Helicobacter pylori and gastric autoimmunity

Host specific T-cell response is critical for the outcome of Helicobacter pylori infection. In genetically susceptible individuals, H. pylori can activate gastric CD4+ Th1 cells that recognize cross-reactive epitopes shared by H. pylori proteins and self H+, K+-ATPase, leading to gastric autoimmunity via molecular mimicry.     

Association of Helicobacter pylori and gastric autoimmunity: A population-based study

Abstract Based on clinical studies, a negative association between Helicobacter pylori and autoimmune corpus gastritis is described. In the present investigation of an unselected population of 1461 adults we can state, however, that there exists a relationship between H. pylori infection and the development of gastric corpus autoimmunity. As confirmation for the gastric autoantibody development through molecular mimicry, a high homology (72% in 25 amino acid overlap) between the beta subunit of H. pylori urease and that of H + K + ATPase, the gastric parietal cell autoantigen, was revealed.     

Helicobacter pylori: Gastric Cancer and Extragastric Intestinal Malignancies

The greatest challenge in Helicobacter pylori-related diseases continues to remain prevention of gastric cancer. New evidence supports the beneficial effect of H.?pylori eradication not only on prevention of gastric cancer but also on the regression of preneoplastic conditions of the gastric mucosa. Concerning early detection of gastric cancer there are still no adequate means and there is urgent need to define appropriate markers, for example, by genome-wide research approaches. Currently, the best available method is the "serologic" biopsy based on pepsinogen I and the pepsinogen I/II ratio for identification of patients with severe gastric atrophy at increased risk for gastric cancer development. The treatment of early gastric cancer by endoscopic techniques can be performed safely and efficiently, but patients need meticulous follow-up for detection of metachronous lesions. In case of advanced disease, laparoscopically assisted surgical procedures are safe and favorable compared to open surgery. Two phase III trials support the role of adjuvant systemic treatment with different regimens. Unfortunately, there is still only slow progress in the development of palliative treatment regimens or modification of the existing therapy protocols. There is accumulating evidence for a role of H.?pylori infection also in colorectal carcinogenesis. Seropositive individuals are at higher risk for the development of colorectal adenomas and consequently adenocarcinomas of this anatomical region. This phenomenon can partly be attributed to the increase of serum gastrin as response to atrophic changes of the gastric mucosa.     

Gastric MALT lymphoma and Helicobacter pylori.

Primary gastric low-grade B-cell lymphomas are neoplastic mimics of mucosa associated lymphoid tissue (MALT) as exemplified by Peyer''s patches in the terminal ileum. Architectural and immunophenotypic properties of the neoplastic cells suggest that they originate from MALT-derived marginal zone B-cells. Paradoxically, the normal human stomach is devoid of organized MALT within which a lymphoma can develop. Lymphoid tissue is acquired in the stomach in response to antigenic stimulation, predominantly associated with Helicobacter pylori infection. Studies of patients with low-grade MALT lymphoma have confirmed a high incidence of H. pylori infection and suggest that the infection predates neoplastic transformation. Certain morphological features of MALT lymphomas suggest that the tumor cells remain responsive to antigen drive. Given the close association between gastric MALT lymphoma and H. pylori, it is possible that this organism provides such a drive. In vitro studies have shown that the tumor cells proliferate in a T-cell-dependent way to the presence of H. pylori. Several studies have now demonstrated that eradication of the organism in patients with low-grade gastric MALT lymphoma can result in regression of the tumor. In cases with a high-grade component, the associated low-grade part may regress, but most high-grade gastric MALT lymphomas are unresponsive to this conservative therapy.     

Helicobacter pylori and Clinical Aspects of Gastric Cancer

In spite of important new insights into the basic mechanisms of gastric carcinogenesis, progress in the management of gastric cancer has been modest. Some modifications in the chemotherapies used for palliation and strategies for downstaging of the disease prior to surgical intervention are noteworthy. The positive experience with endoscopic mucosal resection (EMR) and submucosal dissection (ESD) for treatment of early gastric cancer has been confirmed and extended. The procedure-related morbidity and post-interventional quality of life is clearly favorable compared to open surgical resection in well-selected patients. New data on Helicobacter pylori revealed that eradication after endoscopic resection of early gastric cancer significantly reduces the incidence of recurrent and metachronous gastric neoplasias. It can further improve healing rates of treatment induced gastric ulcers. Eradication therapy therefore remains the best target for prevention of the disease. Critical is the "point of no return" when mucosal alterations (i.e. intestinal metaplasia, glandular atrophy) are no longer reversible. A population-based screen-and-eradicate strategy for H. pylori infection can at present only be recommended in high incidence regions.     

