CagA Antibodies Research Articles

Association between Helicobacter pylori antibodies and otolaryngological diseases

ObjectiveObservational studies have shown that Helicobacter pylori is related to some otolaryngological diseases. However, it is unclear if H. pylori infection causally affects these diseases. To elucidate H. pylori role in 12 common otolaryngological diseases, we conducted two-sample Mendelian randomization analysis. MethodsSingle-nucleotide polymorphisms associated with 7 H. pylori antibodies (IgG, CagA, Catalase, GroEL, OMP, UREA and Vac A) served as instrumental variables. We primarily employed random-effects inverse variance weighting for causal estimation, supplemented by MR Egger, weighted median, simple mode, and weighted mode. Sensitivity analyses, including heterogeneity, pleiotropy, and leave-one-out tests, validated robustness. ResultsMR analysis using inverse variance weighting (random effects) revealed genetically predicted H. pylori CagA antibodies correlated with increased risk of nonsuppurative otitis media (OR = 1.0778, 95% CI 1.0114–1.1487, p-value = 0.021). No causal relationship was observed between H. pylori antibodies and other common otolaryngological diseases. Sensitivity analyses found no pleiotropy or heterogeneity, affirming result reliability. ConclusionThis study suggests that the levels of H. pylori CagA antibodies may contribute to the development of nonsuppurative otitis media. Further studies are needed in the future to elucidate the specific mechanism of H. pylori in this disease. Level of evidenceLevel III.

Detection of Helicobacter pylori strain types and analysis of risk factors among subjects from Hainan Province, China.

To explore the prevalence of type I and type II Helicobacter pylori infection and investigate risk factors in a population from Hainan Province in China. Data came from a large, cross-sectional study conducted from August 2022 to April 2023 involving five cities of Hainan. Subjects with confirmed 14C-urea breath test (UBT) and positive serological assay were included. All subjects had a gastroscopy. According to presence or absence of CagA/VacA proteins, subjects were classified as either type I (present) or type II strains (absent). Gastroscopic findings and several socio-demographic factors were examined for correlation with antibody serotyping. In total, 410 subjects were investigated for H. pylori strain types. The overall prevalence of the highly virulent, type I H. pylori strain was 79% (324/410) and type II strain was 21% (86/410). There was a strong association between type I strain and peptic ulcer disease. Of several sociodemographic factors investigated, only smoking and data over baseline (DOB) values showed significant differences between type 1 and type II strains. Logistic regression analysis showed a lower risk of type I H. pylori infection in smokers compared with non-smokers, and a higher risk of H. pylori type I infection in subjects with medium and high data over baseline (DOB) values compared with subjects who had low DOB values. Highly virulent, type I H. pylori infections predominate in Hainan and the co-positivity of CagA and VacA antibodies are related to type I H. pylori infection. We found that Type I H. pylori was closely associated with peptic ulcer disease and the DOB values were generally high.

No evident causal association between Helicobacter pylori infection and colorectal cancer: a bidirectional mendelian randomization study

Observational studies have reported a correlation between Helicobacter pylori infection and colorectal cancer (CRC); however, the underlying cause has remained unclear. This research was aimed at determining whether there is a correlation between H. pylori infection and CRC by measuring the prevalence of H. pylori CagA antibodies and VacA antibodies. Using data from many genome-wide association studies (GWAS), we conducted a Mendelian randomization (MR) study with two sample GWAS. Then, we used bidirectional MR to evaluate the association between H. pylori infection and CRC for identifying causation. The most common method of analysis was the inverse variance-weighted technique. In addition, we performed supplementary analyses using the weighted median technique and MR-Egger regression. Horizontal pleiotropic outliers were identified and corrected using the MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) method. Genetically predicted anti-H. pylori IgG seropositivity was not causally associated with CRC [odds ratio (OR): 1.12; 95% confidence interval (CI): 0.98–1.27, P = 0.08] and neither were H. pylori VacA antibody levels (OR = 0.96, 95% CI: 0.90–1.02, P = 0.25) or H. pylori CagA antibody levels (OR = 1.00, 95% CI: 0.93–1.07, P = 0.92). Furthermore, reverse MR analysis did not reveal evidence for a causal effect of CRC on H. pylori infection. The weighted median, the MR-Egger method, and MR-PRESSO yielded identical results. Using genetic data, MR analysis showed there was no evidence for a causal association between seroprevalence of H. pylori infection and CRC. The relationship between H. pylori infection and CRC requires further research.

