Antibody response patterns to Helicobacter pylori infection in a rural Ugandan population cohort.

Background: Helicobacter pylori (H. pylori) establishes life-long infection in humans in the absence of treatment and has been associated with a variety of gastrointestinal conditions including peptic ulcer and gastric cancer. Antibody responses to H. pylori antigens are found to be associated with disease risk, however, data from Africa are scarce. Methods: To assess the seroprevalence of H. pylori and characterise antibody response patterns, we measured serum IgG antibody levels to 14 antigens among 7,211 individuals in a rural Ugandan population cohort. Multivariate-adjusted linear regression models were fitted to investigate the influence of age, sex, and co-infection on antibody seroreactivity levels. Results: H. pylori seroprevalence was 95% in our study population, with 94% of individuals seropositive in childhood (<15 years). In H. pylori positive individuals, we found a markedly high seroprevalence (~99%) and antibody levels to the high-risk antigens CagA and VacA, in addition to Cagδ ;. HSV-2 co-infection was significantly associated with higher IgG levels of CagA and VacA (OR=1.10, 95% C. I=1.05-1.16). HIV infection was associated with lowered IgG levels to CagA (OR=0.86, 95% C.I.=0.80-0.93), and HPV infection was associated with increased IgG levels to VacA (OR=1.16, 95% C.I.=1.11-1.21). Conclusions: H. pylori in this population is ubiquitous from childhood, with a high prevalence and high seroreactivity levels of high-risk antigens, suggesting chronic active inflammatory responses in individuals that are indicative of risk of disease. Further investigation is warranted to fully understand the relationship between host, immunogenicity, and clinical outcomes to better stratify by risk and improve treatment.

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Gastric Microenvironment—A Partnership between Innate Immunity and Gastric Microbiota Tricks Helicobacter pylori

Journal of Clinical Medicine ◽

10.3390/jcm10153258 ◽

2021 ◽

Vol 10 (15) ◽

pp. 3258

Author(s):

Cristina Oana Mărginean ◽

Lorena Elena Meliț ◽

Maria Oana Săsăran

Keyword(s):

Helicobacter Pylori ◽

Immune System ◽

Pathogenic Bacteria ◽

T Regulatory Cells ◽

Inflammatory Responses ◽

Mucosal Barrier ◽

Pathogen Recognition ◽

Microenvironmental Factors ◽

H Pylori ◽

Major Factors

Helicobacter pylori (H. pylori) carcinogenicity depends on three major factors: bacterial virulence constituents, environmental factors and host’s genetic susceptibility. The relationship between microenvironmental factors and H. pylori virulence factors are incontestable. H. pylori infection has a major impact on both gastric and colonic microbiota. The presence of non-H. pylori bacteria within the gastric ecosystem is particularly important since they might persistently act as an antigenic stimulus or establish a partnership with H. pylori in order to augment the subsequent inflammatory responses. The gastric ecosystem, i.e., microbiota composition in children with H. pylori infection is dominated by Streptoccocus, Neisseria, Rothia and Staphylococcus. The impairment of this ecosystem enhances growth and invasion of different pathogenic bacteria, further impairing the balance between the immune system and mucosal barrier. Moreover, altered microbiota due to H. pylori infection is involved in increasing the gastric T regulatory cells response in children. Since gastric homeostasis is defined by the partnership between commensal bacteria and host’s immune system, this review is focused on how pathogen recognition through toll-like receptors (TLRs—an essential class of pathogen recognition receptors—PRRs) on the surface of macrophages and dendritic cells impact the immune response in the setting of H. pylori infection. Further studies are required for delineate precise role of bacterial community features and of immune system components.

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Genetic Polymorphisms of CXCL8 (−251) Are Associated with the Susceptibility of Helicobacter pylori Infection Increased the Risk of Inflammation and Gastric Cancer in Thai Gastroduodenal Patients

Iranian Journal of Allergy Asthma and Immunology ◽

10.18502/ijaai.v18i4.1417 ◽

2019 ◽

Cited By ~ 1

Author(s):

Wongwarut Boonyanugomol ◽

Kamolchanok Rukseree ◽

Worrarat Kongkasame ◽

Prasit Palittapongarnpim ◽

Seung-Chul Baik ◽

...

