Serum antibodies positivity to 12 Helicobacter pylori virulence antigens in patients with benign or malignant gastroduodenal diseases--cross-sectional study.

AIM: To investigate the association of gastric histological and endoscopic findings in patients with Helicobacter pylori (H. pylori), according to presence of seropositivity to 12 bacterial virulence antigens. METHODS: This is a cross-sectional single-center study of 360 consecutive outpatients referred in the period of one year to upper gastrointestinal endoscopy because of dyspeptic complaints. Patients sera were tested by Western blot method to determine the presence of serum antibodies to bacterial virulence antigens--p120 (CagA--cytotoxin-associated antigen), p95 (VacA - vacuolating cytotoxin), p67 (FSH--flagellar sheath protein), p66 (UreB--urease enzyme heavy subunit), p57 (HSP homologue--heath shock protein homologue), p54 (flagellin), p33, p30 (OMP--outer membrane protein), p29 (UreA--urease enzyme light subunit), p26, p19, and p17. Upper gastrointestinal endoscopy was performed, endoscopic diagnosis recorded, and 4 mucosal biopsy samples were obtained and assessed according to Updated Sydney protocol. RESULTS: The sera of 207 patients were analyzed. Thirty patients had gastric adenocarcinoma, 126 peptic ulcers, and 51 normal finding. p120 (CagA) seropositivity was significantly more often present in patients with higher activity grade in the antrum (P = 0.025), p30 in patients with greater inflammation in the antrum (P = 0.025) and the corpus (P = 0.010), p33 in patients with greater inflammation in the corpus (P = 0.050), and p19 (OMP) in patients with lower intestinal metaplasia grades in the corpus (P = 0.025). Seroreactivity to all other bacterial proteins showed no association with the histological status of the stomach mucosa. Except for the seropositivity to protein p95 (VacA), which was more often present in patients with duodenal ulcer (P = 0.006), there was no difference in seroreactivity to other bacterial proteins and upper gastrointestinal endoscopic findings. CONCLUSIONS: p120 (CagA), p33, p30 (OMP), and p19 (OMP) seropositivity was more often present in patients with higher grades of the histological parameters of gastritis and seropositivity to protein p95 (VacA) with endoscopic presence of duodenal ulcer. Histological parameters of gastritis are more associated with bacterial virulence than endoscopic findings.

Influence of Helicobacter pylori infection persistence on bcl-2 expression in gastric mucosa inflammatory cells.

Chronic Helicobacter (H.) pylori infection is an etiological factor related to gastric adenocarcinoma and gastric mucosa-associated lymphoid tissue (MALT) lymphoma. The expression of bcl-2 protein significantly decreases as the grade of MALT lymphoma advances. The aim of this study was to evaluate bcl-2 expression in inflammatory cells in lamina propria in gastric biopsy samples collected from two groups of patients with chronic gastritis divided on the basis of the success or failure of H. pylori eradication. Sixty-five patients with chronic gastritis were divided into two groups of 45 and 20 patients according to their therapeutic response. The gastric mucosa samples were analyzed histologically in both groups of patients before and after standard therapy (for eradicated, after one therapeutic cycle; and for non-eradicated, after three therapeutic cycles) for H. pylori density, urease activity and bcl-2 expression. In the eradicated group of patients, H. pylori eradication was accompanied by significantly lower grades of bacterial colonization and lower urease activity in the corpus and antrum. Bcl-2 expression in inflammatory cells showed no statistically significant changes in either patient group at either location. There was no between-group difference in bcl-2 expression either. In conclusion, persistent long-lasting H. pylori infection is associated with higher grades of bacterial colonization and higher urease activity but not with bcl-2 expression in inflammatory cells.

Seroprevalence of Helicobacter pylori infection in dyspeptic patients.

The objective of the study was to assess the effect of age on the seroprevalence of Helicobacter (H.) pylori infection in dyspeptic patients. The results obtained in the patient group were compared with findings on the seroprevalence of H. pylori infection in 2051 blood donors. Serum samples were tested by the commercial ELISA and CFT assays according to manufacturer's instructions. The mean seroprevalence of H. pylori infection as determined by ELISA/CFT was 64.0%/51.7% in the group of blood donors and 92.3%/89.5% in the group of dyspeptic patients. Study results indicated a higher prevalence of H. pylori infection in dyspeptic patients as compared with blood donors in all age groups. In the patient S group, H. pylori seroprevalence was not age dependent.

Influence of H. pylori infection and eradication on p53, c-erbB-2 and Ki-67 in gastric mucosa.