Helicobacter pylori Seropositivity, ABO Blood Type, and Pancreatic Cancer Risk from 5 Prospective Cohorts.

Helicobacter pylori infection may be a risk factor for pancreatic cancer, particularly infection by strains without the cytotoxin-associated gene A (CagA) virulence factor. Non-O blood type is a known risk factor for pancreatic cancer, and H. pylori gastric colonization occurs largely from bacterial adhesins binding to blood group antigens on gastric mucosa. We included 485 pancreatic cancer cases and 1,122 matched controls from 5 U.S. prospective cohorts. Prediagnostic plasma samples were assessed for H. pylori and CagA antibody titers. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for pancreatic cancer. ABO blood type was assessed using genetic polymorphisms at the ABO gene locus or self-report. Compared to H. pylori seronegative participants, those who were seropositive did not demonstrate an increased risk for pancreatic cancer (OR 0.83, 95% CI 0.65-1.06). This lack of association was similar among CagA seropositive (OR 0.75, 95% CI 0.53-1.04) and seronegative (OR 0.89, 95% CI 0.65-1.20) participants. The association was also similar when stratified by time between blood collection and cancer diagnosis (P-interaction=0.80). Consistent with prior studies, non-O blood type was associated with increased pancreatic cancer risk, but this increase in risk was similar regardless of H. pylori seropositivity (P-interaction=0.51). In this nested case-control study, history of H. pylori infection as determined by H. pylori antibody serology was not associated with pancreatic cancer risk, regardless of CagA virulence factor status. The elevated risk associated with non-O blood type was consistent in those with or without H. pylori seropositivity.

Association between serum vitamin D levels and Helicobacter pylori cytotoxic-associated gene A seropositivity: a cross-sectional study in US adults from NHANES III

ObjectiveTo assess the association of serum vitamin D (VD) levels and Helicobacter pylori (H. pylori) cytotoxic-associated gene A (CagA) seropositivity, and further explore potential effect modifiers in this association.DesignCross-sectional study.SettingData...

New Rapid Helicobacter Pylori Blood Test Based on Dual Detection of FliD and CagA Antibodies for On-Site Testing

Helicobacter pylori is the most prevalent bacterial infection, affecting half of the world's population, with a high morbidity and mortality rate.1,2 Several invasive and noninvasive testing procedures are available, and their selective use serves the specific needs of diverse clinical scenarios. For gastric cancer prevention, mass screening is necessary and requires a noninvasive, rapid, accurate and cost-effective test. For this purpose H pylori serology currently seems to be the preferred noninvasive diagnostic method. Population-based testing and treatment for H pylori is cost effective in high-risk countries, but less effective in low- and medium-risk countries.3,4 Many serologic tests are available on the market, with inconsistent performance often being observed. Therefore, international guidelines recommend considering only serologic tests with high accuracy that have been validated in the respective local populations. To date, no rapid point-of-care test (POCT) has reached a sufficient degree of accuracy.

Association between Helicobacter pylori Infection and Graves’ Disease: A Meta-Analysis

Background: Helicobacter pylori (H. pylori) infection is proposed to be related with autoimmune diseases, such as Graves’ disease. This study aimed to assess the association between H. pylori infection and Graves’ disease.Method: A systematic literature review was conducted using Pubmed and Cochrane library. The quality of enrolled studies was assessed by the Critical Appraisal Skills Program Oxford. A fixed-effect model approach was used if there was no heterogeneity; otherwise, a random-effect model was used. Heterogeneity was assessed using I2. Publication bias was assessed by funnel plot. All data were analyzed using REVIEW MANAGER 5.3.Results: Six studies from Europe and Asia involving 983 patients were included. Overall H. pylori infection was significantly associated with Graves’ disease (OR = 2.7; 95% CI: 1.47-4.99; p 0.001). In subgroup analysis of 3 studies using non-serological diagnostic method, the prevalence rate of H. pylori infection was higher in Graves’ disease group (78.26% vs. 42.42%) with significant relationship (OR = 4.93; 95% CI: 3.16-7.69; p 0.00001; I2 = 0%). The Cytotoxin associated gene A (CagA) antibody prevalence was significantly higher in Graves’ disease group (46.57% vs. 20.29%; OR = 4.41; 95% CI: 2.65-7.33; p 0.00001; I2 = 56%). No publication bias was observed.Conclusion: Our study showed association between H. pylori infection and Graves’ disease. It might suggest the need of H. pylori examination in Graves’ disease patients and the impact of H. pylori eradication in the treatment of Graves’ disease.

