Alimentary TractH+,K+-ATPase (proton pump) is the target autoantigen of Th1-type cytotoxic T cells in autoimmune gastritis☆☆
Section snippets
Patients
Five women (mean age, 48; range, 33–56 years) from Tuscany with type A chronic AIG and 5 women (mean age, 51; range, 40–59 years) with Helicobacter pylori–induced uncomplicated type B chronic gastritis without atrophy (Hp-CG) provided their informed consent for this study, which was performed after the approval by the local Ethical Committee. All AIG patients had serum gastric PCA, as assessed by indirect immunofluorescence. These autoantibodies proved to be specific for gastric H+,K+-ATPase,
Reactivity to H+,K+-ATPase and cytokine profile of gastric T-cell clones
In vivo–activated T cells present in the lymphocytic infiltrates of the gastric antrum and corpus of 5 PCA-positive patients with chronic AIG without evidence of previous or actual infection with H. pylori were isolated and cloned. Likewise, control T-cell clones were generated from in vivo–activated T cells isolated from the gastric antrum and corpus of 5 PCA-negative, age- and sex-matched patients with uncomplicated Hp-CG. A total number of 175 CD4+ and 55 CD8+ clones were obtained from the
Discussion
We have investigated the pathogenic mechanisms of human AIG in this study. Data showed for the first time that T cells specific for H+,K+-ATPase of parietal cells are present in the gastric mucosa of patients with AIG. These autoreactive T cells were found to be Th1 effector cells with cytolytic potential through both perforins and Fas–Fas ligand interaction, and we propose that parietal cell loss in AIG proceeds through an autoimmune T-cell attack. In vivo–activated T cells present in the
References (45)
The association of atrophic gastritis with autoimmune thyroid disease
J Clin Endocrinol Metab
(1975)- et al.
A study of autoimmune gastritis in the postpartum period and at a 5-year follow-up
Gastroenterology
(1992) - et al.
Gastric parietal cell antigens of 60-90 kDa and 100-120 kDa associated with autoimmune gastritis and pernicious anaemia. Role of N-glycans in the structure and antigenicity of the 60-90 kDa component
J Biol Chem
(1989) - et al.
Neonatal injection of native proton pump induces autoimmune gastritis in mice
Gastroenterology
(1997) - et al.
Molecular targets in pernicious anemia
Immunol Today
(1991) - et al.
Analysis of mononuclear cell infiltrate and cytokine production in murine autoimmune gastritis
Gastroenterology
(1996) - et al.
Effect of free fatty acids and detergents on H,K-ATPase. The steady-state ATP phosphorylation level and the orientation of the enzyme in membrane preparations
Biochim Biophys Acta
(1991) Programmed cell death: apoptosis and oncogenesis
Cell
(1991)- et al.
Single cell analyses of cytokine production
Curr Opin Immunol
(1997) - et al.
The gastric H+,K+-ATPase is a major autoantigen in chronic Helicobacter pylori gastritis with body mucosa atrophy
Gastroenterology
(1998)
Bugs on trial: the case of Helicobacter pylori and autoimmunity
Immunol Today
The parietal cell autoantigens recognized in neonatal thymectomy-induced gastritis are the α and β subunits of the gastric proton pump
Gastroenterology
T helper cell differentiation in multiple sclerosis and autoimmunity
Immunol Today
Is pathogenic humoral autoimmunity a Th1 response? Lessons from (for) myasthenia gravis
Immunol Today
Autoimmune gastritis and pernicious anemia
An evaluation of gastric and thyroid autoimmunity in relation to haematologic disorders
Semin Hematol
Ultrastructural localisation of gastric parietal cell antigen with peroxidase-coupled antibody
Lab Invest
Gastric parietal cell autoantigen physical, chemical and biological properties
Clin Exp Immunol
Major parietal cell antigen in autoimmune gastritis with pernicious anaemia is the acid producing H,K adenosine triphosphatase of the stomach
J Clin Invest
Autoimmune gastritis: tolerance and autoimmunity to the gastric H/K-ATPase (proton pump)
Autoimmunity
Experimental autoimmune gastritis in the Rhesus monkey
Clin Exp Immunol
Gastric autoantibodies and cell-mediated immunity in pernicious anemia—a comparative study
Scand J Gastroenterol
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Supported in part by grants from the University of Florence, the Italian Ministry of University and Scientific Research (MURST), and the Associazione Italiana per la Ricerca sul Cancro; and by grants of the Federation of European Microbiological Societies (FEMS) and The Netherlands Organisation for Scientific Research (NWO) (to M.P.B.).
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