Persisting chronic gastritis and elevated Helicobacter pylori antibodies after successful eradication therapy

AIM: The persistence of chronic inflammation in gastric mucosa and elevated Helicobacter pylori antibodies after successful eradication therapy are common findings in clinical practice. We studied their possible association with each other and disappearance in long-term follow up, as well as their possible connection with gastric atrophy. PATIENTS AND METHODS: The study population consisted of 108 dyspeptic patients with successful eradication therapy median 6.4 years earlier. The patients underwent gastroscopy, and biopsies from antrum and corpus were evaluated by an experienced pathologist. Serum samples collected from 77 patients were studied for H. pylori antibodies, parietal cell antibodies, as well as for pepsinogen I, pepsinogen II, and gastrin-17 levels. RESULTS: The prevalence of chronic gastric inflammation and elevated H. pylori antibodies after successful eradication therapy decreased by time, but still after 5 years, 17 of 51 (33%) subjects had elevated H. pylori antibodies and 14 of 68 (21%) had a mild inactive chronic inflammation in gastric mucosa. In patients with and without chronic inflammation in gastric mucosa, elevated H. pylori antibodies were detected in three of 10 (30%) and 14 of 41 (34%), elevated parietal cell antibodies in one of 10 (10%) and six of 41 (15%), low pepsinogen I in one of 10 (10%) and none of 41, and elevated gastrin-17 in three of 10 (30%) and six of 41 (15%), respectively. CONCLUSION: More than 5 years after successful H. pylori eradication therapy, mild persistent chronic inflammation may occur in gastric mucosa in up to one-fifth and elevated H. pylori antibodies even in one-third of patients, although these two are independent phenomena.     

Mucosal production of antigastric autoantibodies in Helicobacter pylori gastritis

Background. Apart form bacterial virulence factors of Helicobacter pylori , certain host factors influence the pathogenesis of H. pylori gastritis. In particular, antigastric autoantibodies that are detectable in the sera of a substantial proportion of H. pylori were shown to correlate with the development of gastric atrophy. The aim of this study was to analyze the possible antigastric autoimmune response in H. pylori gastritis at the site where the action is, i.e., in the gastric mucosa.
Material and Methods. Gastric biopsy specimens from antrum and corpus mucosa of 24 H. pylori –infected and of 33 noninfected patients were cultured for 3 days, and tissue culture supernatants were analyzed for the amount of locally produced IgA and IgG. Antigastric autoantibodies were screened in the sera and in the supernatants by means of immunohistochemistry.
Results. The infected patients had significantly higher concentrations of locally produced IgA, whereas the IgG concentrations were virtually the same in infected and noninfected patients. IgG or IgA antigastric autoantibodies, or both, were detectable only in the sera (38%) and supernatants (17%) of infected patients. Interestingly, the patient with the strongest local autoimmune response showed body-predominant H. pylori gastritis, with destruction of gastric glands and atrophy of the body mucosa.
Conclusions. These results demonstrate that antigastric autoimmune reactions are detectable at the site of the disease and might be relevant for the pathogenesis of gastric mucosa atrophy in H. pylori gastritis.     

幽门螺杆菌对PCNA及HSP60在慢性胃炎中的表达的影响

目的研究HSP60与PCNA在幽门螺杆菌感染慢性胃炎组织中的表达及其意义。方法免疫细胞化学检测Hp 和Hp-慢性胃炎患者胃窦粘膜内的PCNA和HSP60。结果PCNA在浅表性胃炎以弱阳性或阳性表达为主,在萎缩性胃炎以阳性或强阳性表达为主。与Hp-患者相比,Hp 患者胃粘膜PCNA的表达显著增强,两者之间差异显著(P<0·05);HSP60在Hp 患者浅表性胃炎、萎缩性胃炎的阳性率分别为40·0%和76·9%,Hp 患者胃粘膜HSP60的表达比Hp-患者强(P<0·05)。结论幽门螺杆菌的感染增强了PCNA、HSP60在胃粘膜中的表达,与胃粘膜的病理特征有密切的关系,两者可能是胃粘膜病变趋势或临床病理特征的重要指标。     

