Helicobacter pylori infection and gastric carcinoma: Not all the strains and patients are alike

Gastric carcinoma (GC) develops in only 1%-3% of Helicobacter pylori (H. pylori) infected people. The role in GC formation of the bacterial genotypes, gene polymorphisms and host's factors may therefore be important. The risk of GC is enhanced when individuals are infected by strains expressing the oncoprotein CagA, in particular if CagA has a high number of repeats containing the EPIYA sequence in its C'-terminal variable region or particular amino acid sequences flank the EPIYA motifs. H. pylori infection triggers an inflammatory response characterised by an increased secretion of some chemokines by immunocytes and colonised gastric epithelial cells; these molecules are especially constituted by proteins composing the interleukin-1beta (IL-1 beta) group and tumour necrosis factor-alpha (TNF-alpha). Polymorphisms in the promoter regions of genes encoding these molecules, could account for high concentrations of IL-1 beta and TNF-alpha in the gastric mucosa, which may cause hypochlorhydria and eventually GC. Inconsistent results have been attained with other haplotypes of inflammatory and anti-inflammatory cytokines. Genomic mechanisms of GC development are mainly based on chromosomal or microsatellite instability (MSI) and deregulation of signalling transduction pathways. H. pylori infection may induce DNA instability and breaks of double-strand DNA in gastric mucocytes. Different H. pylori strains seem to differently increase the risk of cancer development run by the host. Certain H. pylori genotypes (such as the cagA positive) induce high degrees of chronic inflammation and determine an increase of mutagenesis rate, oxidative-stress, mismatch repair mechanisms, down-regulation of base excision and genetic instability, as well as generation of reactive oxygen species that modulate apoptosis; these phenomena may end to trigger or concur to GC development

Helicobacter pylori Infection and Autoimmune Thyroid Diseases: The Role of Virulent Strains

Aim: To verify a possible association between overall H. pylori and CagA+ H. pylori infection and autoimmune thyroid diseases (AITDs). Methods: Consecutive patients with AITDs admitted to one single centre of Endocrinology during one solar year were examined. The diagnoses were Hashimoto thyroiditis (HT) in 76, Graves’ Disease (GD) in 39, and aspecific thyroiditis (AT) in 44 patients. Controls were 136 individuals without AITDs. Median values of fT3, fT4, anti-thyreoglobulin (Tg) antibodies, IL-1β, IL-6, and TNF-α in patients were compared with those in controls. H. pylori infection and CagA status were determined serologically. Structural homology of some thyroid proteins with H. pylori antigens was investigated. Results: H. pylori infection prevalence was significantly increased in GD (66.6%) and HT (64.4%) patients, vs. 29.4% of controls and 34.0% of AT. CagA seropositivity was significantly more frequent in GD (46.1%) and HT (46.9%) infected patients, vs. infected controls (20%). fT3 and fT4 median values were significantly decreased in infected CagA+ GD patients vs. uninfected GD patients. IL-1β median values were increased in patients respect to controls, independently of the clinical form of AITD. Median values of IL-6, TNF-α and anti-Tg autoantibodies in CagA infected patients were significantly higher than those measured in infected CagA− and uninfected patients and in infected CagA+ controls. The examined thyroid proteins shared putative conserved domains with numerous bacterial antigens. Conclusions: Overall H. pylori and CagA+ H. pylori infection were associated with GD and HT, putatively through an increased inflammatory status and molecular mimicry

Cross-sectional study: CagA-positive Helicobacter pylori infection, acute coronary artery disease and systemic levels of B-type natriuretic peptide

Background B-type natriuretic peptide (BNP) determination is routinely used to evaluate the severity of congestive heart failure, a possible consequence of coronary artery disease (CAD). CAD originates from vascular atherosclerotic processes and is stimulated by inflammatory events, which may also be triggered by chronic bacterial infections. Aim To explore the effect of Helicobacter pylori infection upon systemic BNP, tumour necrosis factor-a (TNF-alpha) and interleukin-6 (IL-6) levels and linear homology between cardiac peptides and H pylori. Methods A group of 103 consecutive patients with a diagnosis of non-ST elevation acute CAD (ACAD) and no other concomitant pathology was examined. BNP was measured by a commercial solid-phase sandwich immunoradiometric assay. H pylori infection, CagA serological status and circulating levels of IL-6 and TNF-alpha, were determined by ELISA assays. Amino acid sequence homology between human cardiac and H pylori peptides was investigated by Basic Local Alignment Search Tool (BLAST) analysis. Results Circulating levels of BNP and IL-6, in pg/mL (interquartile difference), among infected patients with anti-CagA serum antibodies, respectively 781 (1899) and 37.7 (137.6), were significantly increased in respect to those measured in uninfected patients, respectively 325 (655) and 7.7 (23.5), (p<0.01 and p=0.025), and, with regard to BNP alone, also in patients infected by CagA negative H pylori strains, 305 (593), (p<0.01). TNF-a levels were raised in CagA positive in respect to uninfected patients. Tropomyosin and Ca2+ transporting ATPases showed strong similarities to H pylori proteins, suggesting the existence of molecular mimicry phenomena. Conclusions Chronic infection by H pylori expressing CagA correlates with high circulating levels of BNP and IL-6 in patients with ACAD

Helicobacter pylori infection and infertility.

OBJECTIVE: To determine (1) the prevalence of Helicobacter pylori infection in male and female patients with reproductive disorders and controls; (2) the presence of anti-H. pylori antibodies in samples of follicular fluid, vaginal secretions and sperm; and (3) the existence of a structural homology between a major spermatozoa protein, tubulin, and H. pylori proteins. PATIENTS AND METHODS: Serum samples from 167 patients with infertility and 837 age- and gender-matched controls (blood donors) were examined by enzyme-linked immunosorbent assay (ELISA) and Western blotting to determine the seropositivity for H. pylori infection. The presence of anti-H. pylori antibodies in samples of follicular fluid, vaginal secretions and sperm was determined using the same techniques. The possible cross-reactivity with spermatozoa of anti-H. pylori hyperimmune sera and human antibodies was studied by immunofluorescence. The N-acid homology of human tubulin with the principal H. pylori proteins was assayed by the WU-blastp program available on the Internet. RESULTS: The prevalence of infection was significantly higher in patients than controls (49.1% v. 33.5%, P < 0.001). Follicular fluids from infected patients contained specific antibodies in all cases, sperm samples in about 50% of cases, and vaginal secretions in a minority of cases. Sera to H. pylori whole antigens and VacA reacted with the tails and the pericentriolar area of human spermatozoa (which are rich in tubulin); sera to urease and heat-shock protein (Hsp) did not. Follicular fluids with anti-H. pylori antibodies immune reacted with spermatozoa. A linear homology was found between beta-tubulin and three H. pylori proteins, flagellin, VacA and CagA. CONCLUSIONS: H. pylori infection may increase the risk of developing reproductive disorders or worsen the clinical expression of this syndrome