Helicobacter pylori CagA seropositivity in adult Bangladeshi patients with peptic ulcer and erosion

Background: CagA IgG antibody in sera might indicate presence of virulent Helicobacter pylori in patients with peptic ulcer disease. Present study was performed to find out the prevalence of CagA IgG antibody in patients with peptic ulcer/erosion.
 Methods: Any case that had peptic ulcer/erosion, plus positive for rapid urease test (RUT) or H. pylori stool antigen (HpSAg) or serum anti-H. pylori IgG/IgA were included in the study and named as H. pylori positive case. H. pylori positive cases were tested for CagA IgG antibody. Anti-H. pylori IgG, IgA and CagA IgG antibodies were determined by enzyme-linked immunosorbent assay (ELISA) and stool antigen by rapid immunochromatographic test (ICT). Urease production in biopsy sample was detected by RUT.
 Results: Total 86 H. pylori positive patients were included in the study. Out of 86 patients, CagA IgG was positive in 34 (39.5%; 95% CI: 0.30,0.50) cases. CagA seropositivity rate in ulcer and erosion cases were 58.8% (95% CI: 0.36,0.78) and 34.8% (95% CI: 0.25,0.47) respectively. H. pylori stool antigen and IgA antibodies were positive in all (100%) CagA antibody positive ulcer cases while the rates were significantly less among the CagA antibody negative cases (42.8% and 28.6%; p<0.05). However, in CagA antibody positive erosion cases, the rates were not significantly different from CagA antibody negative cases.
 Conclusion: The study has demonstrated that the CagA positive strain is less prevalent in erosion than ulcer cases.
 Ibrahim Med. Coll. J. 2020; 14(1): 36-40

Prevalence of undiagnosed thyroid dysfunction in correlation with Helicobacter pylori infection: cross-talk between Hashimoto\u2019s thyroiditis and Helicobacter pylori

BackgroundWorldwide, the prevalence of thyroid dysfunction is increasing and it is one of the leading endocrine disorders. The objective of the present study was to assess the prevalence of undiagnosed thyroid dysfunction and its association with Helicobacter pylori (HP) infection and to clarify the association between HP and Hashimoto’s thyroiditis.Patients and methodsA cross-sectional study was conducted among 300 unrelated patients; 187 patients had normal thyroid function and 113 patients had thyroid dysfunction. The patients were stratified into one of the following five groups based on the reference of the normal thyroid function test; thyroid-stimulating hormone and free thyroxine were used as the screening tests to diagnose thyroid dysfunction. HP antigen in the stool and antibodies against cytotoxin-associated gene A (cag-A), anti-thyroid peroxidase (anti-TPO) antibodies, and anti-thyroglobulin (anti-TG) antibodies were measured.ResultsOur results show that the prevalence of thyroid dysfunction was found in 37.6% of the studied population. The most frequent dysfunction was subclinical hypothyroidism (44.4%), followed by overt hypothyroidism (20.6%). Interestingly, the prevalence was higher in association with HP infection diagnosed by HP antigen and cag-A antibodies. There was statistically significant positive correlation between HP antigen and anti-TPO as well as anti-TG. Regarding cag-A. There were statistically significant positive correlations between antibodies against cag-A and anti-TG as well as anti-TPO. Interestingly, stepwise linear regression analysis showed that serum thyroid-stimulating hormone levels were independently correlated with free thyroxine, HP.ConclusionThe higher prevalence of thyroid dysfunction as observed in the current study was associated with Hashimoto’s thyroiditis. Further future multicenter studies with a bigger sample size are needed to validate our findings.

