J. I. Wyatt

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.

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.

Mucosal humoral immune response to Helicobacter pylori in patients with duodenitis.

The humoral immune response toHelicobacter pylori infection in the duodenum has been investigated by short-termin vitro culture, ELISA, and immunoblotting techniques.H. pylori IgA secretion by duodenal bulb biopsies was significantly increased (P<0.001) in patients with duodenitis. The IgA response toH. pylori in patients with duodenitis was restricted to the first part of the duodenum; second part duodenal biopsies secreting significantly (P<0.001) less IgA during culturein vitro. H. pylori IgG antibody secretion by cultured biopsies was also significantly increased (P<0.01) in patients with duodenitis and those with gastricH. pylori infection but without duodenitis. Immunoblotting of duodenal bulb culture supernatants showed positive recognition by the mucosal IgA response ofH. pylori antigens in the region of 120, 90, 61, and 31–26 kDa in patients with duodenitis. Serologically, such patients showed little evidence of IgAH. pylori antibodies by immunoblotting. These results demonstrate that the inflammatory response in the duodenal mucosa of patients with duodenitis represents a specific highly localized humoral response toH. pylori.

Helicobacter pylori associated chronic gastritis and peptic ulceration in patients taking non-steroidal anti-inflammatory drugs

Helicobacter pylori is now recognized as a frequent cause of histological chronic gastritis, and this has radically changed our understanding of this common condition. In the light of these developments, the traditional view that non‐steroidal anti‐inflammatory drugs are one of the common ‘environmental’causes of chronic gastritis has been re‐examined.

Peptic Ulcer in the Elderly: Not a Helicobacter-Related Condition?

Recent studies show that most peptic ulceration in adults is associated with Helicobacter gastritis and/or the use of non-steroidal anti-inflammatory agents (NSAIDS) [2]. These factors damage the mucosa and impair its defence against acid/peptic attack. The aim of our study was to determine the frequency of these two risk factors for peptic ulceration in elderly patients (aged ≥ 70 years) in comparision with younger adults.

Cytokines and Mucosal Immune Responses to Helicobacter pylori

Cytokines are well recognised as being important regulators of inflammatory responses [1]. They are synthesised by several different cell types, and individual cytokines have multiple overlapping regulatory immune functions [1] as well as affecting physiological responses [2]. Cytokines are generally short acting and produced locally. The role of cytokines in regulating human intestinal mucosal responses has not been studied in detail, and the cytokine responses of the gastrointestinal mucosa to bacterial colonisation are unclear. Recent studies in animal models suggest that cytokine production at mucosal sites in response to bacterial or endotoxin administration is distinct from systemic events [3, 4]. A knowledge of cytokine production at mucosal sites is therefore important to our understanding of host-bacterial interactions and the immunopathology of chronic infections at mucosal surfaces.

Duodenal secretion of Campylobacter pylori-specific antibodies: relationship to gastroduodenal inflammation

Campylobacter pylori is a recently discovered microorganism found in the stomach of most patients suffering from chronic active gastritis. It is also found on gastric epithelium in the duodenum in the majority of those with duodenitis and also duodenal ulcer disease. Although gastric colonisation has been shown to produce a specific systemic and local humoral immune response, the results of duodenal infection are unknown. We have investigated the duodenal humoral immune response to C. pylori colonisation in 32 patients with dyspepsia. In vitro production of C. pylori -specific antibodies in cultured duodenal biopsies was assessed by ELISA. The duodenal secretion of C. pylori -specific IgG and IgA was elevated in patients with C. pylori gastritis, higher titres of IgA being secreted by the first part of the duodenum than the second. In the first part of the duodenum patients with duodenitis secreted significantly higher levels of C. pylori -specific IgA than patients with gastric colonisation but normal duodenal histology (p<0.05). This study suggests that the mucosal immune response to antral C. pylori colonisation is not confined solely to gastric tissue. The raised titres of duodenal C. pylori -specific IgA secreted by patients with active duodenitis suggest an enhanced local response to C.pylori which may have relevance to the pathogenesis of this condition.