Prevalence and distribution of Helicobacter pylori cagA and vacA genotypes in the Moroccan population with gastric disease

Helicobacter pylori infection is the etiologic agent of various gastric pathologies. The severity of disease outcome has been attributed to some H. pylori genotypes, which varies geographically. In Morocco, there are no data regarding the pattern of H. pylori genotypes; therefore, this is the first prospective study conducted in our country to investigate the genotype profiles (vacA and cagA) of H. pylori in patients with gastric pain. Endoscopic biopsies were obtained in patients attending the gastroenterology department of the Hospital University Hassan II of Fez for gastric pain and were directly used for H. pylori detection and genotyping by polymerase chain reaction (PCR). The SPSS software program was used to study the genotype correlation to different clinical outcomes. A total of 429 patients were included in this study, with an infection rate of 69.9%. cagA was detected in 42.3% of cases. However, vacA genotyping reveal a large predominance of s2m2. Infection with multiple strains was detected in 10.8% of cases and incomplete vacA was observed in 31.5%. In Morocco, vacA s1m1 was significantly associated to peptic ulcer diseases, while s2m2 was associated to gastritis. Moroccan H. pylori vacA genotype profiles differ from the Latin American, European, and South African profiles, with more similarities to the North African profile. Because of the small number of cases with gastric cancer, no correlations with H. pylori have been studied, so, further studies will be required in order to highlight the effects of those genes on this disease.     

CagA antibodies in Japanese children with nodular gastritis or peptic ulcer disease

cagA(+) Helicobacter pylori strains have been linked to more severe gastric inflammation, peptic ulcer disease, and gastric cancer in adults, but there have been few studies of cagA in children. We examined the relationship between H. pylori cagA status and clinical status in Japanese children. Forty H. pylori-positive children were studied: 15 with nodular gastritis, 5 with gastric ulcers, and 20 with duodenal ulcers. H. pylori status was confirmed by biopsy-based tests and serum anti-H. pylori immunoglobulin G (IgG) antibody. As controls, 77 asymptomatic children with sera positive for anti-H. pylori IgG were enrolled. Levels of IgG antibodies to CagA in serum were measured by an antigen-specific enzyme-linked immunosorbent assay. In 16 patients with successful H. pylori eradication, posttreatment levels of CagA and H. pylori IgG antibodies also were studied. The CagA antibody seropositivities of asymptomatic controls (81.8%) and patients with nodular gastritis, gastric ulcers, and duodenal ulcers (80.0 to 95.0%) were not significantly different. Compared with pretreatment levels of CagA antibodies, posttreatment levels decreased progressively and significantly. We conclude that, as in Japanese adults, a high prevalence of cagA(+) H. pylori strains was found in Japanese children, and that there was no association with nodular gastritis or peptic ulcer disease. In the assessment of eradicative therapies, monitoring of serum anti-CagA antibodies does not appear to offer any direct benefit over monitoring of anti-H. pylori antibodies.     

Association between Helicobacter pylori virulence factors and gastroduodenal diseases in Okinawa, Japan

The incidence of gastric cancer in Okinawa is lowest in Japan. Some previous reports using small number of strains suggested that the high prevalence of Helicobacter pylori with Western-type cagA in Okinawa compared to other areas in Japan might contribute to the low incidence of gastric cancer. It has still not been confirmed why the prevalence of Western-type cagA strains is high in Okinawa. We examined the association between the virulence factors of H. pylori and gastroduodenal diseases in Okinawa. The genotypes of cagA and vacA of 337 H. pylori strains were determined by PCR and gene sequencing. The genealogy of these Western-type cagA strains in Okinawa was analyzed by multilocus sequence typing (MLST). Overall, 86.4% of the strains possessed cagA: 70.3% were East-Asian type and 16.0% were Western type. After adjustment by age and sex, the presence of East-Asian-type cagA/vacA s1m1 genotypes was significantly associated with gastric cancer compared to gastritis (odds ratio = 6.68, 95% confidence interval = 1.73 to 25.8). The structure of Western-type CagA in Okinawa was different from that of typical Western-type CagA found in Western countries. Intriguingly, MLST analysis revealed that the majority of Western-type cagA strains formed individual clusters but not hpEurope. Overall, low prevalence of gastric cancer in Okinawa may result from the high prevalence of non-East-Asian-type cagA strains. The origin of Western-type cagA strains in Okinawa may be different from those of Western countries.     