Keyword(s):

Gene Expression ◽

Gastric Cancer ◽

Helicobacter Pylori ◽

Cancer Progression ◽

Chemokine Receptor ◽

Gene Polymorphisms ◽

Inflammatory Responses ◽

Increased Risk ◽

Cxc Chemokine ◽

H Pylori

CXC Chemokine Ligand 8 (CXCL8) plays an important role in gastric inflammation and in the progression of gastric cancer induced by Helicobacter pylori (H. pylori) infection. The association of CXCL8, CXC Chemokine Receptor 1 (CXCR1), and CXC Chemokine Receptor 2 (CXCR2) polymorphisms with H. pylori infection and gastric cancer progression needs to be investigated in a population within an enigma area consisting of multiple ethnicities, such as Thailand. To analyze the relative risk of H. pylori infection and gastric cancer among Thai gastroduodenal patients, gene polymorphisms in CXCL8 (promoter region -251) and in CXCR1 and CXCR2 (receptors for CXCL8) were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allele specific-PCR (AS-PCR). We also determined the presence of cytotoxin-associated gene A (cagA) in Thai patients with H. pylori infection. Correlation between the CXCL8 (-251) polymorphism and CXCL8 gene expression was evaluated by quantitative reverse transcriptase-PCR (qRT-PCR). We found a significant association between the T/A and A/A genotypes of CXCL8 (-251) with H. pylori infection. However, no significant correlation was found between the CXCR1 (+2607) and CXCR2 (+1208) gene polymorphisms with H. pylori infection among Thai gastroduodenal subjects. Within the H. pylori-infected group of Thai gastroduodenal patients, no significant differences in cagA were observed. In addition, the A/A genotype of CXCL8 (-251) significantly correlated with the risk of gastric cancer and correlated with higher CXCL8 gene expression levels in Thai gastroduodenal patients. These results suggest that CXCL8 (-251) polymorphisms are associated with H. pylori infection, an increased risk of stronger inflammatory responses, and gastric cancer in Thai gastroduodenal patients.

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Immunoglobulin G Antibody against Helicobacter pylori: Clinical Implications of Levels Found in Serum

Clinical and Vaccine Immunology ◽

10.1128/cdli.9.5.1044-1048.2002 ◽

2002 ◽

Vol 9 (5) ◽

pp. 1044-1048 ◽

Cited By ~ 2

Author(s):

Tseng-Shing Chen ◽

Fen-Yau Li ◽

Full-Young Chang ◽

Shou-Dong Lee

Keyword(s):

Helicobacter Pylori ◽

Chronic Gastritis ◽

Predictive Value ◽

Linear Regression Analysis ◽

Serum Antibody ◽

Quantitative Detection ◽

Enzyme Linked Immunosorbent Assay ◽

Multivariate Linear Regression Analysis ◽

H Pylori ◽

Antibody Levels

ABSTRACT The clinical significance of high levels of antibody against Helicobacter pylori is still unclear. We sought to evaluate whether the serum antibody levels could predict the presence of macroscopic gastroduodenal disease, to identify factors that correlate with antibody levels in a multivariate context, and to determine the predictive value of antibody levels for diagnosing H. pylori infection. The grades of gastritis and density of H. pylori colonization were scored separately using the updated Sydney system for antral and body mucosa. An enzyme-linked immunosorbent assay (ELISA) for the quantitative detection in serum of IgG antibodies to H. pylori was performed. Of the 170 dyspeptic patients, 105 (62%) had H. pylori infection. There was no difference in antibody levels among endoscopic findings of normal mucosa, chronic gastritis, and duodenal ulcer. On multivariate linear regression analysis, the status of H. pylori infection, mononuclear cell infiltration of body mucosa, and age correlated with antibody levels. The negative predictive value for antibody levels of <30 U/ml is 94%, and the positive predictive value of antibody levels of >70 U/ml is 98%. We conclude that serum antibody levels do not predict the severity of gastroduodenal diseases or the density of H. pylori colonization in H. pylori-infected dyspeptic patients. Higher levels are associated with the presence of H. pylori infection, the chronic gastritis score of the corpus, and older age. Setting a gray zone is necessary for ELISA, since the accuracy in this zone does not allow a precise determination of H. pylori status.