The pathological examinations of gastric mucosa in patients with Helicobacter pylori-positive and -negative pernicious anemia

Background. The basic histopathological finding in gastric mucosa is chronic atrophic gastritis in patients with pernicious anemia.
Materials and Methods. We evaluated the frequency of Helicobacter pylori and pathological examinations of gastric mucosa in pernicious anemia (n = 30) by endoscopical findings and biopsy. The results were compared with gastric mucosa specimens of patients with H. pylori –positive nonulcer dyspepsia (n = 36) and H. pylori –negative nonulcer dyspepsia (n = 21).
Results. H. pylori was diagnosed in 12 patients (40%) with pernicious anemia. Fundal biopsy examinations showed atrophic gastritis in 30 patients (100%), intestinal metaplasia in 13 patients (43.3%), lymphoid follicle in 15 patients (50%), and dysplasia in 6 patients (20%). Antral biopsy examinations showed atrophic gastritis in 8 patients (26.6%), intestinal metaplasia in 8 patients (26.6%), lymphoid follicle in 8 patients (26.6%), and dysplasia in 3 patients (10%). The frequency of fundal inflammation, atrophy, intestinal metaplasia, lymphoid follicle, and dysplasia and antral intestinal metaplasia and mild antral dysplasia were found to be higher in those in the pernicious anemia group than in the nonulcer dyspeptic patients. Antral inflammation, atrophy, and moderate and severe antral dysplasia were found to be higher in those in the nonulcer dyspeptic group.
Conclusions. Particularly, fundal precancerous lesions were found to be more frequent in patients with pernicious anemia independent of H. pylori.     

Flow cytometric analysis of the cell cycle in chronic gastritis.

Flow cytometric cell cycle analysis was recorded in gastric biopsy specimens from patients with normal gastric mucosa (GM), superficial gastritis (SG) and chronic atrophic gastritis (CAG). Cell-cycle analysis showed significantly higher percentages of cells in S- and S+G2/M-phase in CAG than in SG and normal GM (P < 0.0001). Moreover, CAG with severe or moderate atrophy showed significantly higher percentages of cells in S-phase (P < 0.05) and S+G2/M-phase (P < 0.02) than CAG with mild atrophy in antrum. In fundus, even if this increase was observed, it did not reach statistical significance. Consideration of concomitant pathologic findings such as oesophagite, gastric or duodenal ulcer, duodenite or benign polyp allowed a better differentiation of CAG both in antrum and in fundus. Significantly higher S-phase was observed in CAG with severe or moderate atrophy than in CAG with mild atrophy (P < 0.05). No statistically significant results were observed in patients with normal gastric mucosa or chronic gastritis and a concomitant pathologic finding.     

Apoptosis in Helicobacter pylori gastritis is related to cagA status

BACKGROUND: Helicobacter pylori infection increases gastric epithelial cell apoptosis; however, the influence of cagA status is still controversial. We aimed to investigate if cagA status is related to apoptosis in H. pylori gastritis at different anatomic sites of the gastric mucosa. MATERIALS AND METHODS: We studied by immunohistochemistry (streptavidin-biotin method) pro-apoptotic (Bax and Bak) and antiapoptotic (Bcl-2 and Bcl-x) proteins expression, scored from 0 to 4, in gastric biopsies, at the antrum (lesser and greater curvatures), incisura, and corpus (greater curvature) from 50 patients with H. pylori gastritis (22 males, 28 females, median age 40 years) and eight non-infected patients (6 males, median age 39.6 years). H. pylori and cagA status were determined by polymerase chain reaction. RESULTS: Apoptotic proteins were expressed in a granular pattern, in the cytoplasm of foveolar cells; Bax and Bak expression was higher than Bcl-2 and Bcl-x in most cases and was significantly higher in patients infected by cagA-positive strains than in those infected by cagA-negative strains (p = .001). Bak expression was higher at the lesser curvature (antrum and incisura) than in the other regions (p = .002) and was correlated with atrophy. Anti-apoptotic proteins were significantly more expressed at the antral lesser curvature than in the other regions of the stomach (Bcl-2: p = .02; Bcl-x: p < .001). CONCLUSIONS: Infection with cagA-positive strains is significantly associated with overexpression of pro-apoptotic proteins in the gastric mucosa, mainly at the antral lesser curvature, which may have a role on atrophy development. Anti-apoptotic proteins were also overexpressed at the lesser curvature, which may occur to keep epithelial cell turnover or might be related to malignant transformation.     