Analysis of serum gastric function and Helicobacter pylori infection in patients with gastric hyperplastic polyps and gastric fundic gland polyps

Objective To analyze the serum gastric function and Helicobacter pylori (HP) infection in patients with gastric hyperplastic polyps and gastric fundic gland polyps. Methods From December 2017 to December 2018, 135 patients with gastric polyps and pathologically confirmed gastric hyperplastic polyps and gastric fundic gland polyps were enrolled in the hospital of Xuzhou Medical University.Among them, 68 patients with hyperplastic polyps, 67 cases of the gastric fundic gland polyps.Serum Hp antibodies (UreA, UreB, VacA, CagA antibodies) were qualitatively detected by immunoblotting.Eighty patients with chronic superficial gastritis were selected as the control group.Three groups of serum pepsinogen-I (PG-I), pepsinogen-Ⅱ (PG-Ⅱ), gastrin were detected by enzyme-linked immunosorbent assay (ELISA). Gastrin-17(G-17) and calculate PGⅠ and PGⅡ ratio(PGR). Results The levels of serum PGⅡ (13.13(8.15, 20.30) μg /L) and G17 (8.44(3.72, 27.17) pmol/L) in the gastric hyperplastic polyp group were higher than those in the control group (9.16(5.56, 15.14) μg/L and 1.83(0.87, 5.95) pmol/L) (P<0.05), and the PGR level was lower than the control group (P<0.05); serum PGI (120.12(86.72, 174.70) μg/L), PGII (11.92(7.27, 22.26) μg/L), G17 (5.68(1.79, 14.65) pmol/L) in the gastric fundic gland polyp group was higher than the control group ((101.32(79.17, 131.33) μg /L, 9.16(5.56, 15.14) μg /L, 1.83(0.87, 5.95) pmol/L)(P均<0.05)) (P<0.05); serum G17 (8.44(3.72, 27.17) pmol/L) level in gastric hyperplastic polyp group was higher than gastric fundus polyp group (5.68(1.79, 14.65) pmol/L) (P<0.05); Hp infection rate in gastric hyperplastic polyp group61.76%(42/68)was higher than that in the gastric fundic gland polyp group40.30%(27/67) (P<0.05), and type I Hp was the main one (P<0.05). The serum PGⅡ and G17 levels in the gastric hyperplastic polyp group were higher than those of Hp negative (all P<0.05). There were no significant differences in serum PGI, PGⅡ, G17, and PGR levels between the HP-positive and negative-positive patients in the gastric fundus polyp group.The serum PGI and PGR levels in the hypertrophic polyp group were higher than those in the HPⅡ type (all P<0.05). There was no significant difference in the levels of serum PGⅠ, PGⅡ, G17, and PGR between the gastric fundic gland polyps group and the type Ⅱ. Conclusion Serum PG and G17 levels in patients with gastric hypertrophic polyps and gastric fundic gland polyps are higher than those in patients with chronic superficial gastritis.Patients with gastric hyperplastic polyps have higher HP infection rate and abnormal gastric function than gastric fundic gland polyps. Key words: Gastric hyperplastic polyp; Gastric fundus polyp; Helicobacter pylori; pepsinogen; Gastrin

Helicobacter pylori infection, chronic atrophic gastritis and risk of stomach and esophagus cancer: Results from the prospective population-based ESTHER cohort study.

Helicobacter pylori (H. pylori) infection is considered as principal cause of gastric cancer. It is further associated with a reduced risk of esophageal adenocarcinomas. In a large prospective population-based cohort study including 9,949 subjects with average observation time of 13.8 years, we assessed the risk of invasive gastric and esophageal cancer according to H. pylori infection and presence of chronic atrophic gastritis (CAG). Incidence rates and hazard ratios (HR) derived by Cox proportional hazards models and adjusted for relevant confounders were derived by seroprevalence of H. pylori and cytotoxin-associated gene A (CagA) antibodies and presence of CAG based on serological markers at baseline, respectively. During follow-up, 30 cases of noncardia gastric cancer and 33 cases of esophageal cancer were observed. Infection by H. pylori without and with expression of CagA was associated with a 5.2-fold (95% confidence interval 1.00-27.1) and an 18.2-fold (4.3-77.4) increase of noncardia gastric cancer incidence. A 0.65-fold decreased risk of esophageal adenocarcinomas (HR 0.35, 0.12-0.97) was observed among H. pylori-infected individuals. In participants infected with CagA expressed H. pylori, the presence of mild/moderate and severe CAG was associated with a 6.4-fold (1.3-31.0) and an 11.8-fold (3.1-45.4) increase of gastric cancer incidence, respectively. The results of this prospective population-based cohort study may contribute relevant evidence to the ongoing research of H. pylori-related cancers. The results may furthermore enhance the empirical basis for risk stratification among H. pylori-infected people and for recommendations regarding H. pylori screening and treatment among older adults in a Western population.