BACKGROUND/AIMS: To evaluate the expression of antigens c-erbB-2, p53, and Ki-67 in gastric biopsy, bacteria density and urease activity in two groups of patients with chronic gastritis separated on the basis of the success or failure of H. pylori eradication. METHODOLOGY: Sixty-five patients with chronic gastritis were split in two groups (n=45/20) related to response to the therapy. The gastric mucosa samples (Sydney system) were analyzed histologically in both groups of patients before and after standard therapy (for eradicated, E group after one cycle; for non-eradicated, NE group after three cycles) for H. pylori infection, urease activity, c-erbB-2, p53 and Ki-67 expression. Sera samples taken before and after treatment were also analyzed for specific antibody against H. pylori. RESULTS: The eradication of H. pylori in patients of the E group was accompanied with significant lower colonization grades of bacteria, urease activity, proliferating rate, p53, and Ki-67 expression while c-erbB-2 expression was unchanged. In the NE group, all parameters were the same before and after therapy with exception of p53, which was slightly higher on both locations. Strong expression of c-erbB-2 in corpus of the NE group was determinate. Serum activity of specific antibodies against H. pylori was lower after the therapy in both groups of patients, but in the eradicated group this change was much stronger that in the non-eradicated. CONCLUSIONS: Long persisting infection is related with higher colonization grades of bacteria, urease activity, p53, c-erbB-2 and Ki-67 expression. Changes of those markers are connected with duration of infection and location where these changes were obtained.

The place and role of serologic methods in detecting Helicobacter pylori infection.

The aim of the study was to determine the place and role of serologic methods in detecting Helicobacter pylori (H. pylori) infection, on the basis of estimated enzyme-linked immunosorbent assay (ELISA) and complement fixation test (CFT) sensitivity and specificity. A total of 549 patients were included in the study. ELISA and CFT as serologic methods were compared with invasive methods (rapid urease test--CLO test, culture, histology). The sensitivity of serologic methods was above 90%, and their specificity was around 80%. Study results confirmed the value, reliability and usefulness of serologic methods in the detection of H. pylori infection.

[Helicobacter pylori--introduction and review of research]. / Helicobacter pylori--uvod i pregled istrazivanja.

The discovery of Helicobacter pylori has revolutionized the pathophysiological and clinical approach to gastric and duodenal ulcer. Since the first paper identifying H. pylori was published only 17 years ago, it has been found out that this bacterium causes probably the commonest human infection. Numerous papers published so far have confirmed causal relationship between H. pylori infection and gastritis, duodenal ulcer, gastric ulcer and gastric cancer. If any recent achievement in the world of medicine is to be called revolutionary, then it is the discovery of the role of a spiral bacterium in the etiopathogenesis of gastritis, gastric ulcer, duodenal ulcer and gastric cancer. The discovery of the role of Helicobacter pylori has entirely changed our views and approach to the treatment of patients with stomach disorders. Not only do these discoveries change our actions, but above all our way of thinking. Almost routine diagnostics and treatment of gastritis, gastric ulcer or cancer has been replaced by studies in epidemiology, isolation and eradication of a single bacterium.

[Epidemiology of Helicobacter pylori infection]. / Epidemiologija infekcije Helicobacterom pylori.

About 50% of adults in the developed and 80-90% in the developing countries are estimated to be infected by Helicobacter pylori. Being 68% nationally, this rate is higher in the northern continental parts of Croatia, which also have higher gastric cancer rates. Low socio-economic status, poor living conditions in childhood (the age when Helicobacter pylori is typically acquired), and exposure to the stomach content of an infected person are risk factors for Helicobacter pylori. Most of the infected are symptomless, with 10 to 20% subsequently developing the disease, and this mainly from peptic ulcer, asymptomatic chronic gastritis and chronic dyspepsia. Less than 5/10,000 become affected with adenocarcinoma, MALT lymphoma or primary non-Hodgkin's gastric lymphoma. Helicobacter pylori is under intensive study for possible association with other diseases. As transmission route of the infection is still unclear, any mechanism allowing the bacteria entry into a non-infected individual's stomach is probably a possibility. In addition to improved socio-economic status, eradication or vaccination may be contributors to the reduction in the number of the infected.

[Helicobacter pylori--bacterial characteristics]. / Helicobacter pylori--bakterioloske znacajke.

Helicobacter pylori lives in the gastric mucosa of about half of world population. H. pylori is a gram-negative, microaerophilic, facultatively acidophilic rod, very sensitive to drying and usual disinfectants. H. pylori strains show great genetic variability, the main mechanism of this phenomenon being in vivo genetic recombination. The principal virulence factors are: vacuolating cytotoxin, enzyme urease, motility, adhesive molecules on the cell surface, catalase and superoxide-dysmutase, receptor for human lactoferin and factors which promote proinflammatory cytokine secretion. Strains of H. pylori are sensitive to ampicillin and tetracycline; resistance to macrolide antibiotics is 7-15% in different parts of the world, and to metronidazole is 7-50% or even more. Because in vitro sensitivity of H. pylori is the most important factor for successful therapy, it is necessary to monitor this sensitivity continuously in a particular area.