Effect of Omeprazole Therapy on the Survival of Helicobacter pylori, Urease Activity, and Antral Gastric Histology in Patients with Duodenal Ulcer

Background. Helicobacter pylori is associated with chronic active gastritis and peptic ulceration (PU). Omeprazole is a proton pump inhibitor that is effective in healing PU and reducing gastritis. Previously it has been found that omeprazole has some bacteriostatic activity against H. pylori both in vitro and in vivo and in inhibiting urease activity in vitro. Our aim was to evaluate the effect of omeprazole on H. pylori colonization of the gastric mucosa, urease activity in vivo, and the presence of associated gastritis in patients with duodenal ulcer (DU).
Materials and Methods. We studied 12 patients (7 men and 5 women, ages 22–68 yr) with Du larger than 5 mm in diameter with a positive CLOtest (Delta West Ltd., Australia). Omeprazole, 20 mg bid, was given for 8 weeks to each patient, patients were endoscoped at the end of this period to check for healing of DU, and repeat biopsies were obtained from the gastric antrum for histologyical analysis, CLOtest, and culture.
Results. DU healed completely in all patients. Likewise in all patients there was significant reduction in the urease activity, from 22.1=4.17 to 1.58 ± 0.92 units/ml ( p <.001; 95% confidence interval of the difference between means, 32.7–14.1), and reduced H. pylori density, from 1,403.46 ± 128.23 to 422.5 ± 172.39 colony-forming units (CFU) per milligram of tissue biopsy ( p < .001; 95% confidence interval of the difference between means, 1,486.1–590.5). The numbers of H. pylori were reduced on the gastric mucosa after omeprazole therapy and disappeared in six patients, a result that correlated with a negative CLOtest reading after 24 hours.
Conclusion. Omeprazole, 20 mg bid, is capable of reducing H. pylori numbers and urease activity in vivo. There was no significant reduction in the severity of antral gastritis in DU patients studied.     

Experimental Helicobacter pylori infection induces antral-predominant, chronic active gastritis in hispid cotton rats (Sigmodon hispidus)

BACKGROUND: The hispid cotton rat has proven to be an excellent animal model for a variety of human infectious disease agents. This study was performed to evaluate the use of the cotton rat as a model of Helicobacter pylori infection. MATERIALS AND METHODS: Thirty-eight inbred cotton rats were orogastrically inoculated with a human strain of H. pylori. Twenty-eight control cotton rats were dosed with vehicle only. Animals were sacrificed at 2, 4, 12, 26, or 38 weeks after inoculation for bacterial and histologic and immunologic examinations. RESULTS: Helicobacter pylori was cultured from the glandular stomach of 89% of the infected cotton rats. The level of colonization was consistently high (approximately 10(4-6) colony-forming units/g tissue). Histologically, the spiral bacteria were demonstrated on the epithelial surface and in the foveolae of the gastric mucosa with highest numbers in the antrum. H. pylori infection was associated with antral-predominant, chronic active gastritis which progressively increased in severity over time. By week 26 of infection, moderate antral gastritis had developed with frequent involvement of the submucosa and formation of lymphocytic aggregates. Splenic T cells from infected cotton rats expressed mRNAs for interferon-gamma, interleukin-4, interleukin-6, and interleukin-10 following in vitro stimulation with H. pylori. Serum levels of H. pylori-specific immunoglobulin G were significantly elevated after 12 weeks of infection. CONCLUSIONS: The H. pylori-infected cotton rat represents a novel animal model that should prove useful for studies of H. pylori-induced chronic active gastritis and factors affecting gastric colonization by this pathogen.     