Correlation between IL-8 induction, cagA status and vacA genotypes in 153 French Helicobacter pylori isolates

The polymorphism of clinical presentations associated with Helicobacter pylori infection is potentially due to differences in the virulence of individual strains. H. pylori virulence has been associated with the ability to induce secretion of interleukin-8 (IL-8), the vacA genotypes, and the cagA status. The aim of this study was to determine the virulence profiles of 153 French H. pylori isolates on the basis of vacA genotypes, cagA status, and IL-8 induction ability. A total of 153 H. pylori isolates from patients with chronic gastritis (n = 74) or gastro-duodenal ulcers (n = 79) was examined for vacA genotypes and cagA status by polymerase chain reaction (PCR) and dot blot, and for their ability to induce IL-8 secretion by HEp-2 cells. The prevalence of vacA genotypes was: s1/m1 44.3%, s1/m2 24.9%, and s2/m2 23.5%. The cagA gene was present in 64% of the strains. IL-8 secretion was induced by 58.7% of the isolates. The presence of the cagA gene was significantly correlated with the s1/m1 vacA genotype and with the induction of IL-8. Thirty-four strains were atypical (cagA-positive/IL-8 noninducer or cagA-negative/IL-8 inducer). vacA genotypes, cagA status, and IL-8 induction ability are not correlated with the presence or absence of ulcer. The cagA status is not sufficient to predict the proinflammatory ability of H. pylori.     

Colonisation density and topographic localisation of Helicobacter pylori do not depend on the cagA status

AIMS: To explore the correlation between the cagA status of Helicobacter pylori and the density and topographic localisation of H pylori. METHODS: Gastric antral biopsy specimens were taken from 716 consecutive patients, including 293 H pylori positive patients (124 men, 169 women; mean age, 52.6 years; range, 12-87). A serum sample was taken for determination of IgG anti-CagA antibodies (sensitivity of 94.4% and specificity of 92.5%). The density of H pylori was assessed semiquantitatively (grades I-IV) in biopsy specimens stained with the modified Giemsa stain. Topographic localisation was classified as follows: score A, H pylori closely attached to the mucosa; score B, H pylori attached to the mucosa and in the mucus; and score C, H pylori solely in the mucus. RESULTS: CagA antibodies were present in 154 (52.5%) of the patients. There was no significant difference in colonisation density and cagA status: grade I, 23 (14%); grade II, 78 (50.6%); grade III, 42 (27.5%); and grade IV, 11 (7.2%) in the cagA(+) strains and 29 (21.2%), 57 (40.8%), 38 (27%), and 15 (11%), respectively, in the cagA(-) strains. There was no difference in topographic localisation between cagA(+) and cagA(-)H pylori. Mean anti-CagA titres were 0.84, 0.84, 0.89, and 0.73 in patients with grades I-IV bacterial density, respectively. CONCLUSION: Antibody titres do not correlate with H pylori density and there is no difference in density between cagA(+) and cagA(-)H pylori strains. In addition there is no difference in topographic localisation between cagA(+) and cagA(-) H pylori strains.     

Serological differentiation of Helicobacter pylori CagA(+) and CagA(-) infections

Many Helicobacterpylori strains causing gastroduodenal diseases have a cagA gene encoding CagA protein, a virulence factor of these bacteria. Anti-CagA antibodies produced by the majority of people infected with CagA(+) strains can indicate such an infection. In this study, the efficacy of three immunoenzymatic tests for detecting CagA(+) and CagA(-) infections were compared: immunoblot (Milenia ID Blot H. pylori IgG; MB) and ELISA conducted either with a recombinant immunodominant fragment of CagA (rCagA) or the full-length CagA molecule (flCagA). The 13C-urea breath test (13C-UBT) was used for establishing H. pylori status. The serum samples from 157 individuals were used for serodiagnosis. H. pylori CagA(+) infection was detected in H. pylori-infected individuals with similar frequencies by MB (64%) and flCagA-ELISA (60%) and a little less frequently by rCagA-ELISA (53%). There was a high coincidence between the negative results of these three tests for H. pylori-uninfected individuals with no anti-CagA IgG in the serum (96-100%). The results show that rCagA-ELISA and, especially, flCagA-ELISA are easy, inexpensive and useful noninvasive assays for the discrimination of CagA(+) and CagA(-) H. pylori infections in subjects examined by urea breath test.     

