Helicobacter pylori and autoimmune disease: Cause or bystander.
ABSTRACT Helicobacter pylori (H. pylori) is the main cause of chronic gastritis and a major risk factor for gastric cancer. This pathogen has also been considered a potential trigger of gastric autoimmunity, and in particular of autoimmune gastritis. However, a considerable number of reports have attempted to link H. pylori infection with the development of extra-gastrointestinal autoimmune disorders, affecting organs not immediately relevant to the stomach. This review discusses the current evidence in support or against the role of H. pylori as a potential trigger of autoimmune rheumatic and skin diseases, as well as organ specific autoimmune diseases. We discuss epidemiological, serological, immunological and experimental evidence associating this pathogen with autoimmune diseases. Although over one hundred autoimmune diseases have been investigated in relation to H. pylori, we discuss a select number of papers with a larger literature base, and include Sjögrens syndrome, rheumatoid arthritis, systemic lupus erythematosus, vasculitides, autoimmune skin conditions, idiopathic thrombocytopenic purpura, autoimmune thyroid disease, multiple sclerosis, neuromyelitis optica and autoimmune liver diseases. Specific mention is given to those studies reporting an association of anti-H. pylori antibodies with the presence of autoimmune disease-specific clinical parameters, as well as those failing to find such associations. We also provide helpful hints for future research.
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ABSTRACT: Prior reports suggested that infection with Helicobacter pylori was associated with respiratory diseases; pathogenetic mechanisms however, were not defined. We tested the hypothesis that VacA, an exotoxin of Helicobacter pylori, a gastric pathogen, was aspirated into the lung and could stimulate secretion of inflammatory cytokines by lung epithelial cells. The presence of VacA was determined by immunohistochemistry in surgical lung biopsy tissue samples from 72 patients with interstitial pneumonia. The effects of VacA on A549 human alveolar epithelial adenocarcinoma cells and normal human bronchial epithelial cells were determined. After incubation with VacA, the secretions of cytokines were measured by Multiplex Luminex® Assays. VacA was detected with anti-VacA antibodies in bronchial epithelial cells and alveolar epithelial cells from 10 of 72 patients with interstitial pneumonia. VacA was more prevalent in lungs of patients with collagen vascular disease-associated interstitial pneumonia than in those of patients with idiopathic pulmonary fibrosis, nonspecific interstitial pneumonia and cryptogenic organizing pneumonia. Incubation of A549 cells and normal human bronchial epithelial cells with VacA for 24 h was cytotoxic, and resulted in vacuolation. VacA induced interleukin-8 production by A549 cells and normal human bronchial epithelial cells and interleukin-6 production by A549 cells. Based on multiplex screening, interleukin-8 and interleukin-6 were the primary secretory products induced by VacA. Helicobacter pylori VacA is present in human lung and can induce interleukin-8 and interleukin-6 production by human lung cells. VacA could have a role in the pathogenesis of respiratory diseases by its cytotoxic effects and by inducing the secretion of interleukin-8 and interleukin-6 by targeted airway epithelial cells. Copyright © 2015. Published by Elsevier Inc.Biochemical and Biophysical Research Communications 03/2015; 460(3). DOI:10.1016/j.bbrc.2015.03.096 · 2.28 Impact Factor
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ABSTRACT: Recent research has demonstrated that infection with the bacterial pathogen Helicobacter pylori is less common amongst patients with multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system (CNS). We aimed to compare the prevalence of H. pylori amongst MS patients and healthy controls, and also investigated the impact of this infection on an animal model for MS, experimental autoimmune encephalomyelitis (EAE). The H. pylori status of 71 MS patients and 42 healthy controls was determined by serology. Groups of C57BL/6 mice were infected with H. pylori, or given diluent alone as a placebo, prior to inducing EAE. Clinical scores were assessed for all mice, and spleens and spinal cord tissue were harvested. CD4+ T cell subsets were quantified by flow cytometry, and T cell proliferation assays were performed. In MS patients the seroprevalence of H. pylori was half that of healthy controls (p = 0.018). Over three independent experiments, prior H. pylori infection had a moderate effect in reducing the severity of EAE (p = 0.012). In line with this, the antigen-specific T cell proliferative responses of infected animals were significantly reduced (p = 0.001), and there was a fourfold reduction in the number of CD4+ cells in the CNS. CD4+ populations in both the CNS and the spleens of infected mice also contained greatly reduced proportions of IFNγ+, IL-17+, T-bet+, and RORγt+ cells, but the proportions of Foxp3+ cells were equivalent. There were no differences in the frequency of splenic CD4+cells expressing markers of apoptosis between infected and uninfected animals. H. pylori was less prevalent amongst MS patients. In mice, the infection exerted some protection against EAE, inhibiting both Th1 and Th17 responses. This could not be explained by the presence of increased numbers of Foxp3+ regulatory T cells, or T cell apoptosis. This is the first direct experimental evidence showing that H. pylori may provide protection against inflammatory demyelination in the CNS.Frontiers in Microbiology 02/2015; 6(52). DOI:10.3389/fmicb.2015.00052 · 3.94 Impact Factor
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ABSTRACT: AIM: To investigate whether Helicobacter pylori (H. pylori) infection contributes to idiopathic thrombocytopenic purpura (ITP) or iron-deficiency anemia (IDA) onset in gerbils. METHODS: A total of 135 Mongolian gerbils were randomly divided into two groups: an H. pylori infection group and a control group. Both groups were fed the same diet and the same amount of food. Each group was then divided into three subgroups, which were sacrificed at 6, 12, or 18 mo for analysis. At each time point, arterial blood was collected from the abdominal aorta and a complete blood cell count was analyzed in the clinical laboratory in the First Affiliated Hospital of Nanchang University. RESULTS: There were no significant differences in platelet counts (938.00 +/- 270.27/L vs 962.95 +/- 162.56 x 10(9)/L), red blood cell counts (8.11 +/- 1.25/L vs 8.44 +/- 1.48 x 10(12)/L), or hemoglobin levels (136.9 +/- 8.76 g/L vs 123.21 +/- 18.42 g/L) between the control and the H. pylori groups, respectively, at 18 mo. With the exception of the mean corpuscular volume (MCV), all other indicators, including white blood cell counts, hematocrit, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, red blood cell distribution width, mean platelet volume, platelet distribution width, lymphocyte count, and lymphocyte count percentage, showed no significant differences between the control and H. pylori infection groups at each time point. The MCV in the H. pylori infection group (52.32 f/L +/- 2.86 f/L) was significantly lower than the control group (55.63 +/- 1.89 f/L) at 18 mo (P = 0.005), though no significant differences were observed at 6 (54.40 +/- 2.44 f/L vs 53.30 +/- 1.86 f/L) or 12 mo (53.73 +/- 2.31 f/L vs 54.80 +/- 3.34 f/L). CONCLUSION: A single H. pylori infection is insufficient to cause onset of ITP or IDA and other factors may be required for disease onset.World Journal of Gastroenterology 09/2014; 20(34):12308-12. DOI:10.3748/wjg.v20.i34.12308 · 2.43 Impact Factor