Helicobacter pylori modulation of gastric acid

Helicobacter pylori plays major causative roles in peptic ulcer disease and gastric cancer. Elevated acid secretion in patients with duodenal ulcers (DUs) contributes to duodenal injury, and diminished acid secretion in patients with gastric cancer allows carcinogen-producing bacteria to colonize the stomach. Eradication of H. pylori normalizes acid secretion both in hyper-secreting DU patients and hypo-secreting relatives of gastric cancer patients. Therefore, we and others have asked how H. pylori causes these disparate changes in acid secretion. H. pylori gastritis more or less restricted to the gastric antrum in DU patients is associated with increased acid secretion. This is probably because gastritis increases release of the antral acid-stimulating hormone gastrin and diminished mucosal expression of the inhibitory peptide somatostatin. Bacterial products and inflammatory cytokines including TNFalpha may cause these changes in endocrine function. Gastritis involving the gastric corpus tends to diminish acid secretion, probably because bacterial products and cytokines including IL-1 inhibit parietal cells. Pharmacological inhibition of acid secretion increases corpus gastritis in H. pylori-infected subjects, so it is envisaged that gastric hypo-secretion of any cause might become self-perpetuating. H. pylori-associated mucosal atrophy will also contribute to acid hypo-secretion and is more likely in when the diet is high in salt or lacking in antioxidant vitamins. Data on gastric acid secretion in patients with esophagitis are limited but suggest that acid secretion is normal or slightly diminished. Nevertheless, H. pylori infection may be relevant to the management of esophagitis because: (i) H. pylori infection increases the pH-elevating effect of acid inhibiting drugs; (ii) proton pump inhibitors may increase the tendency of H. pylori to cause atrophic gastritis; and (iii) successful eradication of H. pylori is reported to increase the likelihood of esophagitis developing in patients who had DU disease. Points (ii) and (iii) remain controversial and more work is clearly required to elucidate the relationship between H. pylori, acid secretion, gastric mucosa atrophy and esophagitis.     

Chronic gastritis associated with Helicobacter pylori. Correlation between histological and bacteriological findings.

Biopsy specimens of gastric and duodenal mucosa from 326 patients were examined bacteriologically and histologically to determine the correlation between chronic gastritis and H. pylori colonization. H. pylori was identified in 111 (66.5%) patients with evidence of chronic gastritis and in 97 (82.2%) individuals who had gastritis associated with other pathology (gastric o duodenal ulcer, carcinoma o bulboduodenitis). The spiral bacteria was found more frequently in specimens with chronic superficial gastritis (88/107) and no significant difference was observed between the grade of activity of gastritis and H. pylori colonization. Giemsa stain was the most suitable method for detecting H. pylori in histological sections. By electron microscopy the microorganism was seen on the surface of the gastric mucosa, beneath the mucous layer, and more occasionally in intercellular junctions and the gastric pit.     

Inflammatory changes in the gastric mucosa of patients with idiopathic non-ulcer dyspepsia and the effect of colloid bismuth treatment on the course of inflammation]

The studies were aimed at the assessment of the coexistence of non-ulcer dyspepsia with chronic gastritis and Campylobacter pylori infection, and of the effect of therapy with De-Nol on the course of such disease. The studies involved 50 patients with non-ulcer dyspepsia. Prior to and after the treatment with De-Nol samples of the mucosa collected from the antrum and corpus of the stomach have been examined histologically with urease test indicating C. pylori infection. Chronic gastritis of the antral mucosa membrane and/or mucosa of the corpus of the stomach has been found in 36 patients, and normal mucosa in 14 patients. Therapy with De-Nol produced statistically significant improvement. Totally histological improvement has been noted in 77.1% of patients with inflammation of the antral mucous membrane and in 64.3% of patients with inflammation of the corporeal gastric mucosa. Campylobacter pylori has been eradicated in all patients with chronic gastritis. De Nol eliminates or significantly lowers an inflammation in the antrum and/or corpus of the stomach. Its action is related to the eradication of Campylobacter pylori infection.     