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Chlamydia pneumoniae is a risk factor for coronary heart disease in symptom-free elderly men, but Helicobacter pylori and cytomegalovirus are not

Epidemiology and Infection ◽

10.1017/s0950268897008303 ◽

1998 ◽

Vol 120 (1) ◽

pp. 93-99 ◽

Cited By ~ 88

Author(s):

J. M. OSSEWAARDE ◽

E. J. M. FESKENS ◽

A. DE VRIES ◽

C. E. VALLINGA ◽

D. KROMHOUT

Keyword(s):

Coronary Heart Disease ◽

Helicobacter Pylori ◽

Heart Disease ◽

Coronary Heart Disease Risk ◽

Chlamydia Pneumoniae ◽

Disease Risk ◽

Coronary Event ◽

Elderly Men ◽

H Pylori ◽

Heart Disease Risk

To test the hypothesis that chronic infection with Chlamydia pneumoniae, Helicobacter pylori or cytomegalovirus is associated with coronary heart disease risk in elderly men, a nested case-control study in a cohort investigated in 1985 and 1990 in the town of Zutphen, The Netherlands, was designed. Fifty-four cases with a first diagnosed coronary event between 1985 and 1990, and 108 age-matched control subjects free of coronary heart disease during follow up were included in the study. The overall prevalence of antibodies to cytomegalovirus was 74·7%, to H. pylori 75·9% and to C. pneumoniae 84·0%. A high level of antibodies to C. pneumoniae was associated with an increased coronary heart disease risk (OR=2·76; 95% CI=1·31–5·81). This association was stronger in cases developing both myocardial infarction and angina pectoris, than in cases developing only one of these. This association was independent of potential confounders. Antibodies to cytomegalovirus or H. pylori were not associated with coronary heart disease risk. These results support the hypothesis of a role of chronic C. pneumoniae infections in the immunopathogenesis of atherosclerosis.

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Serum Antibody Responses to Helicobacter pylori and the cagA Marker in Patients with Mucosa-Associated Lymphoid Tissue Lymphoma

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.6.4.633-638.1999 ◽

1999 ◽

Vol 6 (4) ◽

pp. 633-638 ◽

Cited By ~ 8

Author(s):

Anne Taupin ◽

Alessandra Occhialini ◽

Agnès Ruskone-Fourmestraux ◽

Jean-Charles Delchier ◽

Jean-Claude Rambaud ◽

...

Keyword(s):

Helicobacter Pylori ◽

Antibody Response ◽

Malt Lymphoma ◽

Lymphoid Tissue ◽

Serum Antibody ◽

Dot Blot ◽

Homologous Strain ◽

H Pylori ◽

Different Strains ◽

Dot Blot Analysis

ABSTRACT The lymphoma of the mucosa-associated lymphoid tissue (MALT) of the stomach has been linked to Helicobacter pylori infection, but the mechanisms involved in B-cell proliferation remain elusive. In a search for putative H. pylori-specific monoclonal immunoglobulin production, an H. pylori strain was isolated from 10 patients with MALT lymphoma and used to detect the specific serum antibody response to the homologous strain by immunoblotting. Moreover, the antigenicity of the different strains was compared by using each of the 10 sera. We found that the different strains induced highly variable patterns of systemic immunoglobulin G antibody response, although several bacterial antigens, such as the 60-kDa urease B, were often recognized by the different sera. ThecagA marker was detected in the strains by PCR with specific primers and by dot blot analysis, and the CagA protein was found in the sera of 4 of the 10 patients by immunoblotting. In conclusion, MALT lymphoma patients, like other patients with H. pylori gastritis, exhibit a polymorphic systemic antibody response, despite an apparently similar antigenic profile. The CagA marker of pathogenicity is not associated with this disease.

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Association of Helicobacter Pylori Infection with Cardiovascular Diseases Subjects from Cameroon, Using GastroPanel® Serological Biomarker Panel (Pepsinogen I; Pepsinogen II; Gastrin-17; Helicobacter Pylori IgG)

Journal of Advances in Microbiology ◽

10.9734/jamb/2021/v21i330332 ◽

2021 ◽

pp. 20-26

Author(s):

Alonge Ivo Ebule ◽

Valentine Ngum Ndze ◽

Ngouana Kammalac Thierry ◽

Guenou Etienne ◽

Chatchweng Kamtchweng Marie Felicite ◽

...

Keyword(s):

