R V Heatley

Mucosal IgA recognition of Helicobacter pylori 120 kDa protein, peptic ulceration, and gastric pathology.

The gastric IgA response to Helicobacter pylori was examined in 100 dyspeptic patients by means of immunoblotting of supernatants from antral biopsy and gastric mononuclear cell cultures. 76 of 78 patients with chronic gastritis, 2 of 8 with reactive gastritis, and 1 of 14 subjects with normal mucosa showed positive responses. Of patients with chronic gastritis, 75%, 83%, 97% and 76%, respectively, showed responses to the 120 kDa, 90 kDa, 61 kDa, and 31 kDa proteins. None of the 19 patients with chronic gastritis who did not recognise the 120 kDa protein had peptic ulcers, whereas 25 of 57 with positive recognition had peptic ulcers (p less than 0.001). Mucosal recognition of the H pylori 120 kDa protein was also positively associated with the activity of gastritis (polymorph infiltration) (p less than 0.002) and with the extent of surface degeneration (p less than 0.01). These findings suggest that 120-kDa-positive strains of H pylori have pathogenic features associated with active gastritis and peptic ulceration. Infection with 120-kDa-negative strains may explain why peptic ulceration develops in only a proportion of subjects infected with H pylori.

Mucosal tumour necrosis factor alpha and interleukin-6 in patients with Helicobacter pylori associated gastritis.

The production of tumour necrosis factor alpha (TNF alpha) and interleukin-6 by human antral mucosa during short term culture in vitro has been measured by enzyme linked immunosorbent assay. TNF alpha and interleukin-6 concentrations in culture supernatants were significantly greater (p less than 0.001) in patients infected with Helicobacter pylori, all of whom had chronic gastritis, than in patients who were H pylori negative with histologically normal gastric mucosa. Among H pylori colonised patients, TNF alpha concentrations were significantly higher in those with active gastritis and neutrophil infiltration into the epithelium than in those with inactive gastritis. In contrast, interleukin-6 concentrations were raised in both active and inactive gastritis. This study shows that H pylori gastritis is associated with increased gastric mucosal production of TNF alpha and interleukin-6 and that the nature of the mucosal cytokine response varies with the immunohistology of the disease. Inflammatory cytokines generated locally within the gastric mucosa could be relevant to the gastric physiology of H pylori infection.

Acute Helicobacter pylori infection: clinical features, local and systemic immune response, gastric mucosal histology, and gastric juice ascorbic acid concentrations.

The symptomatology of a case of acute infection with Helicobacter pylori is described, together with the accompanying changes in gastric mucosal histology, local and systemic humoral immune response, and gastric ascorbic acid concentration. The patient was an endoscopist, previously negative for the carbon-14 urea breath test, who had a week of epigastric pain and then became asymptomatic. H pylori was detected by culture of antral biopsy specimens and was still present after 74 days. Five days after infection the histological findings showed acute neutrophilic gastritis; by day 74 changes of chronic gastritis were evident. The patient seroconverted by IgG enzyme linked immunosorbent assay by day 74, but a mucosal IgM and IgA response was evident as early as day 14. Infection was accompanied by a transient hypochlorhydria but a sustained fall in gastric juice ascorbic acid concentration.

Campylobacter pyloridis and acid induced gastric metaplasia in the pathogenesis of duodenitis.

Biopsy specimens of gastric and duodenal mucosa from 290 patients were examined histologically for metaplasia and Campylobacter pyloridis. Estimates of pH on samples of fasting gastric juice from 55 of the patients were performed, and mucosal biopsy specimens from 33 patients were also cultured for C pyloridis. Active duodenitis was seen in 34 duodenal biopsy specimens. Thirty (88%) of the patients with active duodenitis had both greater than 5% gastric metaplasia in the duodenal specimen and C pyloridis associated gastritis. These two factors coexisted in only 0.43% of patients with no duodenal inflammation. When C pyloridis were seen histologically in duodenal biopsy specimens they were confined to areas of gastric metaplasia and never occurred in the absence of a polymorph infiltrate. Of the 55 patients with measurements of gastric juice pH, gastric metaplasia was present in the duodenum in 20 of 42 with a pH of less than 2.5, and in 0 of 13 with a pH of greater than 2.5. These results suggest that acid induced gastric metaplasia in the duodenum and C pyloridis associated gastritis may be synergistic in the pathogenesis of duodenitis; the metaplastic gastric epithelium allows C pyloridis to colonise the duodenal mucosa, where it produces an acute inflammatory response.

Systemic and local antibody responses to gastric Campylobacter pyloridis in non-ulcer dyspepsia.

Antibody titres to Campylobacter pyloridis in serum and gastric juice were estimated by an enzyme linked immunosorbent assay (ELISA) to whole organisms obtained from bacterial culture in 39 patients with non-ulcer dyspepsia. Whereas 20 of the 21 patients with chronic gastritis had gastric C pyloridis, 17 patients with no C pyloridis had normal histology in the gastric antrum and body. Significantly raised serum IgG and IgA antibody titres to C pyloridis were found in colonised patients with gastritis. Patients with raised IgG antibody to C pyloridis were also shown to have significantly raised titres to other Campylobacter species, suggesting antigenic cross reactivity. Gastric juice antibodies were also studied and IgA titres to C pyloridis were detected in a proportion of patients with gastritis, together with low levels of IgM, but no IgG.

