Riccardo Negrini

Helicobacter pylori infection induces antibodies cross-reacting with human gastric mucosa

The authors previous observation that many of the monoclonal antibodies against Helicobacter pylori cross-react with the cells of the human gastric mucosa prompted them to investigate the possibility that gastric self-antigens cross-reacting with H. pylori could be involved in the immune response against this organism. It was found that three antibodies against H. pylori, CB-4, CB-10, and CB-14, that cross-react with the human gastric mucosa also intensely cross-reacted with murine gastric epithelial cells. A strong reaction against autologous mucosa was also evident in the sera of mice immunized with H. pylori but not with other bacteria. A serological study performed in a group of 82 patients undergoing gastroscopy showed that the presence of seropositivity against H. pylori was strongly correlated with the presence of autoantibodies against human antral gastric mucosa. This activity was neutralized after absorption of the sera with H. pylori but not with other gram-negative bacteria. The antibodies in the mouse and in the human did not react with other segments of the gastrointestinal tract or with most of the other organs. Mice bearing hybridomas secreting a cross-reacting antibody (CB-4) had histopathologic abnormalities in their stomachs. These lesions were absent in the stomachs of mice bearing hybridomas secreting a non-cross-reacting antibody (CB-26). It was concluded that H. pylori infection can stimulate antibodies cross-reacting with gastric autoantigens and that this immunologic mechanism may represent a pathogenic link between H. pylori and gastritis.

The gastric H+,K+-ATPase is a major autoantigen in chronic Helicobacter pylori gastritis with body mucosa atrophy ☆ ☆☆ ★ ★★

BACKGROUND & AIMSnA subgroup of Helicobacter pylori-infected patients develops autoantibodies to gastric parietal cell canaliculi. The aim of this study was to define the unknown autoantigen.nnnMETHODSnWe screened 72 H. pylori-infected patients, 5 patients with autoimmune gastritis, and 36 healthy controls for immunoglobulin G autoantibodies to canaliculi by immunohistochemistry. The antigen specificity was determined by immunoprecipitation of the murine gastric H+,K+-adenosine triphosphatase (H+,K+-ATPase) expressed in oocytes and by immunoblotting on human gastric membranes from the body mucosa.nnnRESULTSnAutoantibodies specific for the conformational peptides of the H+,K+-ATPase were detected in 3% (1/36) of controls, in all patients with autoimmune gastritis (5/5), in 25% (18/72) of H. pylori-infected patients, and in 47% (15/32) of the infected patients with anticanalicular autoantibodies. No other major autoantigen was identified. Atrophy in the gastric body mucosa was found in 60% (9/15) of infected patients with both anticanalicular and anti-H+,K+-ATPase antibodies, but only in 13% (5/37) of infected patients lacking both autoantibodies (P < 0.01).nnnCONCLUSIONSnThe gastric H+,K+-ATPase is a major autoantigen in H. pylori-associated antigastric autoimmunity. Thus, anti-H+,K+-ATPase autoantibodies, which are closely linked to classical autoimmune gastritis, are also significant indicators for body mucosa atrophy in chronic H. pylori gastritis.

Two-thirds of Atrophic Body Gastritis Patients Have Evidence of Helicobacter pylori Infection

Helicobacter pylori is involved in the induction of atrophic body gastritis (ABG). During the progression of atrophic gastritis the disappearance of H. pylori has been documented and in time serology is the only sign that indicates a previous infection. It has been shown that a positive serology, in ABG patients without histological evidence of infection, indicates an active H. pylori infection.

Autoantibodies to Gastric Mucosa in Helicobacter pylori Infection

Although Helicobacter pylori is recognized as the main cause of chronic gastritis and its associated diseases, very little is known about the pathogenetic mechanisms leading to intestinal metaplasia and atrophic gastritis.

Phase variation in H type I and lewis a epitopes of Helicobacter pylori lipopolysaccharide

ABSTRACT Helicobacter pylori NCTC 11637 lipopolysaccharide (LPS) expresses the human blood group antigens Lewis x (Lex), Ley, and H type I. In this report, we demonstrate that the H type I epitope displays high-frequency phase variation. One variant expressed Lex and Ley and no H type I as determined by serology; this switch was reversible. Insertional mutagenesis in NCTC 11637 of JHP563 (a poly(C) tract containing an open reading frame homologous to glycosyltransferases) yielded a transformant with a serotype similar to the phase variant. Structural analysis of the NCTC 11637 LPS confirmed the loss of the H type I epitope. Sequencing of JHP563 in strains NCTC 11637, an H type I-negative variant, and an H type I-positive switchback variant showed a C14 (gene on), C13 (gene off), and C14 tract, respectively. Inactivation of strain G27, which expresses Lex, Ley, H type I, and Lea, yielded a transformant that expressed Lex and Ley. We conclude that JHP563 encodes a β3-galactosyltransferase involved in the biosynthesis of H type I and Lea and that phase variation in H type I is due to C-tract changes in this gene. A second H type I-negative variant (variant 3a) expressed Lex and Lea and had lost both H type I and Leyexpression. Inactivation of HP093-HP094 resulted in a transformant expressing Lex and lacking Ley and H type I. Structural analysis of a mutant LPS confirmed the serological data. We conclude that the HP093-HP094 α2-fucosyltransferase (α2-FucT) gene product is involved in the biosynthesis of both Ley and Lex. Finally, we inactivated HP0379 in strain 3a. The transformant had lost both Lex and Leaexpression, which demonstrates that the HP0379 gene product is both an α3- and an α4-FucT. Our data provide understanding at the molecular level of how H. pylori is able to diversify in the host, a requirement likely essential for successful colonization and transmission.