Helicobacter pylori phase variation, immune modulation and gastric autoimmunity

Helicobacter pylori can be regarded as a model pathogen for studying persistent colonization of humans. Phase-variable expression of Lewis blood-group antigens by H. pylori allows this microorganism to modulate the host T-helper-1-cell versus T-helper-2-cell response. We describe a model in which interactions between host lectins and pathogen carbohydrates facilitate asymptomatic persistence of H. pylori. This delicate balance, favourable for both the pathogen and the host, could lead to gastric autoimmunity in genetically susceptible individuals.     

Gastric juice neopterin in Helicobacter pylori infection

Abstract Neopterin, a pteridine compound produced by macrophages activated by interferon-gamma, is widely used to assess the activation of cellular immunity. An elevation in serum or urinary neopterin reflects immune activation in many different disorders, including viral infections, cancer, autoimmune diseases or acute myocardial infarction, but less attention has been paid to neopterin concentration in other biological fluids. The aim of the present study was to examine neopterin concentration in gastric juice. An association with the presence of Helicobacter pylori , a bacterium linked to the most common disorders of upper digestive tract, was also investigated. Gastric juice was obtained at endoscopy from 61 patients. Neopterin was determined by a radioimmunoassay and the presence of H. pylori was examined by urease test. The macroscopic finding of bile in gastric juice was associated with significantly higher neopterin levels compared to patients where no bile was noted (15.5 ± 15.6 vs. 2.1 ± 3.0 nmol/l, P < 0.001). However, similar concentrations were observed in the H. pylori positive and H. pylori negative patients (7.6 ± 12.0 vs. 11.1 ± 14.9 nmol/l). Even in the absence of macroscopic bile contamination, no significant difference could be found between the infected and uninfected patients (2.3 ± 3.2 vs. 1.3 ± 1.9 nmol/l), and the patients with duodenal ulcer and normal findings (3.8 ± 4.6 vs 1.6 ± 1.9 nmol/l). The contamination of gastric juice with bile represents the limitation for the use of neopterin as a marker of immune activation in the gastric mucosa. Rather than an index of immune activation, gastric juice neopterin concentration represents a marker of duodenogastric reflux.     

Early events in lupus humoral autoimmunity suggest initiation through molecular mimicry

The origins of autoimmunity in systemic lupus erythematosus (SLE) are thought to involve both genetic and environmental factors. To identify environmental agents that could potentially incite autoimmunity, we have traced the autoantibody response in human SLE back in time, prior to clinical disease onset, and identified the initial autoantigenic epitope for some lupus patients positive for antibodies to 60 kDa Ro. This initial epitope directly cross-reacts with a peptide from the latent viral protein Epstein-Barr virus nuclear antigen-1 (EBNA-1). Animals immunized with either the first epitope of 60 kDa Ro or the cross-reactive EBNA-1 epitope progressively develop autoantibodies binding multiple epitopes of Ro and spliceosomal autoantigens. They eventually acquire clinical symptoms of lupus such as leukopenia, thrombocytopenia and renal dysfunction. These data support the hypothesis that some humoral autoimmunity in human lupus arises through molecular mimicry between EBNA-1 and lupus autoantigens and provide further evidence to suspect an etiologic role for Epstein-Barr virus in SLE.     

Invasiveness of Helicobacter pylori into Human Gastric Mucosa

Background. Helicobacter pylori has generally been observed only in the gastric mucous layer or in the spaces between gastric mucus -s ecreting cells and not in the gastric epithelial cells or in the lamina propria. The purpose of this study is to determine whether H. pylori invades the gastric mucosa, using an immunoelectron microscopical examination of human gastric mucosa infected with H. pylori.
Materials and Methods. Five hundred gastric antral biopsy specimens were fixed in a periodate-lysin-paraformaldehyde solution, embedded in Lowicryl, sectioned, and examined with a light microscope. One hundred specimens moderately or severely infected with H. pylori were selected and were incubated with polyclonal rabbit anti– H. pylori antibody. The specimens were washed, incubated with 20 nm of colloidal gold–conjugated goat anti–rabbit IgG, stained with uranyl acetate and lead citrate, and observed with a transmission electron microscope.
Results. In one case, a bacterium was observed within the cytoplasm of a gastric mucus -s ecreting cell; in another case, a few bacteria were observed within the cytoplasm of a stromal cell in the lamina propria. The bacteria could be differentiated from degenerated intracellular organelles by gold particles attached to the bacteria.
Conclusion. H. pylori rarely invade the lamina propria and gastric cells.     

Helicobacter pylori: molecular evolution of a bacterial quasi-species

Helicobacter pylori persists chronically within individuals and as they spread the mutating bacteria migrate with them. The continuous selection and microevolution generates a population of closely related but different bacteria that behave like a quasi-species. Within this heterogeneity, H. pylori strains fall into distinct types, into the virulent (type I) and less virulent (type II) strains, based on the presence of a pathogenicity island (cag) that encodes a specialized secretion machinery. We propose that during chronic infection a dynamic equilibrium between bacteria expressing a disparate degree of virulence is established, and that diverse forms prevail at different times.