Geographic pathology of Helicobacter pylori gastritis

BACKGROUND AND AIM: Helicobacter pylori is etiologically associated with gastritis and gastric cancer. There are significant geographical differences between the clinical manifestation of H. pylori infections. The aim of this study was to compare gastric mucosal histology in relation to age among H. pylori-infected patients from different geographical areas using the same grading system. The prevalence of atrophy and intestinal metaplasia were also compared with the respective gastric cancer incidence in the different countries. METHODS: A total of 1906 patients infected with H. pylori from seven countries were evaluated. Entry criteria included H. pylori positive cases with antral and corpus biopsies between the ages of 18 and 75 years. The minimum number of cases required from a country was 100. Hematoxylin-eosin stained biopsies from antrum and corpus were scored semiquantitatively using the parameters suggested by the Sydney Classification System. Statistical evaluation was performed using Kruskal-Wallis test and Spearman's rank correlation test. RESULTS: The severity of gastric atrophy varied among the different groups with the highest scores being present in Japan. The lowest scores were found in four European countries and in Thailand. The scores for intestinal metaplasia were low in general except for Xi-an, Japan, and Shanghai. For all the countries, the presence of atrophy in the antrum correlated well (r = 0.891) with the incidence of gastric cancer. CONCLUSION: Using a standardized grading system in a large study of H. pylori-related geographic pathology, we found major differences in the overall prevalence and severity of H. pylori gastritis in relation to age. These differences mirrored the respective incidences of gastric cancer in those geographical areas.     

Reactive Nitrogen Species Mediate DNA Damage in Helicobacter pylori-Infected Gastric Mucosa

Background:  Reactive oxygen species (ROS) and reactive nitrogen species (RNS) can play an important role in cellular injury and carcinogenesis of gastric epithelial cells infected with Helicobacter pylori . 8-OH-deoxy guanosine (8-OHdG) and 8-nitroguanine (8-NG) are markers for ROS- and RNS-mediated DNA oxidation, respectively. In this study, RNS-mediated DNA damage in gastric mucosa was observed directly using a newly developed antibody to 8-NG to clarify how H. pylori infection causes nitrative DNA damage to gastric epithelial cells.
Methods:  Immunohistochemistry with anti-8-OHdG and anti-8-NG antibodies was performed on gastric tissue samples from 45 patients (25 men and 20 women) with H. pylori -positive gastritis and 19 patients (11 men and 8 women) exhibiting successful H. pylori eradication. Histologic factors for gastric mucosal inflammation were graded according to the guidelines of the Updated Sydney system.
Results:  In corpus mucosa, 8-OHdG and 8-NG production were significantly associated with the degree of glandular atrophy, infiltration of chronic inflammatory cells and intestinal metaplasia in the glandular epithelial cells. Successful H. pylori eradication resulted in a significant reduction of chronic inflammatory cell infiltration and neutrophilic activity. Mean 8-OHdG production was lower after H. pylori eradication in both corpus and antral mucosa ( p  = .022 and .049, respectively). However, the reduction in 8-NG exhibited was more pronounced than the reduction of 8-OhdG ( p  = .004 and .007, respectively).
Conclusions:  Helicobacter pylori infection can induce inflammatory cells infiltration, which evokes DNA damage of gastric epithelial cells through ROS and RNS production. 8-NG might be a more sensitive biomarker than 8-OHdG for H. pylori -induced DNA damage in gastric mucosa.     