Tailor-Made Detection of Individual Phosphorylated and Non-Phosphorylated EPIYA-Motifs of Helicobacter pylori Oncoprotein CagA.

The gastric pathogen and carcinogen Helicobacter pylori (H. pylori) encodes a type IV secretion system for translocation of the effector protein CagA into host cells. Injected CagA becomes tyrosine-phosphorylated at the five amino acid residue Glutamate-Proline- Isoleucine-Tyrosine-Alanine (EPIYA)-sequence motifs. These phosphorylated EPIYA-sites represent recognition motifs for binding of multiple host factors, which then manipulate signaling pathways to trigger gastric disease. Thus, efficient detection of single phosphorylated EPIYA-motifs in CagA is required. Detection of phospho-CagA is primarily performed using commercial pan-phosphotyrosine antibodies. However, those antibodies were originally generated to recognize many phosphotyrosines in various mammalian proteins and are not optimized for use in bacteria. To address this important limitation, we synthesized 11-mer phospho- and non-phospho-peptides from EPIYA-motifs A, B, and C, and produced three phospho-specific and three non-phospho-specific rabbit polyclonal CagA antibodies. These antibodies specifically recognized the corresponding phosphorylated and non-phosphorylated EPIYA-motifs, while the EPIYA-C antibodies also recognized the related East-Asian EPIYA-D motif. Otherwise, no cross-reactivity of the antibodies among EPIYAs was observed. Western blotting demonstrated that each EPIYA-motif can be predominantly phosphorylated during H. pylori infection. This represents the first complete set of phospho-specific antibodies for an effector protein in bacteria, providing useful tools to gather information for the categorization of CagA phosphorylation, cancer signaling, and gastric disease progression.

Synergistic effect of 2D material coated Pt nanoparticles with PEDOT polymer on electrode surface interface for a sensitive label free Helicobacter pylori CagA(Ag-Ab) immunosensing

Helicobacter pylori (H. pylori) immunosensor based on platinum nanoparticles/poly(3,4-ethylenedioxythiophene)/reduced graphene oxide (Ptnano/PEDOT/red-GOx) modified gold electrode (Au-ET) was stepwise fabricated for the detection of cytotoxin-associated gene A antibody (CagA antibody). H. pylori is a microaerophillic and a Gram-negative bacteria that causes gastric ulcer leading eventually to adenocarcinoma (gastric cancer) in the later stage. H. pylori colonizes inner lining of human stomach. The developed diagnostic sensing interface would allow H. pylori (stomach infection) detection in early stage and would be a great contribution in clinical laboratories. In order to fabricate the immunosensor, CagA antigen was immobilized over the Ptnano/PEDOT/red-GOx modified Au-ET. Afterwards, the modified electrode was used for immuno-sensing of H. pylori specific Cag A antibodies in serum. At lower voltage the modified Ptnano/PEDOT/red-GOx/Au-ET shows an amplified sensing at the interface that makes the sensor more sensitive and specific. CagA is a virulence factor produced by H. pylori was determined by sudden decrease in the current. The laboratory synthesized nano composites were characterised by Scanning Electron Microscopy (SEM) and Atomic force microscopy (AFM) studies. The sensor had excellent linear range of 0.1 ng/ml to 30 ng/ml by limiting the detection range up to 0.1 ng/ml. Moreover, the novel immunosensor formed had good accuracy, precision and reliability. The immunosensor also showed an excellent storage stability by retaining 60–70% of its initial activity until 60 days kept at 4 °C. Highly sensitive interface of CagA antigen@Ptnano/PEDOT/red-GOx/Au-ET shows a promising future for H. pylori detection in diagnosis of stomach ulcer and stomach cancer.

Epitope peptides of Helicobacter pylori CagA antibodies from sera by whole-peptide mapping.

