Local and Systemic Immune and Inflammatory Responses to Helicobacter pylori Strains

ABSTRACT Colonization with Helicobacter pylori eventuates in varied clinical outcomes, which relate to both bacterial and host factors. Here we examine the relationships between cagA status, serum and gastric juice antibody responses, and gastric inflammation in dyspeptic patients. Serum, gastric juice, and gastric biopsy specimens were obtained from 89 patients undergoing endoscopy. H. pylori colonization and cagA status were determined by histology, culture, and PCR methods, and acute inflammation and chronic inflammation in the gastric mucosa were scored by a single pathologist. Serum and gastric juice antibodies to H. pylori whole-cell and CagA antigens were determined by enzyme-linked immunosorbent assay. Relationships between variables were sequentially analyzed using univariate and multivariate statistical methods. Of the 89 subjects, 62 were colonized by H. pylori. By univariate analyses, levels of serum immunoglobulin G (IgG) and IgA and gastric juice IgA antibodies against whole-cell and CagA antigens each were significantly higher in the H. pylori-positive group than in the H. pylori-negative group (P < 0.001). H. pylori and CagA seropositivities were both significantly associated with enhanced inflammation in gastric antrum and body (P < 0.02). The presence of gastric juice antibodies to H. pylori antigens was associated with more severe gastric inflammation. However, in multivariate analyses, only the presence of serum antibodies against CagA and, to a lesser extent, whole-cell antigens remained significantly associated with acute and chronic inflammation in antrum and body (P < 0.05). Thus, serum antibody response to CagA correlates with severity of gastric inflammation. Furthermore, given the relationships demonstrated by multivariate analysis, determination of gastric juice antibodies may provide a better representation of serum, rather than secretory, immune response.

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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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Antibody to Heat Shock Protein Can Be Used for Early Serological Monitoring of Helicobacter pylori Eradication Treatment

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.7.4.574-577.2000 ◽

2000 ◽

Vol 7 (4) ◽

pp. 574-577 ◽

Cited By ~ 12

Author(s):

Naoko Yunoki ◽

Kenji Yokota ◽

Motowo Mizuno ◽

Yoshiro Kawahara ◽

Masayasu Adachi ◽

...

Keyword(s):

Helicobacter Pylori ◽

Heat Shock ◽

Antimicrobial Agents ◽

Eradication Therapy ◽

Enzyme Linked Immunosorbent Assay ◽

Peptic Ulcers ◽

Whole Cell ◽

Humoral Immune ◽

Whole Cell Lysate ◽

H Pylori

ABSTRACT Infection with Helicobacter pylori induces humoral immune responses against various antigens of the bacterium. Heat shock proteins (hsps) are immunodominant antigens in various diseases including H. pylori infection. In the present study, we measured the anti-hsp antibody titers in 42 patients with H. pylori-infected peptic ulcers during a bacterial eradication study. The patients were treated with a proton pump inhibitor and antimicrobial agents to eradicate the organism. Their sera were obtained at pretreatment and at 1 month and 6 months after the eradication therapy. The titers of immunoglobulin G antibodies to theH. pylori hsp, whole-cell lysate, and urease (30-kDa subunit) antigens in serum were measured by a capture enzyme-linked immunosorbent assay. The levels of H. pylori hsp60 antibodies in sera collected 1 month after treatment had declined significantly, even when changes in the titers of antibodies to whole-cell and urease antigens were not apparent. These results suggest that measurement of antibodies to H. pylorihsp60 in serum is useful for the early monitoring of the effectiveness of eradication therapy.

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Helicobacter Pylori Infection in Patients with Gastric Adenocarcinoma

Tumori Journal ◽

10.1177/030089169608200108 ◽

1996 ◽

Vol 82 (1) ◽

pp. 40-44

Author(s):

Chew-Wun Wu ◽

Tzee-Chung Wu ◽

Yun-Ray Chang ◽

Shyh-Haw Tsay ◽

Shih-Jiun Yin ◽

...

Keyword(s):

Helicobacter Pylori ◽

Gastric Adenocarcinoma ◽

Serum Antibody ◽

Multivariate Logistic Regression Analysis ◽

Enzyme Linked Immunosorbent Assay ◽

Serum Samples ◽

Clinicopathologic Parameters ◽

The Difference ◽

H Pylori ◽

Infiltrative Tumor

We examined the biologic tumor behavior in Helicobacter pylori-seropositive patients with gastric adenocarcinoma. A total of 214 consecutive patients with pathologically confirmed adenocarcinoma of the stomach who underwent gastric resection were studied. The stored serum samples were tested for serum antibody to H. pylori by using a highly sensitive and specific IgG enzyme-linked immunosorbent assay. The difference in H. pylori-seropositive and seronegative patients with gastric adenocarcinoma was evaluated in terms of various clinicopathologic parameters. A multivariate logistic regression analysis was used to adjust for potential confounding variables. Antibodies to H. pylori were detected in 65.9% of patients with gastric adenocarcinoma. H. pylori-seropositive patients were younger than seronegative patients and had infiltrative tumor according to Ming's criteria. When adjusted for age, infiltrative tumor come out stronger. These findings suggest that H. pylori infection may be related to infiltrative type gastric adenocarcinoma; further study is necessary.