Molecular assessment of c-H-ras p21 expression in Helicobacter pylori-mediated gastric carcinogenesis

Helicobacter pylori (H. pylori) infection plays a significant role in causing gastric cancer; the exact molecular mechanisms of gastric carcinogenesis have not yet been fully determined. Therefore, this study was planned to examine the role of c-H-ras p21 expression in H. pylori infection at different stages of disease progression from precursor lesions to gastric carcinoma. This study was carried out in 200 patients, consisting of normal gastric mucosa (n = 20), mucosa with chronic gastritis (n = 63), intestinal metaplasia (n = 20), dysplasia (n = 11), and gastric adenocarcinoma (n = 86), in which the H. pylori status have been analysed. The expression of c-H-ras p21 was studied at mRNA as well as protein level using RT-PCR and western blotting, respectively. The localization of c-H-ras p21 was also studied semiquantitatively by immunohistochemistry. The RT-PCR and western blotting results of c-H-ras p21 mRNA and protein expressions were significantly increased in chronic gastritis, intestinal metaplasia, dysplasia, and gastric adenocarcinoma patients, respectively. Immunohistochemical study also showed the increased expression of c-H-ras p21 in the similar way. Overexpression of c-H-ras p21 might be due to H-ras mutation at codon 12 of ras gene family in H. pylori infection. The rate of expression of ras p21 was higher in the H. pylori-infected precursor lesions, chronic gastritis 49/56 (87.5%), intestinal metaplasia 16/17 (94%), and dysplasia 9/11(82%) whereas in the case of H. pylori negative cases these groups, show 12.5, 5.9, and 18.2%, respectively. The data suggested that H. pylori infection may increase the expression of c-H-ras p21 early in the process of gastric carcinogenesis.     

Benign epithelial gastric polyps--frequency,location, and age and sex distribution

Prospective investigation has been undertaken with the aim to study the frequency, location and age and sex distribution of various histological types of benign gastric epithelial polyps. Histological type--adenomatous, hyperplastic and fundic gland polyps--was diagnosed on the basis of at least three histological samples taken from the polyp. Biopsy samples were also taken from the antrum and the body of the stomach so that gastritis could be graded and classified, and the presence of H. pylori could be determined by histology. All 6,700 patients, who had undergone upper gastrointestinal endoscopy in a one-year period, participated in this study. Among them 42 benign gastric epithelial polyp were found in 31 patients: adenomatous gastric polyps in 7 patients, hyperplastic gastric polyp in 21 and fundic gland polyp in 3 patients. All patients with hyperplastic polyps had chronic active superficial gastritis, whereas most of the patients with adenomatous polyps had a chronic atrophic gastritis with high prevalence of intestinal metaplasia. Among 21 patients with hyperplastic gastric polyps, 16 (76%) patients were positive for H. pylori infection in contrast to only 2 patients (29%) with adenomatous gastric polyps and 1 patient (33%) with fundic gland polyp. Presented data indicates that hyperplastic gastric polyps are the most common and they are associated with the presence of chronic active superficial gastritis and concomitant H. pylori infection. Adenomatous polyps are rarer and they tend to be associated with chronic atrophic gastritis and intestinal metaplasia. Fundic gland polyp is the rarest type of gastric polyps.     

Increased cell proliferation in chronic Helicobacter pylori positive gastritis and gastric carcinoma--correlation between immuno-histochemistry and Tv image cytometry.