Screening dyspepsia by serology to Helicobacter pylori

Owing to limited endoscopy resources, various screening strategies for endoscopy have been proposed. Helicobacter pylori can be detected with high sensitivity and specificity by serology, and therefore we assessed the effects on diagnostic accuracy and endoscopic workload of a policy of screening clinic patients with dyspepsia before endoscopy by a strategy based on age, Helicobacter pylori serology, and use of non-steroidal anti-inflammatory drugs. 1153 patients were studied, of whom 842 were of known histological H pylori status (histology group) and 293 had serum assessed prospectively by in-house and commercial ELISAs for detection of IgG antibodies to H pylori. Overall, the screening strategy would have reduced endoscopy workload by 23.3% (95% confidence interval 20.9-25.8%) and would have had a sensitivity for detection of peptic ulcer of 97.4% (94.5-99.1%). No peptic ulcer or malignant disease was missed in the patients studied prospectively, but 6 of 192 peptic ulcers in the histology group would have been missed. A policy of screening young dyspeptic patients for H pylori by serology is more sensitive than symptom-based screening strategies, and may have an important role in reducing endoscopy workload.

Local immune response to gastric Campylobacter in non-ulcer dyspepsia.

Colonising Campylobacter pyloridis were identified histologically in gastric biopsy specimens from 89% of 83 patients with non-ulcer dyspepsia and chronic gastritis, but not in 58 dyspeptic patients with normal mucosa. The presence and population density of organisms was associated with the presence of intraepithelial neutrophils. In vivo coating of the organisms by host immunoglobulin was investigated by immunoperoxidase staining of IgA, IgG, and IgM in 54 biopsy specimens. IgA coated bacteria were seen in all cases of active gastritis, and in 60% of biopsy specimens without intraepithelial neutrophils. Coating with IgG or IgM, or both, was correlated with activity of gastritis and was rarely seen in the absence of a neutrophil infiltrate.

Gastric epithelium in the duodenum: its association with Helicobacter pylori and inflammation.

Duodenal biopsy specimens from 471 adults and 47 children were examined to determine the prevalence and distribution of gastric epithelium in the duodenal bulb in relation to age, gender, gastroduodenal inflammation, smoking, alcohol and consumption of nonsteroidal anti-inflammatory drugs (NSAID). Gastric metaplasia was present in the anterior wall duodenal biopsy specimen in 31%, was significantly less common in patients under 17 than in adults, and was more common in males than females. In sixty two adults who underwent multiple radial duodenal biopsy gastric metaplasia was randomly distributed around the duodenal circumference; sixty three per cent of the patients with gastric metaplasia found on multiple biopsy were detected by just the anterior biopsy. Gastric metaplasia was not obviously associated with alcohol, cigarette, or NSAID consumption. While the presence of gastric metaplasia was associated with adulthood, male sex, and low fasting gastric juice pH, its extent was associated with active duodenitis and Helicobacter-associated gastritis. On logistic regression, gastric metaplasia in the duodenum and gastric Helicobacter pylori were independent predictors of active duodenitis, but were not significantly associated with inactive duodenal inflammation. H pylori was observed in duodenal biopsy specimens from 32 patients, all with active duodenitis; bacteria were present only on foci of gastric metaplasia, and were more likely to be seen when the metaplasia was extensive. It is proposed that inflammatory injury to the duodenal mucosa by H pylori may stimulate the development of further gastric metaplasia, and that the area of duodenum susceptible to colonisation with H pylori may therefore increase progressively until mucosal integrity is compromised and ulceration supervenes.

Campylobacter pyloridis--a new factor in peptic ulcer disease?

Commentaire a propos de cette bacterie qui peut provoquer des infections chroniques dont on a trouve recemment le role pathogene possible dans les ulcerations gastro-duodenales

Clinical economics review: medical management of inflammatory bowel disease

Inflammatory bowel diseases, although they are uncommon and rarely fatal, typically present during the period of economically productive adult life. Patients may require extensive therapeutic intervention as a result of the chronic, relapsing nature of the diseases. Their medical management includes oral and topical 5‐amino salicylic acid derivatives and corticosteroids, as well as antibiotics and immunosuppressive therapies. Assessing the cost‐effectiveness of rival treatments requires valid, reliable global assessments of outcome which consider quality of life, as well as the usual clinical end‐points. Macro‐economic studies of the overall impact of inflammatory bowel disease on health care systems have so far been largely confined to North America, where the total annual US costs, both direct and indirect, incurred by the estimated 380 000–480 000 sufferers has been put at around US2bn. Drugs were estimated to account for only 10% of total costs, whereas surgery and hospitalization account for approximately half. Studies from Europe suggest that the proportion of patients with Crohn’s disease and ulcerative colitis who are capable of full time work is 75% and 90%, respectively. However, whilst only a minority of inflammatory bowel disease patients suffer chronic ill health and their life expectancy is normal, obtaining life assurance may be problematic, suggesting a misconception that inflammatory bowel disease frequently results in a major impact on an individual’s economic productivity.