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Detection of Anti-VacA Antibody Responses in Serum and Gastric Juice Samples Using Type s1/m1 and s2/m2 Helicobacter pylori VacA Antigens

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.6.4.489-493.1999 ◽

1999 ◽

Vol 6 (4) ◽

pp. 489-493 ◽

Cited By ~ 21

Author(s):

Guillermo I. Perez-Perez ◽

Richard M. Peek ◽

John C. Atherton ◽

Martin J. Blaser ◽

Timothy L. Cover

Keyword(s):

Helicobacter Pylori ◽

Gastric Juice ◽

Antibody Responses ◽

Enzyme Linked Immunosorbent Assay ◽

Serum Samples ◽

Ulcer Disease ◽

Serum Igg ◽

Increased Risk ◽

Antigenic Properties ◽

H Pylori

ABSTRACT Several different families of vacuolating toxin (vacA) alleles are present in Helicobacter pylori, and they encode products with differing functional activities. H. pyloristrains containing certain types of vacA alleles have been associated with an increased risk for peptic ulcer disease. In this study, we tested serum samples and gastric juice from 19 H. pylori-negative and 39 H. pylori-positive patients for enzyme-linked immunosorbent assay reactivity with two different types of VacA antigens (types s1/m1 and s2/m2), which were purified from H. pylori 60190 and 86-338, respectively. Both antigens were recognized better by serum immunoglobulin G (IgG) fromH. pylori-positive persons than by serum IgG from H. pylori-negative persons (P < 0.01). The s1/m1 VacA antigen was better recognized by sera from patients carryingvacA type s1/m1 strains than by sera from patients carryingvacA type s2/m2 or s1/m2 strains (P < 0.01). Conversely, the s2/m2 VacA antigen was better recognized by sera from patients carrying type s2/m2 or s1/m2 strains (P= 0.03). Serum IgG anti-VacA antibodies were present more frequently in patients carrying type s1/m1 strains than in other H. pylori-positive patients (P = 0.0002). In addition, the highest levels of IgA anti-VacA antibodies were detected in the gastric juice of patients carrying type s1/m1 strains. These data indicate that different VacA isoforms have distinct antigenic properties and that multiple forms of VacA elicit antibody responses inH. pylori-positive humans.

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Serodiagnosis and Bacterial Genome of Helicobacter pylori Infection

Toxins ◽

10.3390/toxins13070467 ◽

2021 ◽

Vol 13 (7) ◽

pp. 467

Author(s):

Aina Ichihara ◽

Hinako Ojima ◽

Kazuyoshi Gotoh ◽

Osamu Matsushita ◽

Susumu Take ◽

...

Keyword(s):

Helicobacter Pylori ◽

Antibody Titer ◽

Bacterial Genome ◽

Serum Antibody ◽

Gene Mutations ◽

Bacterial Genomes ◽

Western Blots ◽

A Genome ◽

Vaca Gene ◽

H Pylori

The infection caused by Helicobacter pylori is associated with several diseases, including gastric cancer. Several methods for the diagnosis of H. pylori infection exist, including endoscopy, the urea breath test, and the fecal antigen test, which is the serum antibody titer test that is often used since it is a simple and highly sensitive test. In this context, this study aims to find the association between different antibody reactivities and the organization of bacterial genomes. Next-generation sequences were performed to determine the genome sequences of four strains of antigens with different reactivity. The search was performed on the common genes, with the homology analysis conducted using a genome ring and dot plot analysis. The two antigens of the highly reactive strains showed a high gene homology, and Western blots for CagA and VacA also showed high expression levels of proteins. In the poorly responsive antigen strains, it was found that the inversion occurred around the vacA gene in the genome. The structure of bacterial genomes might contribute to the poor reactivity exhibited by the antibodies of patients. In the future, an accurate serodiagnosis could be performed by using a strain with few gene mutations of the antigen used for the antibody titer test of H. pylori.

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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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A Novel Line Immunoassay Based on Recombinant Virulence Factors Enables Highly Specific and Sensitive Serologic Diagnosis of Helicobacter pylori Infection

Clinical and Vaccine Immunology ◽

10.1128/cvi.00433-13 ◽

2013 ◽

Vol 20 (11) ◽

pp. 1703-1710 ◽

Cited By ~ 26

Author(s):

Luca Formichella ◽

Laura Romberg ◽

Christian Bolz ◽

Michael Vieth ◽

Michael Geppert ◽

...