Helicobacter pylori CagA has been found to be immuno-dominant protein and utilized for the diagnosis of the infection with cagA-positive strains. It is important to characterize the peptide epitopes capable of detecting serum anti-CagA antibodies to understand CagA immunogenicity. Sera from 171 Japanese patients were subjected for the epitope mapping study. Eighty seven peptides were designed from the CagA consensus sequence and were used for ELISA protocol to test the serum samples. The reacting anti-CagA IgG amounts to specific peptides were measured and compared. The study revealed a strong reactivity of two peptides (c7-NNTEPIYAQVNKKKAGQAT and c8-AGQATSPEEPIYAQVAKKV) in H. pylori-infected group. Interestingly, these two peptides contained the well-known EPIYA-A and EPIYA-B region, respectively, which are two out of three CagA phosphorylation domains. Tyrosine-phosphorylation of these peptides reduced their reactivity in most sera. Moreover, additional peptides' mapping and chimeric-peptides' experiments indicated that the amino acids (QV and KK) accommodated in right-side flanking regions of both EPIYA-motifs were essential for their strong reactivity, whereas the third EPIYA-motif containing peptide (c12-GRSASPEPIYATIDFDEA) with differing flanking amino acids was not reactive in most cases. Our results suggest that the amino acid sequences constituted in the two reactive peptides are the important immunogenic regions of CagA which would be useful to develop next-generation peptide-based diagnostic assays.

HLA-DRB1*03 And DRB1*15 Frequency In Helicobacter Pylori Superficial Gastritis

Background: Background: Helicobacter pylori is an important gastrointestinal bacteria related to the development of superficial atrophic gastritis, peptic ulcer and gastric cancer. Human leukocyte antigens (HLA) may play an important roles in host immune responses to H pylori antigens.&#x0D; Aim of the study: to investigate the association between HLA-DRB1 genotypes and superficial gastritis with H. pylori infection in an Iraqi patients.&#x0D; Patients and methods: Sixty patients with superficial gastritis and 100 individuals with apparently normal results after endoscopic examination were recruited from Al-Kindy Teaching Hospital - Gastrocolonoscope Unit between January 2014 and July 2016. All study patients and controls group underwent upper gastrointestinal endoscopic examinations. They were analyzed for CagA antibodies Immunoglobulin G (IgG) for H. pylori and HLA Class II genotyping (HLA-DRB1).&#x0D; Results: Patients with superficial gastritis with H pylori. The infection showed significant expression (P=0.0001) DRB1*03:01 genotypes and DRB1*15:01 (P= 0.004) as compared to control group.&#x0D; Conclusions: Genetic factor may play a role in gastritis. HLA-DRB1*03 and HLA-DRB1*15 may increased the susceptibility to superficial gastritis in H pylori infected patients.

Differences in Helicobacter pylori and CagA antibody changes after eradication between subjects developing and not developing gastric cancer.

We evaluated serological Helicobacter pylori and cytotoxin-associated gene A (CagA) antibodies and endoscopic atrophy after eradication to identify factors predicting post-eradication gastric cancer development. Thirty-five patients with successful eradiation were divided into the post-eradication gastric cancer (13 cases) and non-gastric cancer (22 cases) groups. Serum Helicobacter pylori and CagA antibody titers and endoscopic atrophy before and six years after eradication were examined. Median Helicobacter pylori antibody titers had decreased significantly from baseline at 0.5–2 years after eradication in both groups (gastric cancer group, from 39.0 to 11.0 U/ml, p = 0.011; non-gastric cancer group, from 29.6 to 4.97 U/ml, p<0.001), but were significantly higher in the gastric cancer than in the non-gastric cancer group (p = 0.029). Median serum CagA antibody titers had also decreased significantly at 0.5–2 years after eradication (gastric cancer group, from 6.35 to 3.23 U/ml, p = 0.028; non-gastric cancer group, from 9.88 to 1.21 U/ml, p = 0.0045). Serum CagA in each group showed no significance. Endoscopic atrophy improved significantly after eradication in the non-gastric cancer, but not the gastric cancer, group (p = 0.0007). In conclusion, changes in Helicobacter pylori and CagA antibody titers and endoscopic atrophy after eradication might be useful as predictive factors for post-eradication gastric cancer.

