Host immune response in H. pylori-infected patients of different ethnicities in Hospital Canselor Tuanku Muhriz (HCTM) UKM, Kuala Lumpur

Abstract

There is a marked difference in the pattern of gastritis due to infection of H. pylori among different ethnic groups in the same region or in the different regions in Malaysia and other parts of the world. The presence or absence of cagA gene only does not explain the diversity of disease outcomes induced by H. pylori infection. This study was carried out to characterize the cagA gene in Malaysian clinical isolates of H. pylori among different ethnic groups and to investigate the interaction between various interleukin expressions in gastric epithelial cells, in order to see whether differences in the host immune responses are somehow responsible for the different clinical outcomes caused by H. pylori infection. To test the hypothesis that cagA+ strains elicit a greater pro-inflammatory cytokine response in the gastric mucosa than cagA- strains, gastric biopsies were obtained from 230 dyspeptic patients. Of 230 patients, 140 (60.9%) were infected with H. pylori which gave positive results for at least one of the methods examined. H. pylori were detected in 15.7%, 27.9%, 20.7% and 60% of patients by culture, iRUT, histology and PCR, respectively. PCR identified H. pylori infection in 100% of biopsies with positive histology and culture. All biopsies with positive iRUT yielded positive PCR except two cases. The analysis shows there is differences in the prevalence of H. pylori infection among different ethnic groups. The Indians had the highest infection rate (76%), followed by the Chinese (60.4%) and the Malays (57.6%). Different types of cagA gene were identified. cagA type A-B-D strains were predominantly in Chinese (40%) compared to Indian (31.6%) and Malay (17.3%) whereas, infection with cagA type A-B-C strains were predominantly in Malay (78.8%) and in Indian (68.4%) compared to Chinese (54.5%). There was an association between H. pylori infection and endoscopic diagnosis of gastroduodenal diseases, as well as histopathological characteristics of gastric biopsies such as severe chronic gastritis, hyperplasia, intestinal metaplasia and atrophy. Of 25 H. pylori-infected patients with peptic ulceration, 23 (92%) were infected with cagA+ strains and had higher grades of inflammation in the gastric mucosa. Antral inflammation score was significantly associated with IL-8 production. Antral biopsies from infected patients, compared with uninfected patients, more often demonstrated IL-1β, IL-10 and IL-8 expression, and those infected with cagA+ compared with cagA- strains more often expressed IL 1β and showed elevated antral IL-8 and IL-10 levels. Patients with ulcer disease more often expressed higher antral IL-8 but lower expression of antral IL-1β and IL-10 than those without ulceration. In conclusion, these findings suggest that the ability to induce cytokines differs among the strains; cagA+ strains induce various kinds of cytokines and may cause severe inflammation, whereas cagA- strains induce IL-8 and IL-1β only weakly and may cause only mild inflammation. Most patients infected with the cagA+ strains have gastritis, these strains may not be equivalent to ulcerogenic strains which could be caused by other virulence factors such as cagPAI and VacA. However, infection with cagA+ H. pylori strains in association with higher grades of gastric inflammation, correlating with enhanced mucosal levels of IL-8 increased the risk of peptic ulceration.