Helicobacter Pylori ◽

Cardiovascular Diseases ◽

Disease Risk ◽

Cardiovascular Complications ◽

Helicobacter Pylori Infection ◽

Central Hospital ◽

Pepsinogen I ◽

Informed Consent Form ◽

Artery Disease ◽

H Pylori

Introduction: Helicobacter pylori infection is associated with gastrointestinal diseases including atrophic gastritis and gastric cancer. Epidemiologic studies have demonstrated associations between H. pylori infection andextra gastrointestinal organ involvements including coronary artery disease and peripherical artery disease, dyslipidemia, insulin resistance and hematologic disorders. We sought to evaluate the prevalence of H. pylori infection in patients suffering cardiovascular diseases attending the Yaounde Central Hospital. Materials and Methods: Patients suffering from various cardiovascular complications were recruited at the Yaounde Central Hospital, between January and May 2019. The clinical and socio-demographic information of the patients was recorded. Five ml of blood were collected aseptically for Pepsinogen I and II enzymes, gastrin17 hormone and IgG anti H. pylori anti-body. The test parameters were analyzed using a GastroSoft software application. The data was analyzed using Epi Info 7.0. All statistics were 95% CI. Ethical clearance was also obtained from the National Ethics Committee. The study was accepted by the authorities of the Yaounde CentralHospital. All patients signed an informed consent form. Results: A total of 62 subjects were recruited aged 30-75 years, (mean±SD 52.03 ± 12,78 years); 34(54,84%) females aged 30 to 75years (mean±SD 54,47 ± 13,47 years) and 28 (45,16%) males aged 30 to 65,(mean±SD 49,07± 11,44years). Female/male ratio was 1:2. H. pylori seropisitivity occurred in 58 (93,55%) of the subjects (IgG ≥30 EIU). H. pylori seropositivity was significantly associated with high blood pressure (RR=2.2 95%C.I 1.67 -2.96, p=0, 024). Significantly low Triglyceride concentrations were observed in H. pyloripositive(0,51±0,03g/l) compared to negative subjects (1,04 ± 0,50g/l), (p=0.03). A significant inverse correlation was observed between IgG levels and blood glucose levels (r= 0,4 p=0, 004). Conclussion: The study indicates that H. pylori infection is highly associated with various cardiovascular complications and disease risk factors.

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Contribution of Secretory Antibodies to Intestinal Mucosal Immunity against Helicobacter pylori

Infection and Immunity ◽

10.1128/iai.01424-12 ◽

2013 ◽

Vol 81 (10) ◽

pp. 3880-3893 ◽

Cited By ~ 17

Author(s):

Rebecca J. Gorrell ◽

Odilia L. C. Wijburg ◽

John S. Pedersen ◽

Anna K. Walduck ◽

Terry Kwok ◽

...

Keyword(s):

Helicobacter Pylori ◽

Antibody Response ◽

Bacterial Load ◽

Secretory Iga ◽

Mouse Strains ◽

Wild Type ◽

Content Type ◽

Immunoglobulin Receptor ◽

H Pylori ◽

Secretory Antibodies

ABSTRACTThe natural immune response toHelicobacter pylorineither clears infection nor prevents reinfection. However, the ability of secretory antibodies to influence the course ofH. pyloriinfection has not been determined. We compared the natural progression ofH. pyloriinfection in wild-type C57BL/6 mice with that in mice lacking the polymeric immunoglobulin receptor (pIgR) that is essential for the secretion of polymeric antibody across mucosal surfaces.H. pyloriSS1-infected wild-type and pIgR knockout (KO) mice were sampled longitudinally for gastrointestinal bacterial load, antibody response, and histological changes. The gastric bacterial loads of wild-type and pIgR KO mice remained constant and comparable at up to 3 months postinfection (mpi) despite SS1-reactive secretory IgA in the intestinal contents of wild-type mice at that time. Conversely, abundant duodenal colonization of pIgR KO animals contrasted with the near-total eradication ofH. pylorifrom the intestine of wild-type animals by 3 mpi.H. pyloriwas cultured only from the duodenum of those animals in which colonization in the distal gastric antrum was of sufficient density for immunohistological detection. By 6 mpi, the gastric load ofH. pyloriin wild-type mice was significantly lower than in pIgR KO animals. While there was no corresponding difference between the two mouse strains in gastric pathology results at 6 mpi, reductions in gastric bacterial load correlated with increased gastric inflammation together with an intestinal secretory antibody response in wild-type mice. Together, these results suggest that naturally produced secretory antibodies can modulate the progress ofH. pyloriinfection, particularly in the duodenum.

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Helicobacter pylori Membrane Vesicles Stimulate Innate Pro- and Anti-Inflammatory Responses and Induce Apoptosis in Jurkat T Cells

Infection and Immunity ◽

10.1128/iai.01443-13 ◽

2014 ◽

Vol 82 (4) ◽

pp. 1372-1381 ◽

Cited By ~ 27

Author(s):

Jody Winter ◽

Darren Letley ◽

Joanne Rhead ◽

John Atherton ◽

Karen Robinson

Keyword(s):