BACKGOUND: Epithelial cell proliferation activity has been reported both to be unaltered and increased in Helicobacter pylori (H. pylori) associated chronic gastritis. The proliferation rate decreased following H. pylori eradication, but results are controversial whether this change is dependent on the success of eradication. We compared the cell proliferation activity of H. pylori positive and negative gastric epithelial biopsies in chronic gastritis with and without intestinal metaplasia (IM) and gastric cancer by the expression of proliferation cell nuclear antigen (PCNA) and Tv image cytometry, and assessed the effect of H. pylori eradication on the cell proliferation rate in the gastric epithelium. METHODS: Brush smears and antral biopsies were taken from 70 patients (42 men, 28 women, mean age 58+/-15 y.o.) on routine endoscopy. Patients were divided into four groups according to the histology; normal epithelia (n = 10), chronic gastritis without IM (n = 24), chronic gastritis with IM (n = 20), and gastric carcinoma (n = 16). Thirty-three patients were H. pylori positive, and success of eradication was controlled in 24 cases. Cell proliferation was measured by immunohistochemistry using PCNA labeling index (LI) and by Tv image cytometry evaluating 12 morpho- and densitometric parameters of each nuclei and 6 additional parameters of each smear. RESULTS: PCNA LI, DNA index and S + G2 ratio were all higher in chronic gastritis than in the normal epithelium, and were further increased in carcinoma. The lower PCNA LI observed in chronic gastritis with IM corresponds to the lower S phase ratio determined by Tv image analysis. In H. pylori positive cases, the proliferation activity was 69.3+/-13.05% prior to the eradication and it decreased to 55.8+/-23.31% after the successful eradication therapy. When immunohistochemistry was compared with Tv image cytometry, PCNA LI significantly correlated with the percentage of cells in GL phase (r = -0.415) and S phase (r = 0.385), Integrated Optical Density mean (r = 0.598), density maximum (r'= 0.608), surface (r = 0.670), layers (r = 0.638), diameter minimum (r = 0.619), diameter maximum (r = 0.730) and perimeter (r = 0.501), respectively (p < 0.05). CONCLUSIONS: Epithelial cell turnover is increased in chronic gastritis with or without IM, and in gastric carcinoma. The lower PCNA LI observed in chronic gastritis with IM corresponds to the lower S phase ratio determined by Tv image analysis. Cell proliferation decreases after successful H. pylori eradication. Both methods proved to be reliable for the determination of epithelial cell proliferation.     

Prevalence of CagA, VacA Antibodies in Symptomatic and Asymptomatic Children with Helicobacter pylori Infection

Background. Limited data are available on the prevalence of CagA and VacA Helicobacter pylori antibodies in children. The aim of this study was to investigate the antibody prevalence to the H. pylori virulence factors CagA and VacA in symptomatic and asymptomatic children with H. pylori infection and to correlate these antibodies with the severity of gastric inflammation or density of H. pylori organisms in the gastric mucosa.
Materials and Methods. Twenty-three symptomatic children and 132 asymptomatic children with positive H. pylori serology participated in this study. Anti– H. pylori IgG antibody and CagA or VacA H. pylori antibodies were measured by enzyme immunoassay (HM-CAP; sensitivity and specificity> 90%) and Western immunoblot (Helicoblot 2.0) methods, respectively. Gastric inflammation and H. pylori density were graded histologically using the revised Sydney criteria.
Results. The prevalence of CagA and VacA antibodies were 69% and 35% in symptomatic children and 54% and 52% in asymptomatic children, respectively. Multiple regression analysis showed a correlation between CagA antibody and the severity of gastritis but no correlation with other histological features, including the number of neutrophils or lymphoid follicles. Neither antibody correlated with the degree of bacterial density in the gastric mucosa.
Conclusion. CagA and VacA H. pylori antibodies are common in the pediatric population. The combined CagA/VacA antibodies correlated weakly with the degree of mucosal inflammation.     

Antigenic Mimicry Between Helicobacter pylori and Gastric Mucosa: Failure to Implicate Heat-Shock Protein Hsp60 Using Immunoelectron Microscopy

Background. Helicobacter pylori infection induces autoantibodies that cross-react with human gastric mucosa from infected individuals. Candidates for the antigens responsible for molecular mimicry causing autoreactivity include the heat-shock protein HspB (Hsp60, sometimes called Hsp54) or Lewis x and Lewis y carbohydrate antigens.
Objective. Our goal was to investigate the involvement of HspB (Hsp60) in autoreactivity between H. pylori and gastric biopsy tissue.
Materials and Methods. Immunoelectron microscopy was used to study cross-reactivity among biopsy tissues from a patient with gastritis, gastric ulcer, and duodenal ulcer and his own serum as well as reactivity with serum raised against HspB from H. pylori and monoclonal antibodies against Lewis antigens.
Results. The patient serum reacted with gastric mucosa, and the antibodies involved were predominantly IgG. Antibody raised to H. pylori HspB (Hsp60) reacted only with H. pylori cells but not with gastric mucosal tissue. In contrast, monoclonal antibodies specific for Lewis x and Lewis y antigens reacted with both H. pylori and human gastric epithelial tissue.
Conclusions. Hsp60 (Hsp54) is unlikely to be involved in autoreactivity seen in individuals infected with H. pylori. In contrast, we could not rule out the role of Lewis x and Lewis y carbohydrate antigens, expressed as a component of H. pylori lipopolysaccharides, in molecular mimicry and autoantibody production.     