The efficacy of laboratory diagnosis of Helicobacter pylori infections in gastric biopsy specimens is related to bacterial density and vacA, cagA, and iceA genotypes

A total of 500 consecutive patients undergoing upper endoscopy were biopsied and tested for H. pylori infection by the Campylobacter-like organism (CLO) test, culture, histology, and PCR. Serum samples were tested by two different serological assays. Patients were considered H. pylori positive if at least two of the four biopsy specimen-based methods yielded positive results. PCR had the highest diagnostic sensitivity (99.4%), followed by histology (92.2%), culture (89.5%), and the CLO test (89.0%). The specificities of all methods were higher than 98%. Of the organisms from the 181 PCR-positive patients, the vacA (s and m regions), cagA, and iceA genotypes were determined by reverse hybridization (line probe assay) or an allele-specific PCR. Organisms that were detected by PCR but that remained undetected by the CLO test were significantly more often vacA s1 (P = 0.006), m1 (P = 0.028), and cagA positive (P = 0.029) than vacA s2, m2, and cagA negative, respectively. Organisms that were detected by PCR but that remained undetected by culture or histology more often contained iceA1 (P = 0. 034 and P = 0.029, respectively) than iceA2. Higher H. pylori density was associated with vacA s2 (P = 0.024), vacA m2 (P = 0.050), and cagA-negative (P = 0.035) genotypes. Also, the diagnostic results of the CLO test (P = 0.001) and culture (P = 0.031) but not those of the PCR (P = 0.130) were significantly associated with the H. pylori density. The rate of detection by the four biopsy specimen-based tests was lower for patients who used proton pump inhibitors, but this was independent of the H. pylori genotypes. These observations may be explained by different bacterial densities, as established by the distinct genotypes of H. pylori, and confirm that the biologies of strains with such genotypes are considerably different.     

Genotyping of Helicobacter pylori strains in formalin-fixed or Formaldehyde-sublimate-fixed paraffin-embedded gastric biopsy specimens.

Different genotypes of Helicobacter pylori can play a role in the development of atrophic gastritis, peptic ulcer disease, and gastric carcinomas. In this study the authors developed polymerase chain reaction assays for the detection and identification of vacA (s- and m-regions), cagA, and iceA genotypes of H. pylori in formalin-fixed or formaldehyde-sublimate-fixed paraffin-embedded gastric biopsy specimens. Polymerase chain reaction products were analyzed by reverse hybridization on a line-probe assay. Complete genotyping was achieved in 26 of 28 samples (93%), and multiple genotypes, indicating the presence of multiple strains, were detected in nine samples (32%). This genotyping method offers the possibility for long-term retrospective studies on H. pylori genotypes and gastric pathology in the same archival gastric tissue specimens.     

Comparison of genotyping Helicobacter pylori directly from biopsy specimens and genotyping from bacterial cultures

PCR for vacA and cagA genotypes of Helicobacter pylori using DNA isolated from infected gastric biopsy specimens was approximately equal to genotyping using bacterial DNA from cultures. Inconsistent results were associated with low H. pylori density in biopsies. A higher proportion of mixed infection was found when biopsies were used.     

Heterogeneity of cag genotypes in Helicobacter pylori isolates from human biopsy specimens

The Helicobacter pylori chromosomal cluster of genes known as the cytotoxin-associated gene (cag) island may have different compositions in infecting strains. In this study, we analyzed 150 single colonies obtained from gastric biopsy specimens from 10 patients infected with cagA-positive H. pylori strains and sweep isolates (isolates harvested with sweep in different points of the plate) from 6 patients infected with cagA-negative strains. Three loci in the cag island (cagA, cagE, and virB11) and the conserved gene glmM (ureC) were investigated by PCR. The levels of anti-H. pylori and anti-CagA antibodies in patient sera were also measured. For subjects infected with cagA-negative strains, all sweep isolates were also negative for cagE and virB11, suggesting the complete absence of the cag island. For subjects infected with cagA-positive strains, most of the isolates were positive for all three genes studied, whereas 24.7% of the isolates had a partial or total deletion of the cag island. cagA, cagE, and virB11 were, respectively, present in 87.3, 77.3, and 90% of the colonies. The deletion of virB11 was always associated with the deletion of cagA and/or cagE. H. pylori colonies with different cag genotypes were isolated within a single gastric biopsy specimen from 3 of the 10 patients and were further characterized by random amplified polymorphic DNA (RAPD) analysis and by sequencing of an arbitrarily selected gene segment. Although the colonies had different cag genotypes, their RAPD profiles were highly similar within each patient, and the nucleotide sequences of the selected gene segment were identical. All of the patients had detectable antibodies against H. pylori, and 9 of 10 had anti-CagA antibodies. In conclusion, we show that a single infecting H. pylori strain may include variable proportions of colony subtypes with different cag genotypes. The extension of our analysis to patients with well-characterized gastric diseases may provide significant information on the relationship between cag genotypes and clinical outcomes of H. pylori infections.     

