inflammation, symptoms, presentation, or response to therapy.

The blood group antigen binding adhesin (BabA) is an outer membrane protein that appears to be involved in the adherence of H.pylori to Lewis-b (Le b) blood group antigens on gastric epithelial cells. A small study suggested that infection with strains with the babA2 gene, cagA +, and vacA s1 (triple-positive strains) may be correlated with duodenal ulcer, but a larger multinational study did not confirm the association.

Diagnosis

The diagnosis of H.pylori gastritis rests on the identification of H.pylori in the gastric mucosa. When the search for H.pylori relied exclusively on the availability of gastric biopsy specimens (for histopathology, rapid urease tests, or culture), only patients who required an endoscopic examination were tested. The development of increasingly accurate noninvasive tests allows the accurate diagnosis of H.pylori gastritis based on indirect methods, that is, without necessarily visually identifying or culturing the organism. Furthermore, the availability and popularization of new, simple, and inexpensive tests have expanded the indications to a greater variety of patients and settings, including self-referring patients in the general practitioners’ office.

Significant progress has been made also in our knowledge of factors that may influence the interpretation of the results and may interfere with the accuracy of each test. The prevalence of a condition in the population studied influences both the positive and negative predictive value of tests, even if a test’s sensitivity and specificity are independent values inherent to the test itself. Therefore, clinicians should be familiar not only with the performance parameters of the tests they use, but also with their potential interpretative pitfalls as well as with the prevalence of H.pylori in their patient population.

Дата добавления: 2015-11-14