Helicobacter Pylori ◽

T Cell ◽

Immune Cells ◽

Inflammatory Responses ◽

Membrane Vesicles ◽

Human Gastric Mucosa ◽

Content Type ◽

Toxin Content ◽

Anti Inflammatory ◽

H Pylori

ABSTRACTPersistentHelicobacter pyloriinfection induces chronic inflammation in the human gastric mucosa, which is associated with development of peptic ulceration, gastric atrophy, and gastric adenocarcinoma. It has been postulated that secretion of immunomodulatory molecules byH. pylorifacilitates bacterial persistence, and membrane vesicles (MV), which have the potential to cross the gastric epithelial barrier, may mediate delivery of these molecules to host immune cells. However, bacterial MV effects on human immune cells remain largely uncharacterized to date. In the present study, we investigated the immunomodulatory effects ofH. pyloriMV with and without the vacuolating cytotoxin, VacA, which inhibits human T cell activity. We show a high degree of variability in the toxin content of vesicles between twoH. pyloristrains (SS1 and 60190). Vesicles from the more toxigenic 60190 strain contain more VacA (s1i1 type) than vesicles from the SS1 strain (s2i2 VacA), but engineering the SS1 strain to produce s1i1 VacA did not increase the toxin content of its vesicles. Vesicles from all strains tested, including a 60190 isogenic mutant null for VacA, strongly induced interleukin-10 (IL-10) and IL-6 production by human peripheral blood mononuclear cells independently of the infection status of the donor. Finally, we show thatH. pyloriMV induce T cell apoptosis and that this is enhanced by, but not completely dependent on, the carriage of VacA. Together, these findings suggest a role forH. pyloriMV in the stimulation of innate pro- and anti-inflammatory responses and in the suppression of T cell immunity.

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Dissecting the Helicobacter pylori-regulated transcriptome of B cells

Pathogens and Disease ◽

10.1093/femspd/ftaa049 ◽

2020 ◽

Vol 78 (7) ◽

Author(s):

Bianca E Chichirau ◽

Tamara Scheidt ◽

Sebastian Diechler ◽

Theresa Neuper ◽

Jutta Horejs-Hoeck ◽

...

Keyword(s):

Helicobacter Pylori ◽

Immune System ◽

B Cells ◽

Mhc Class Ii ◽

Molecular Mechanisms ◽

Inflammatory Responses ◽

Group I ◽

Cytotoxin Associated Gene A ◽

And Migration ◽

H Pylori

ABSTRACT Persistent infections with the bacterial group-I carcinogen Helicobacter pylori (H. pylori) have been associated with a broad range of gastric disorders, including gastritis, ulceration, gastric cancer or mucosa-associated lymphoid tissue (MALT) lymphoma. Pathogenesis of H. pylori requires a balance between immune tolerance and defense. Although H. pylori induces inflammatory responses, the immune system cannot eliminate the pathogen. The detailed molecular mechanisms of how H. pylori interferes with cells of the immune system, in particular infiltrated B cells, are not well investigated. Previously, it was shown that the bacterial effector and oncoprotein cytotoxin-associated gene A (CagA) is delivered into B cells followed by its tyrosine-phosphorylation. To investigate the functional consequences in B cells colonized by CagA-positive H. pylori, we analyzed the global transcriptome of H. pylori-infected Mec-1 cells by RNA sequencing. We found 889 differentially expressed genes (DEGs) and validated JUN, FOSL2, HSPA1B, SRC, CXCR3, TLR-4, TNF-α, CXCL8, CCL2, CCL4, MHC class I and MHC class II molecules by qPCR, western blot, flow cytometry and ELISA assays. The H. pylori-specific mRNA expression signature reveals a downregulation of inflammation- and migration-associated genes, whereas central signal transduction regulators of cell survival and death are upregulated.

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Novel Diagnostic Tests to DetectHelicobacter pyloriInfection: A Pediatric Perspective

Canadian Journal of Gastroenterology ◽

10.1155/1999/304679 ◽

1999 ◽

Vol 13 (7) ◽

pp. 585-589 ◽

Cited By ~ 3

Author(s):

John D Snyder ◽

Sander Veldhuyzen van Zanten

Keyword(s):

Helicobacter Pylori ◽

Antibody Response ◽

Whole Blood ◽

Diagnostic Tests ◽

Less Invasive ◽

H Pylori

Because of the widespread problem ofHelicobacter pyloriinfections, there is an increased need for rapid, reliable and inexpensive diagnostic tests. Five recently developed tests that offer potential advantages because they are less invasive or permit easier acquisition of samples than available tests are assessed. The tests assessed are whole blood, saliva and urine assays that measure systemic antibody response toH pylori, stool tests that measureH pyloriantigens and string tests that recoverH pyloriorganisms.

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