Genetic characterisation of Helicobacter pylori isolates from an Argentinean adult population based on cag pathogenicity island right-end motifs, lspA–glmM polymorphism and iceA and vacA genotypes

Isolates of Helicobacter pylori from 88 patients were characterised by cagA status, cagA pathogenicity island (PAI) right-end motifs, iceA, vacA and lspA-glmM genotypes, primarily by PCR-based analysis, to investigate whether Argentinean isolates differed from those recovered in southern Europe or other Latin American countries. PCR-based analysis of vacA alleles was confirmed by reverse hybridisation in 56 cases, while sequence analysis was performed either when iceA and vacA genotypes could not be determined by PCR, or to investigate PCR and reverse hybridisation vacA genotyping discordance. Typing by lspA-glmM restriction fragment length polymorphism was performed with HhaI and AluI. The pattern of cag PAI right-end motifs and the prevalence of type Ia were similar to those in isolates from southern European countries, with cagA(+)/iceA1/vacA-s1 m1 being the commonest genotype. Reverse hybridisation identified a vacA-s1a/s1b recombinant allele, confirmed by sequencing analysis. Analysis of lspA-glmM genotypes identified at least 73 unrelated strains. Few mixed infections were identified, but in one case, isolates from a single biopsy exhibiting two vacA alleles were shown by lspA-glmM fingerprints to be two unrelated strains. No associated effect on ulcer disease risk was demonstrated by analysis of cagA, vacA and iceA status. Overall, the isolates of H. pylori from Argentina were similar to isolates from southern Europe or Latin American countries, and infections were associated mainly with single H. pylori strains.     

Genetic diversity in the Helicobacter pylori cag pathogenicity island and effect on expression of anti-CagA serum antibody in UK patients with dyspepsia

AIMS: To investigate variation within the cag pathogenicity island (PAI) of Helicobacter pylori isolated from patients with dyspepsia in mid-Essex, and to evaluate the effect on expression of anti-CagA antibody. METHODS: Sixty two isolates of H pylori cultured from gastric biopsies were screened by specific PCR assays for the presence of cagA and other gene markers (cagD and cagE, and virD4) in the cag PAI. An enzyme linked immunosorbent assay (ELISA) kit (Viva Diagnostica helicobacter p120) was used to test for anti-CagA IgG antibody in matching sera. Isolates were also genotyped by vacuolating cytotoxin polymerase chain reaction (PCR) analysis, and tested for absence of the complete cag PAI (empty site PCR assay). RESULTS: Forty one of the H pylori isolates had a cag PAI containing cagA. One strain had no cagA but other cag PAI loci were present, whereas the remaining 20 strains had no detectable cag PAI markers. Anti-CagA IgG antibody was detected in 34 sera by the ELISA assay, and when compared with the cag PAI genotype of the infecting strain, accuracy, sensitivity, and specificity were 92%, 87%, and 100%, respectively. The seven discrepant or borderline strains in the ELISA were all vacA s1 but differed in other genotypic markers. CONCLUSIONS: The cag PAI was widely distributed in H pylori from patients with dyspepsia in mid-Essex who had different gastric pathologies. Infection with a strain having an uninterrupted cag PAI was associated with the presence of anti-CagA antibody in most patients. Discrepant ELISA results, mostly for elderly patients with duodenal ulcers, were attributed to cagA associated variation, particularly to the presence of mixed cagA+/cagA- cell variants in the infecting strain population. Tests for anti-CagA serum antibody were unreliable for predicting severity of clinical disease associated with H pylori infection in this series of patients.     