Sero-prevalence of Helicobacter pylori CagA immunoglobulin G antibody, serum pepsinogens and haemoglobin levels in adults

Associations observed of Helicobacter pylori infection with haemoglobin levels are inconsistent. We examined associations of H. pylori sero-prevalence and serum pepsinogens (PGs), as non-invasive markers of atrophic gastritis, with haemoglobin levels. A cross-sectional study was undertaken among 654 Jewish and 937 Arab residents of Jerusalem, aged 25–78 years, randomly selected from Israel’s national population registry in age-sex and population strata. Sera were tested for H. pylori IgG, cytotoxin–associated gene A (CagA) antigen IgG antibody and PGs levels. Multivariable models were fitted to account for confounders. Participants with atrophic gastritis (PGI < 30 μg/L or a PGI: PGII < 3.0) had lower haemoglobin levels than those without: beta-coefficient −0.34 (95% CI −0.59, −0.09); in men −0.27 (95% CI −0.67, 0.12), and in women −0.43 (95% CI −0.74, −0.12). Lower haemoglobin levels were noted in persons with CagA antibody than in those H. pylori sero-negative or H. pylori-CagA sero-negative: beta-coefficient −0.14 (95% CI −0.29, 0.01). Anaemia was more common among women and men with than without atrophic gastritis: adjusted OR 2.58 (95% CI 1.48, 4.48) and 1.52 (95% CI 0.59, 3.95), respectively. In conclusion, independent of known correlates, atrophic gastritis and apparently CagA sero-positivity, a marker of H. pylori virulent strains, are associated with lower haemoglobin levels.

COMPARATIVE ANALYSIS OF SERUM ANTIBODY RESPONSES TO H.PYLORI AND TO RECOMBINANT CAGA IN THE COHORT OF WORKING-AGE MOSCOW ADULTS

Introduction. Helicobacter pylori (Hр) is a helix-shaped bacterium adapted evolutionary to living in the mucoid of stomach. Considered usually as one of the factors in the development of gastritis, peptic ulcer and gastric cancer, but the opposite opinions were also discussed. The aim of this study was to assess levels of serum antibodies to Hp and recombinant CagA in the cohort of working-age Moscow adults. Methods. Commercial ELISA kits “IFA-Helicobacter IgG”© (ZAO EKOlab, Russia) and “HelicoBest-antibodies”© (ZAO Vector-Best, Russia) were applied for the estimation of serum antibodies to Hp and CagA, correspondingly, in the observed cohort (both gender adults, N=319). Results. 85 % of the human cohort (N=271) had positive rates of IgG-antibodies against complex Hp antigen, with lognormal distribution of IgG titers (median 1:688; Q1 - Q3 1:370 - 1:1223) and cut-off value equal to 1:100. 54 % of the human cohort (N=172) were seropositive to recombinant CagA, with the levels of total serum antibodies (IgM, IgA and IgG) from 23 to 129 elisa units (median 87,9; Q1 - Q3 56,7 - 102,5) and cut-off value equal to 18,5 EU. The distribtion of CagA antibody levels was sharply different from lognormal distribution of IgG titers to complex Hp antigen and had signs of bimodality with the main maximum shifted to the right. In the complete cohort under observation (N=319), the levels of serum antibodies to Hp and CagA were associated with a weak (R=0,217), but highly significant (p=0,00009) positive linkage; human persons, seropositive to both antigens, had no any association between the markers. Discussion. Possible reasons of differences in the shape of distributions of the studied markers are discussed. Taking into account the extraordinary genetic variability of natural Hp isolates, lognormal distribution of antibodies to complex Hp antigen can reflect combinatorial differences in the degree of proximity of Hp antigenic determinants between human persons under observation and the antigenic preparation. Bimodal distribution of antibody levels to individual protein CagA, possibly, reflect genetically determined differences in immunoreactivity inside the observed cohort.

Human Leukocyte Antigen HLA-DRB1 Determinants Susceptibility to Gastroesophageal Reflux Disease