Effect of Helicobacter pylori infection on the expression of DNA mismatch repair protein

BACKGROUND: Helicobacer pylori infection is a major gastric cancer risk factor. Deficient DNA mismatch repair (MMR) caused by H. pylori may underlie microsatellite instability (MSI) in the gastric epithelium and may represent a major mechanism of mutation accumulation in the gastric mucosa during the early stages of H. pylori-associated gastric carcinogenesis. In this study, we examined the expression of DNA MMR protein (hMLH1 and hMSH2) in patients with chronic H. pylori infection before and after eradication of the infection. MATERIALS AND METHODS: Gastric tissue samples were collected from 60 patients with H. pylori gastritis and peptic ulcer disease before and after eradication of the infection. The DNA MMR protein expression (hMLH1 and hMSH2) was determined by immunohistochemical staining in 60 patients before and after H. pylori eradication. The percentage of epithelial cell nuclei and intensity of staining were then compared in gastric biopsies before and after eradication. RESULTS: The percentage of hMLH1 (76.60 +/- 20.27, 84.82 +/- 12.73, p=.01) and hMSH2 (82.36 +/- 12.86, 88.11 +/- 9.27, p<.05) positive epithelial cells significantly increased in 53 patients who became H. pylori-negative after eradication therapy. However, the intensity of hMLH1 and hMSH2 staining was not significantly different. In those 7 patients, who did not respond to the eradication therapy and were still H. pylori-positive, the percent positivity and intensity of hMLH1 and hMSH2 staining did not change. CONCLUSIONS: The expression of DNA MMR proteins increased in the gastric mucosa after H. pylori eradication, indicating that H. pylori gastritis may be associated with a reduced DNA MMR system during infection. The effect of H. pylori infection on MMR protein expression appears to be at least partially reversible after H. pylori eradication. These data suggest that H. pylori gastritis might lead to a deficiency of DNA MMR in gastric epithelium that may increase the risk of mutation accumulation in the gastric mucosa cells during chronic H. pylori infection.     

Helicobacter pylori Infection, Gastritis, and the Temperature of Choice for Hot Drinks

Background. The role of the temperature of the diet as a potential etiological factor for gastritis or peptic ulcer disease has been postulated since the beginning of the century. Animal studies have demonstrated damage to gastric mucosa caused by hot water at 60 to 80°C. In the pre- Helicobacter pylori era it was reported that the majority of ulcer patients preferred hot drinks. It also was reported that the temperature of choice for drinks increased with severity of histological grade of gastritis. We evaluated the association between the preferred temperature of hot drinks and the presence of H. pylori infection.
Methods. We tested the temperature of choice for hot drinking liquids among 12 H. pylori -negative and 43 H. pylori -positive volunteers. We also compared the effect of H. pylori therapy on hot drink temperature preference and, in 32 individuals, whether there was a relation between temperature and the degree of gastric atrophy.
Results. There was no difference in the preferred temperature for hot drinks between those volunteers with and without H. pylori infection (63.4°± 6°C compared to 61.3°± 7°C, respectively) (mean ± 1 SD, p =.3) There was no change in preferred temperature after successful therapy of the H. pylori infection compared to unsuccessful H. pylori therapy, nor was there a correlation between the preferred temperature and the presence, absence, or degree of gastric atrophy ( r ² < 0.001).
Conclusion. The temperature of preference for hot drinks was not influenced by H. pylori infection or by the presence of atrophic gastritis.