Helicobacter pylori cagA and vacA cytotoxin genes in Changsha,China

Cytotoxin-associated protein (cagA) and the vacuolating cytotoxin (vacA) encoded by cagA and vacA genes are virulence determinants of Helicobacter pylori. In earlier studies among Chinese patients, all H. pylori strains were cagA-positive and vacAs1a/m2 type. Here, we determine the cagA, vacA and allele status of H. pylori strains isolated from patients with upper gastrointestinal symptoms in Changsha, China. Forty strains of H. pylori isolated from patients with peptic ulcer disease between March 1997 and August 1999 were recovered from storage at -80 degrees C and studied by the polymerase chain reaction (PCR) for cagA and vacA genotypes. cagA was positive in 75% of H. pylori isolates. Patients with peptic ulcer demonstrated cagA in 83% (15/18), compared with 68% (15/22) patients with superficial gastritis. vacAs1 allele was carried in 82.5% (33/40) isolates, of which 52.5% (21/40) were subtype vacAs1a/m2 and 17.5% (7/40) were subtype vacAs1b/m2.     

Distinct diversity of vacA, cagA, and cagE genes of Helicobacter pylori associated with peptic ulcer in Japan

Colonization of the stomach mucosa by Helicobacter pylori is a major cause of acute and chronic gastric pathologies in humans. Several H. pylori virulence genes that may play a role in its pathogenicity have been identified. The most important determinants are vacA and cagA in the cag pathogenicity island (cagPAI) genes. In the present study, to consider the association of molecular genetics between vacA and the cagPAI regarding clinical outcome, we selected H. pylori strains with various genotypes of vacA in Japan and sequenced full-length vacA, cagA, and cagE genes. Sequencing of vacA and cagA genes revealed variable size, whereas the cagE gene was well conserved among strains. Each of the phylogenetic trees based on the deduced amino acid sequences of VacA, CagA, and CagE indicated that all three proteins were divided into two major groups, a Western group and an East Asian group, and the distributions of isolates exhibited similar patterns among the three proteins. The strains with s2 and s1a/m1a vacA genotypes and the Western-type 3' region cagA genotype were classified into the Western group, and the strains with the s1c/m1b vacA genotype and the East Asian-type 3' cagA genotype were included in the East Asian group. In addition, the prevalence of infection with the Western group strain was significantly higher in patients with peptic ulcer (90.0%, 9/10) than in patients with chronic gastritis (22.7%, 5/22) (chi2 = 12.64, P = 0.00057). These data suggest that the molecular genetics of vacA and cagPAI are associated and that the Western group with vacA and cagPAI genes is associated with peptic ulcer disease.     

Helicobacter pylori genotypes may determine gastric histopathology

The outcome of Helicobacter pylori infection has been associated with specific virulence-associated bacterial genotypes. The present study aimed to investigate the gastric histopathology in Portuguese and Colombian patients infected with H. pylori and to assess its relationship with bacterial virulence-associated vacA, cagA, and iceA genotypes. A total of 370 patients from Portugal (n = 192) and Colombia (n = 178) were studied. Corpus and antrum biopsy specimens were collected from each individual. Histopathological features were recorded and graded according to the updated Sydney system. H. pylori vacA, cagA, and iceA genes were directly genotyped in the gastric biopsy specimens by polymerase chain reaction and reverse hybridization. Despite the significant differences between the Portuguese and Colombian patient groups, highly similar results were observed with respect to the relation between H. pylori genotypes and histopathology. H. pylori vacA s1, vacA m1, cagA+ genotypes were significantly associated with a higher H. pylori density, higher degrees of lymphocytic and neutrophilic infiltrates, atrophy, the type of intestinal metaplasia, and presence of epithelial damage. The iceA1 genotype was only associated with epithelial damage in Portuguese patients. These findings show that distinct H. pylori genotypes are strongly associated with histopathological findings in the stomach, confirming their relevance for the development of H. pylori-associated gastric pathology.     

Relationship between Helicobacter pylori virulence genes and clinical outcomes in Saudi patients

Helicobacter pylori has been strongly associated with gastritis, gastric and duodenal ulcers, and it is a risk factor for gastric cancer. Two major virulence factors of H. pylori have been described: the cytotoxin-associated gene product (cagA) and the vacuolating toxin (vacA). Since considerable geographic diversity in the prevalence of H. pylori virulence factors has been reported, the aim of this work was to determine if there is a significant correlation between different H. pylori virulence genes (cagA and vacA) in 68 patients, from Saudi Arabia, and gastric clinical outcomes. H. pylor was recognized in cultures of gastric biopsies. vacA and cagA genes were detected by polymerase chain reaction (PCR). The cagA gene was obtained with 42 isolates (61.8%). The vacA s- and m- region genotypes were determined in all strains studied. Three genotypes were found: s1/m1 (28%), s1/m2 (40%) and s2/m2 (26%). The s2/m1 genotype was not found in this study. The relation of the presence of cagA and the development of cases to gastritis and ulcer was statistically significant (P < 0.05). The study showed a significant correlation between the vacAs1/m2 genotype and gastritis cases, and a significant correlation between vacAs1/m1 genotype and peptic ulcer cases. The results of this study might be used for the identification of high-risk patients who are infected by vacAs1/m1 genotype of H. pylori strains. In conclusion, H. pylori strains of vacA type s1 and the combination of s1/m1 were associated with peptic ulceration and the presence of cagA gene.     