Role of Helicobacter pylori infection in pernicious anaemia

BACKGROUNDnPernicious anaemia is associated with atrophic body gastritis and considered an autoimmune disease. Whether Helicobacter pylori is involved in the induction of pernicious anaemia is uncertain.nnnAIMSnTo investigate the prevalence of Helicobacter pylori infection in pernicious anaemia patients and to ascertain whether the Helicobacter pylori-positive patients had distinctive clinical and gastric morphofunctional characteristics.nnnPATIENTS AND METHODSnA series of 81 consecutive pernicious anaemia patients underwent serological, functional and endoscopic/histological investigations.nnnRESULTSnA total of 49 (60.5%) patients were Helicobacter pylori-positive (males 61.2% vs females 38.8%). No difference was observed in clinical and morphofunctional characteristics between Helicobacter pylori-positive and negative patients, whereas distinctive functional/histological features between histologically Helicobacter pylori-positive (n=8) and serologically Helicobacter pylori-positive (n=41) cases were detected. In the histologically Helicobacter pylori-positive group, Pepsinogen I was higher [13 (058) vs 5 (0-26) ng/ml; p=0.0025)] and positivity for anti-parietal cell antibodies was lower [42.9% vs 76.9, p=0.0867]. Antral histological variables of the gastritis score were significantly higher in the histologically Helicobacter pylori-positive than in the serologically Helicobacter pylori-positive patients, but this latter group had a higher score of body atrophy (2.63+/-0.12 vs 1.71+/-0.29; p=0.0051). Body inflammation was also significantly higher in the histologically Helicobacter pylori-positive group (chronic inflammation: 1.43+/-0.2 vs 1.05+/-0.06; p=0.0271; inflammation acitivity: 0. 57+/-0.3 vs 0.15+/-0.06, p=0.0220). Antral mucosa was normal in 24/41 (58.5%) of the serologically Helicobacter pylori-positive patients, but only in 1/8 (12.5%) of the histologically Helicobacter pylori-positive patients (p=0.0232).nnnCONCLUSIONSnAlmost two thirds of pernicious anaemia patients have evidence of Helicobacter pylori, but only those with an active Helicobacter pylori infection have distinctive functional and histological features. These findings support the hypothesis that Helicobacter pylori infection could play a triggering role in a subgroup of pernicious anaemia patients.

Interaction of homocysteine and conventional predisposing factors on risk of ischaemic stroke in young people: consistency in phenotype-disease analysis and genotype-disease analysis

Background and objectives: Whether the association between mild hyperhomocysteinaemia and ischaemic stroke is the consequence of a predisposing genetic background or is due to the confounding influence of established predisposing factors remains to be determined. Methods: Plasma total homocysteine (tHcy) concentration and the distribution of the C677T genotypes of the methylenetetrahydrofolate reductase gene (MTHFR) were compared in 174 consecutive patients with stroke aged <45 years and 155 age and sex-matched controls. The effect of conventional risk factors on the relationship between phenotype-disease and genotype-disease was analysed by two-way and three-way interaction analysis and by the classification and regression trees (CART) model. Results: tHcy concentrations were markedly higher in patients with ischaemic stroke (median 11.9 μmol/l, range 2.0–94.0) than in controls (median 9.8 μmol/l, range 4.7–49.6). An increased risk was also associated with the TT677 genotype (odds ratio (OR) 1.98; 95% confidence interval (CI) 1.04 to 3.78) and with the T allele (1.40; 95% 1.03 to 1.92) of the MTHFR gene. A differential effect of Hcy levels on risk of stroke was observed according to the distribution of environmental–behavioural risk factors, with a stronger influence in the subcategory of people with hypertension and smokers (OR 24.8; 95% CI 3.15 to 196). A comparable environmental-dependent TT677 MTHFR genotype–stroke association was observed in the genotype-disease analysis. Conclusions: A consistency of phenotype-disease analysis and genotype-disease analysis is indicated by analysing specific subcategories of patients, defined by the distribution of established risk factors. The assumption that the Hcy–stroke relationship is unlikely due to a reverse-causality bias is indirectly supported by our data.

Absence of Helicobacter pylori in Dental Plaque Determined by Immunoperoxidase

Attempts to detect Helicobacter pylori in dental plaque have given contrasting results, and the possibility of an oral‐oral transmission of the infection remains unclear. In this study, a sensitive and specific immunoperoxidase method has been employed to assess the presence of H. pylori in dental plaque.

Novel Monoclonal Antibody-Based Helicobacter pylori Stool Antigen Test

Background.u2002 A number of noninvasive tests have been developed to establish the presence of Helicobacter pylori infection. Although polyclonal antibody‐based stool antigen testing has a good sensitivity and specificity, it is less accurate than urea breath testing. Recently, a monoclonal antibody‐based stool antigen test demonstrated an excellent performance in diagnosing H. pylori infection in adults and in pediatric populations.

Immunity markers in patients with Helicobacter pylori infection: effect of eradication

Background.u2002 Helicobacter pylori is a microorganism able to stimulate a robust inflammatory and systemic immune response.