Keyword(s):

Helicobacter Pylori ◽

Immune Responses ◽

Virulence Factors ◽

Gastrointestinal Disease ◽

Individual Risk ◽

Enzyme Linked Immunosorbent Assay ◽

Type I ◽

Serologic Test ◽

Content Type ◽

H Pylori

ABSTRACTHelicobacter pyloricolonizes half of the world's population, and infection can lead to ulcers, gastric cancer, and mucosa-associated lymphoid tissue (MALT) lymphoma. Serology is the only test applicable for large-scale, population-based screening, but current tests are hampered by a lack of sensitivity and/or specificity. Also, no serologic test allows the differentiation of type I and type II strains, which is important for predicting the clinical outcome.H. pylorivirulence factors have been associated with disease, but direct assessment of virulence factors requires invasive methods to obtain gastric biopsy specimens. Our work aimed at the development of a highly sensitive and specific, noninvasive serologic test to detect immune responses to importantH. pylorivirulence factors. This line immunoassay system (recomLine) is based on recombinant proteins. For this assay, six highly immunogenic virulence factors (CagA, VacA, GroEL, gGT, HcpC, and UreA) were expressed inEscherichia coli, purified, and immobilized to nitrocellulose membranes to detect serological immune responses in patient's sera. For the validation of the line assay, a cohort of 500 patients was screened, of which 290 (58.0%) wereH. pylorinegative and 210 (42.0%) were positive by histology. The assay showed sensitivity and specificity of 97.6% and 96.2%, respectively, compared to histology. In direct comparison to lysate blotting and enzyme-linked immunosorbent assay (ELISA), therecomLine assay had increased discriminatory power. For the assessment of individual risk for gastrointestinal disease, the test must be validated in a larger and defined patient cohort. Taking the data together, therecomLine assay provides a valuable tool for the diagnosis ofH. pyloriinfection.

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Influence of Helicobacter pylori Infection on the Small Intestinal Mucosa

ISRN Endoscopy ◽

10.5402/2013/408931 ◽

2013 ◽

Vol 2013 ◽

pp. 1-5

Author(s):

Mitsunori Maeda ◽

Masakazu Nakano ◽

Hideyuki Hiraishi

Keyword(s):

Helicobacter Pylori ◽

Negative Relationship ◽

Mucosal Injury ◽

Enzyme Linked Immunosorbent Assay ◽

Small Intestinal Mucosa ◽

Significant Negative Relationship ◽

Positive Rate ◽

Intestinal Mucosal Injury ◽

Small Intestinal ◽

H Pylori

Background/Aims. To investigate the role of Helicobacter pylori infection in the development of enteritis (small intestinal mucosal injury). Methodology. Between April 2007 and January 2013, 99 patients undergoing capsule endoscopy (CE) were tested for anti-H. pylori immunoglobulin G antibody (Hp-IgG) using an enzyme-linked immunosorbent assay (ELISA). None of the patients had been treated for H. pylori infection or diagnosed as having Crohn’s disease or any other clinically apparent small intestinal disorders prior to the CE. Results. The overall Hp-IgG-positive rate was 26.3%. The incidence of enteritis, as diagnosed by CE, tended to be lower in the Hp-IgG-positive patients (23.1%) than in the Hp-IgG-negative patients (38.4%) (). When patients receiving aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs), well-known causes of enteritis, were excluded, the incidence of enteritis in the Hp-IgG-positive patients (11.7%) was significantly lower than that in the Hp-IgG-negative patients (43.7%) (). A binomial logistic regression analysis revealed a significant negative relationship between Hp-IgG positivity and the presence of enteritis in patients receiving neither aspirin nor NSAIDs (). Conclusions. Our data indicated that H. pylori positivity was inversely associated with the prevalence of enteritis.

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Preliminary Serological Study of Helicobacter pylori Infection in Some University Students

Recent Advances in Biology and Medicine ◽

10.18639/rabm.2020.958557 ◽

2020 ◽

Vol 6 ◽

pp. 1

Author(s):

Abdullah A Mahrazi ◽

Mohammad A Khibrani ◽

Khatib S Ismail ◽

Emad Abada ◽

◽

...

Keyword(s):

Helicobacter Pylori ◽

University Students ◽

Large Scale ◽

Confirmatory Test ◽

Enzyme Linked Immunosorbent Assay ◽

Blood Collection ◽

Igg Antibodies ◽

Igm Antibodies ◽

H Pylori

Helicobacter pylori has been associated with peptic ulcer and gastric carcinoma. This study aimed to find the seroprevalence of H. pylori infection in some male students of Jazan University, Saudi Arabia. Twenty students were enrolled in the study (n = 20). Informed consent was obtained from the students. About 2 ml blood was collected intravenously in Improvacuter® evacuated blood collection tubes. The blood was allowed to clot at room temperature. The serum was collected and stored at –20°C for further use. The separated serum was used to detect IgG and IgM antibodies by Enzyme Linked Immunosorbent Assay (ELISA) against H. pylori for the in vitro diagnosis. A total of 11 (55.00%) students tested positive for IgG antibodies against H. pylori indicating previous infection. All the samples tested negative for IgM antibodies against H. pylori indicating no active infection. The seroprevalance of IgG antibodies against H. pylori was found to be very high in some male university students and is a cause of concern regarding their health. Obesity (p < 0.05; Value statistically significant), stress and bad eating habits, eating out, drinking carbonated beverages, and eating spicy food were some of the factors found to be associated with IgG seropositive students. The students were counseled and were instructed to undergo a confirmatory test and get medical intervention. Further large-scale studies need to be performed to plan action against this disease causing organism and to improve the health of students.

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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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