The gastric H+,K+-ATPase is a major autoantigen in chronic Helicobacter pylori gastritis with body mucosa atrophy

doi:10.1016/S0016-5085(98)70200-8

Gastroenterology

Volume 115, Issue 2, August 1998, Pages 340-347

https://doi.org/10.1016/S0016-5085(98)70200-8 Get rights and content

Abstract

Background & Aims: A subgroup of Helicobacter pylori–infected patients develops autoantibodies to gastric parietal cell canaliculi. The aim of this study was to define the unknown autoantigen. Methods: We screened 72 H. pylori–infected patients, 5 patients with autoimmune gastritis, and 36 healthy controls for immunoglobulin G autoantibodies to canaliculi by immunohistochemistry. The antigen specificity was determined by immunoprecipitation of the murine gastric H⁺,K⁺-adenosine triphosphatase (H⁺,K⁺-ATPase) expressed in oocytes and by immunoblotting on human gastric membranes from the body mucosa. Results: Autoantibodies specific for the conformational peptides of the H⁺,K⁺-ATPase were detected in 3% (1/36) of controls, in all patients with autoimmune gastritis (5/5), in 25% (18/72) of H. pylori–infected patients, and in 47% (15/32) of the infected patients with anticanalicular autoantibodies. No other major autoantigen was identified. Atrophy in the gastric body mucosa was found in 60% (9/15) of infected patients with both anticanalicular and anti–H⁺,K⁺-ATPase antibodies, but only in 13% (5/37) of infected patients lacking both autoantibodies (P < 0.01). Conclusions: The gastric H⁺,K⁺-ATPase is a major autoantigen in H. pylori–associated antigastric autoimmunity. Thus, anti–H⁺,K⁺-ATPase autoantibodies, which are closely linked to classical autoimmune gastritis, are also significant indicators for body mucosa atrophy in chronic H. pylori gastritis.

GASTROENTEROLOGY 1998;115:340-347

Section snippets

Patients, biopsy specimens, and sera

One hundred thirteen consecutive patients (62 female, 51 male; mean age, 51.4 years; range, 21–87 years) who underwent diagnostic esophago-gastro-duodenal endoscopy for upper abdominal complaints in Erlangen, Germany (n = 74), and in Brescia, Italy (n = 39), were included in the study.

From all patients, four gastric biopsy specimens (two from the antrum and two from the body mucosa) were histologically examined by one experienced histopathologist (T.K.) in H&E stains. In particular, type,

Anticanalicular autoantibodies and gastric mucosa atrophy

Of the 113 patients included in this study, 72 were infected with H. pylori and had chronic active gastritis. Five other patients had autoimmune gastritis, 4 of them with pernicious anemia. No major histopathologic changes could be detected in the gastric mucosa of the other 36 patients (normal controls). All patients with classical autoimmune gastritis had severe atrophic body gastritis. Body atrophy was also found in 28% (20/72) of the patients with chronic H. pylori gastritis and was

Discussion

The H⁺,K⁺-ATPase is known to be the key autoantigen in autoimmune gastritis, and both the α and the β subunit of the proton pump are the major molecular targets recognized by antiparietal cell autoantibodies.16, 17, 18, 19, 20, 21 However, it is not known whether the presence of anti–H⁺,K⁺-ATPase or antiparietal cell serum autoantibodies is really specific for classical autoimmune gastritis defined by histopathology. Particularly, the finding of autoantibodies binding to the canaliculi of

Acknowledgements

The authors thank Dr. Jean-Pierre Kraehenbuhl (Institute of Biochemistry and ISREC, Epalinges) for helpful discussions; Dr. Bernard Rossier and Dr. Käthi Geering (Institute of Pharmacology and Toxicology, University Lausanne) for supplying the Xenopus oocyte system; Dr. Emanuela Felley-Bosco (Institute of Pharmacology and Toxicology, University Lausanne) for technical advice; and Martina Rembeck (Institute of Pathology, University Erlangen-Nürnberg) for excellent technical assistance.

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^☆: Address requests for reprints to: Gerhard Faller, M.D., Institute of Pathology, University of Erlangen-Nürnberg, Krankenhausstrasse 8-10, 91054 Erlangen, Germany. e-mail: [email protected]; fax: (49) 9131-854745.

^☆☆: Supported by grant 31-43240.95 from the Swiss National Science Foundation (to D.C.) and Interdisciplinary Center for Clinical Research at the University of Erlangen-Nürnberg, Germany.

^★: The first three authors contributed equally to this work.

^★★: Dr. Claeys' current address is: Central Laboratory of Clinical Chemistry, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.

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Alimentary TractThe gastric H+,K+-ATPase is a major autoantigen in chronic Helicobacter pylori gastritis with body mucosa atrophy☆,☆☆,★,★★

Abstract

Section snippets

Patients, biopsy specimens, and sera

Anticanalicular autoantibodies and gastric mucosa atrophy

Discussion

Acknowledgements

Gastroenterology

Gastroenterology

Gastroenterology

J Biol Chem

Trends Microbiol

Gastroenterology

J Biol Chem

Gastroenterology

Lancet

Helicobacter pylori infection in peptic ulcer disease

Scand J Gastroenterol

Helicobacter pylori and the risk and management of associated diseases: gastritis, ulcer disease, atrophic gastritis and gastric cancer

Aliment Pharmacol Ther

Antigastric autoantibodies in Helicobacter pylori gastritis: prevalence, in-situ binding sites and clues for clinical relevance

Virchows Arch

Antigastric autoantibodies in Helicobacter pylori infection: implications of histological and clinical parameters of gastritis

Gut

H,K-ATPase

Curr Opin Nephrol Hypertens

Apoptosis in chronic gastritis and its correlation with antigastric autoantibodies

Virchows Arch

Potential role of molecular mimicry between Helicobacter pylori lipopolysaccharide and host Lewis blood group antigens in autoimmunity

Infect Immun

Lipopolysaccharide of the Helicobacter pylori type strain NCTC 11637 (ATCC 43504): structure of the O antigen chain and core oligosaccharide regions

Biochemistry

Alimentary Tract
The gastric H⁺,K⁺-ATPase is a major autoantigen in chronic Helicobacter pylori gastritis with body mucosa atrophy☆,☆☆,★,★★