Background: Gastro oesophageal reflux disease (GERD) is characterized by diverse symptoms. There is an evidence for a genetic component to Gastro oesophageal reflux disease as supported by familial aggregation of this disease. Aim of the study was to investigate whether certain human leucocyte antigen genes HLA-DRB1 are associated with (GERD).Methods: Patients and controls were prospectively recruited from GIT center at Al-Kindy Teaching Hospital (Baghdad-Iraq) between January 2014 and July 2016. Sixty Iraqi Arab Muslim patients with a history of heartburn and dyspepsia were compared with 100 Iraqi Arab Muslims controls. All study patients and control groups underwent upper gastrointestinal endoscopic examinations and their serums were analyzed for CagA antibodies Immunoglobulin G (IgG) for H. pylori. HLA-DRB1 genotyping were done to both groups.Results: A total of 60 patients with erosive gastritis; GERD (Grade II and III) were evaluated, together with 100 controls. There is a significant increase of H. pylori infection (p=0.0001) in GERD patients than control group. HLA-DRB1* 15: 01was significantly increased in GERD patients in comparison with control group and an increased frequency of HLADRB1*11: 01 in control group compared with patients group.Conclusions: There is an association between HLA-DRB1 *15: 01 in GERD patients with H pylori positive patients.J MEDICINE Jan 2018; 19 (1) : 3-9

Correlation between Helicobacter pylori infection and primary infertility

Objective To investigate whether Helicobacter pylori (H.pylori) infection correlated with primary infertility, whether H. pylori infection caused the abnormal elevation of pro-inflammatory cytokines in primary infertility women, and whether cytotoxin associated gene A (CagA) protein played a key role in it. Methods From September 2015 to August 2016, 213 patients with primary infertility (infertility group) and 97 healthy individuals (control group) were selected. According to the common etiologies, patients with primary infertility were divided into groups with single-factor infertility, multifactorial infertility and unexplained reason groups. Serum H. pylori IgG antibody and CagA antibody were examined by H. pylori antibody type test kits. The levels of interleukin (IL)-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, IL-18, IL-1β, granulocyte-macrophage-colony stimulating factor (GM-CSF), interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α) and IL-12p70 were tested by ProcartaPlex Immunoassays. Chi square test and independent sample t test were performed for statistical analysis and risk was assessed. Results The positive rate of serum H. pylori IgG antibody of patients with primary infertility was higher than that of healthy control group (74.0%, 37/50 vs 56.7%, 55/97), and the difference was statistically significant (odds ratio (OR)=2.173, 95% confidence interval (CI) 1.028 to 4.595, χ2=4.216, P=0.040). There was no statistically significant difference in the positive rate of CagA antibody between primary infertility group and healthy control group (71.7%, 91/127 vs 74.5%, 41/55, OR=0.863, 95%CI 0.421 to 1.772, P>0.05). The serum levels of IL-8, IL-18 and IFN-γ of H. pylori positive primary infertility patients were (35.14±12.16), (11.83±4.01) and (11.05±3.17) ng/L, respectively, which were all higher than those of H. pylori positive healthy control group ((21.44±12.35), (9.89±2.23) and (8.90±1.45) ng/L, respectively) and H. pylori negative primary infertility group ((11.45±8.63), (7.90±0.99) and (8.18±1.10) ng/L, respectively), and the differences were statistically significant (t=6.947, 3.366 and 4.811; 15.596, 8.900 and 8.068; all P<0.05). The levels of IL-8, IL-18 and IFN-γ of H. pylori positive unexplained reason primary infertility group were (39.97±11.52), (13.12±4.61) and (13.06±3.70) ng/L, respectively, which were all significantly higher than those of single-factor infertility group ((31.65±11.20), (11.12±3.46) and (10.14±2.41) ng/L, respectively) and multifactorial infertility group ((30.47±8.49), (11.13±3.79) and (10.07±2.50) ng/L, respectively); and the differences were statistically significant (t=4.217, 2.942 and 5.738; 5.138, 2.562 and 5.218; all P<0.05). In H. pylori positive primary infertility group, the levels of IL-8, IL-18 and IFN-γ of CagA positive patients were (40.42±13.80), (13.04±4.19) and (11.51±3.41) ng/L, respectively, which were all significantly higher than those of CagA negative patients ((23.49±11.57), (9.08±1.43) and (10.04±2.29) ng/L, respectively) and CagA positive individuals in healthy control group ((21.85±12.14), (10.20±2.29) and (9.31±2.38) ng/L, respectively); and the differences were statistically significant (t=6.507, 5.533 and 2.380; 7.417, 4.069 and 3.738; all P<0.05). Conclusion CagA positive H. pylori infection can increase the level of serum pro-inflammatory cytokines, which may be a risk factor of primary infertility. To patients with unexplained primary infertility, this may be the cause of infertility. Key words: Helicobacter pylori; Primary infertility; CagA; Cytokines