[Diagnosis of Helicobacter pylori infection]. / Dijagnostika infekcije Helicobacterom pylori.

The diagnostics of Helicobacter pylori infection is now one of the most important aspects of the diagnosis of various gastroduodenal diseases. New data have shown that Helicobacter pylori is a causative agent of peptic ulcer disease and an important factor in cancer development. Numerous diagnostic tests are now available. They can be divided into two groups: invasive and noninvasive tests. All invasive test methods are based on endoscopic examination during which biopsy specimens are obtained for direct (histological analysis, isolation) or indirect (urease test) diagnosis of Helicobacter pylori infection. Noninasive methods reveal the presence of Helicobacter pylori by measuring the activity of urease (urea breath test), then by confirming the presence of antibodies in the serum or saliva of the infected person or by confirming the presence of Helicobacter pylori antigens in the feces.

[Helicobacter pylori--bacteriologic diagnosis and antibiotic sensitivity tests]. / Helicobacter pylori--bakterioloska dijagnostika i testiranje osjetljivosti na antibiotike.

Bacteriological diagnosis of Helicobacter pylori consists of culture from gastric biopsies, gastric juice, faeces and from specimens obtained from oral cavity, antigen stool assay and molecular diagnostic methods. In routine work culture is done from gastric biopsies. Other specimens are usually cultivated for research purposes. Culture constitutes the most specific way to establish the diagnosis of H. pylori infection. One of the major advantages of culture is that it allows sensitivity testing to drugs used in therapy. Culture also allows characterisation of H. pylori. Antigen stoll assay is a non-invasive diagnostic procedure, which should be evaluated. Molecular methods have confirmed their potential for epidemiological research and for the detection of resistant H. pylori, especially for macrolides. The clinical settings, local availability and economic considerations should guide use of bacteriological diagnostic methods.

[Serodiagnosis of Helicobacter pylori infection]. / Seroloska dijagnostika infekcije Helicobacterom pylori.

Infection with Helicobacter pylori induces antibodies, but these are not able to eradicate the bacterium from the gastric mucosa. Enzyme linked immunosorbent assay is the laboratory based method and most commonly used to measure qualitatively and quantitatively anti-Helicobacter pylori antibodies of different immunoglobulin classes in almost all infected patients. Quantitative serological tests are useful in the follow-up of eradication therapy. Serology is the method of choice in population studies and in the retrospective analysis of stored serum samples to study the natural course of this chronic infection.

[Helicobacter pylori and malignant diseases of the stomach]. / Helicobacter pylori i maligne bolesti zeluca.

The association between Helicobacter pylori infection and gastric malignancies, cancer and MALT lymphoma, has been suggested through several lines of evidence during the last decade. Although unresolved issues still cast doubts on the real weight of these association, in the sequence of events that leads to gastric cancer or lymphoma, Helicobacter pylori appears to play a prominent role in the very initial steps as causative agent of chronic gastritis. The subsequent events in the sequence--atrophy, intestinal metaplasia, dysplasia and cancer are multifactorial involving environmental agents, host response and characteristics of the bacterial strain itself. Recognition of the causal role of Helicobacter pylori infection in the cancer induction theoretically presents tools for its prevention. The ongoing studies will show in the future whether eradication or prevention of infection are followed by a reduction in risk of cancer. Lymphomas arising from gastric mucosa-associated lymphoid tissue (MALT) may be a clonal evolution starting from the infection. In low-grade gastric MALT lymphoma cure of the infection induces complete remission in the majority of patients. Longer follow-up investigations are necessary to determine if remissions indicate a cure of the disease.

[A vaccine against Helicobacter pylori infection]. / Vakcina protiv infekcije Helicobacterom pylori.

Oral immunization with the urease of Helicobacter pylori was shown to induce protection against Helicobacter felis in mice. The first identification of a protective antigen (urease) was followed by the identification of the protective antigens, such as the heat-shock protein (HspA) and the vacuolating cytotoxin VacA. The final selection of the antigens to be used in a vaccine depends on the conservation of these antigens among Helicobacter pylori strains, their role as virulence factors and conservation of their immunogenic properties when expressed as recombinant proteins. Furthermore, therapeutic immunizations were also effective in eradication of Helicobacter from chronically infected animals. These encouraging results imply that immunization may also be useful in the therapy of Helicobacter pylori infection in humans. In this review, preliminary data and directions for future research on Helicobacter vaccines are described.