Relationship between Helicobacter pylori iceA, cagA, and vacA Status and Clinical Outcome: Studies in Four Different Countries

There is continuing interest in identifying Helicobacter pylori virulence factors that might predict the risk for symptomatic clinical outcomes. It has been proposed that iceA and cagA genes are such markers and can identify patients with peptic ulcers. We compared H. pylori isolates from four countries, looking at the cagA and vacA genotypes, iceA alleles, and presentation of the infection. We used PCR to examine iceA, vacA, and cagA status of 424 H. pylori isolates obtained from patients with different clinical presentations (peptic ulcer, gastric cancer, and atrophic gastritis). The H. pylori isolates examined included 107 strains from Bogota, Colombia, 70 from Houston, Tex., 135 from Seoul, Korea, and 112 from Kyoto, Japan. The predominant genotype differed among countries: the cagA-positive iceA1 vacA s1c-m1 genotype was predominant in Japan and Korea, the cagA-positive iceA2 vacA s1b-m1 genotype was predominant in the United States, and the cagA-positive iceA2 vacA s1a-m1 genotype was predominant in Colombia. There was no association between the iceA, vacA, or cagA status and clinical outcome in patients in the countries studied. iceA status shows considerable geographic differences, and neither iceA nor combinations of iceA, vacA, and cagA were helpful in predicting the clinical presentation of an H. pylori infection.     

Prevalence of Helicobacter pylori vacA,cagA and iceA genotypes in Nigerian patients with duodenal ulcer disease

Distinct virulence factors of Helicobacter pylori have been associated with clinical outcome of the infection; however, considerable variations have been reported from different geographic regions. Data on genotypes of African H. pylori isolates are sparse. The aim of this study was to determine the prevalence of specific genotypes of H. pylori in Nigerian patients with duodenal ulcer and non-ulcer dyspepsia. H. pylori was cultured from endoscopic biopsies obtained from 41 Nigerian patients (19 with duodenal ulcer, 22 with non-ulcer dyspepsia). The vacA alleles, cagA and iceA genotypes were determined by PCR. The vacA s1,m1 and s1,m2 genotypes were found in 26.3% and 22.7%, and in 73.7% and 72.7% of H. pylori isolates from patients with duodenal ulcer and non-ulcer dyspepsia, respectively. The iceA1 genotype was present in 94.7% and 86.4% of isolates from duodenal ulcer and non-ulcer dyspepsia patients, respectively. cagA+ infection was found predominantly (> 90%) in Nigerian H. pylori isolates irrespective of the clinical diagnosis. In conclusion, vacA s1,m2, iceA1 and cagA+ are common genotypes of H. pylori isolated from Nigerian patients. As in several other developing countries there seems to be no association between these genotypes and duodenal ulcer disease.     

Local and systemic immune and inflammatory responses to Helicobacter pylori strains

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 sero-positivities 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.     

Evaluation of clarithromycin resistance and cagA and vacA genotyping of Helicobacter pylori strains from the west of Ireland using line probe assays

The prevalence of clarithromycin resistance-associated mutations, the cytotoxin-associated gene (cagA), and the various vacuolating cytotoxin (vacA) genotypes was determined in 50 gastric biopsy specimens from Helicobacter pylori-infected patients, using line probe assays. The clarithromycin resistance-associated mutation A2143G was detected in H. pylori strains from 26% of the specimens, which suggested that the high rate of H. pylori treatment failure in Ireland may be partly attributable to the presence of these mutations. All strains examined carried the vacA s1 genotype, and 76% were cagA positive. Of these 50 specimens, 13 (26%) carried H. pylori strains with vacA midregion genotype m1, 29 (58%) carried strains that were m2, 1 (2%) was infected by a strain that was positive for both m1 and m2, and 7 (14%) carried strains that could not be typed.