Autoimmune gastritis: historical antecedents, outstanding discoveries, and unresolved problems.
ABSTRACT The earliest recorded history of autoimmune gastritis can be traced to 1849 in London, when Thomas Addison described "a very remarkable form of anemia" later called pernicious (fatal) anemia (PA). This was followed by the recognition of a gastric mucosal defect suspected to have a nutritional basis, the discovery of the megaloblast that characterized the anemia, the insufficiency of a dietary extrinsic factor characterized as vitamin B12 (cobalamin), and a gastric-secreted intrinsic factor. Treatment with vitamin B12 proved curative. The link between PA and gastritis and atrophy was first confirmed histologically after immediate fixation of the stomach postmortem and later, in the 1940s, by peroral tube biopsy. The causes of gastritis remained enigmatic until the era of autoimmunity, when autoantibodies were detected first to gastric intrinsic factor and then to gastric parietal cells. Hints of a dichotomy in pathogenesis of gastritis were crystallized by the description in 1973 of Type A (Autoimmune) and Type B (later, Bacterial) gastritis. Clarification was enhanced by identification in Type A gastritis of the autoantigen of the parietal cell antibody, by the alpha and beta subunits of gastric H+/K+ ATPase, and by the highly informative experimental murine model of postneonatal thymectomy autoimmune gastritis, and in Type B of the causative role of gastric infection with Helicobacter pylori (H. pylori). A denouement will require a full understanding of (1) the origin and pathogenetic contribution of antibody to intrinsic factor; (2) the connection, if any, between H. pylori infection and Type A autoimmune gastritis; and (3) the genetic contributions to gastritis, whether due to autoimmunity or to H. pylori infection.
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ABSTRACT: Among Western populations, the declining incidence of Helicobacter pylori infection coincides with a growing clinical impact of autoimmune gastritis. To describe the histological phenotype of autoimmune gastritis, also to test the prognostic impact of OLGA staging in the autoimmune setting. A single-institutional series (spanning the years 2003-2011) of 562 consecutive patients (M:F ratio: 1:3.7; mean age = 57.6 ± 14.4 years) with serologically confirmed autoimmune gastritis underwent histology review and OLGA staging. Helicobacter pylori infection was ascertained histologically in 44/562 cases (7.8%). Forty six biopsy sets (8.2%) featured OLGA stages III-IV; they included all four cases of incidental epithelial neoplasia (three intraepithelial and one invasive; three of these four cases had concomitant H. pylori infection). There were 230 (40.9%) and 139 (24.7%) cases, respectively, of linear and micro-nodular enterochromaffin-like cell hyperplasia; 19 (3.4%) type I carcinoids were detected. The series included 116 patients who underwent repeated endoscopy/biopsy sampling (mean time elapsing between the two procedures = 54 months; range 24-108). Paired histology showed a significant (P = 0.009) trend towards a stage progression [the stage increased in 25/116 cases (22%); it remained unchanged in 87/116 cases (75%)]. In autoimmune gastritis, the cancer risk is restricted to high-risk gastritis stages (III-IV), and is associated mainly with concomitant H. pylori infection. OLGA staging consistently depicts the time-dependent organic progression of the autoimmune disease and provides key information for secondary gastric cancer prevention strategies.Alimentary Pharmacology & Therapeutics 04/2012; 35(12):1460-6. · 4.55 Impact Factor
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ABSTRACT: It is now widely accepted that Helicobacter pylori may play a role in several extra-gastric diseases. In particular, H. pylori infection seems to be implicated in various autoimmune diseases. Many recent studies have shown a healing or an improvement in different autoimmune disorders after H. pylori eradication therapy in infected patients. The exact mechanisms behind this relationship remain under discussion, but molecular mimicry is a consistent hypothesis. This subject is particularly relevant taking into consideration the high prevalence of H. pylori infection, the existence of inexpensive and noninvasive diagnostic methods, as the urea breath test or the stool antigen test, and the low cost and toxicity of eradication treatment. If this connection becomes confirmed, it can change the diagnostic and therapeutic approach of some autoimmune diseases.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 04/2012; · 2.24 Impact Factor
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ABSTRACT: To study the association between Helicobacter pylori (H. pylori) infection and autoimmune type atrophic gastritis. Twenty-three patients with different grades of atrophic gastritis were analysed using enzyme immunoassay-based serology, immunoblot-based serology, and histology to reveal a past or a present H. pylori infection. In addition, serum markers for gastric atrophy (pepsinogen I, pepsinogen I/II and gastrin) and autoimmunity [parietal cell antibodies (PCA), and intrinsic factor (IF), antibodies] were determined. Of the 14 patients with severe gastric atrophy, as demonstrated by histology and serum markers, and no evidence for an ongoing H. pylori infection, eight showed H. pylori antibodies by immunoblotting. All eight had elevated PCA and 4/8 also had IF antibodies. Of the six immunoblot-negative patients with severe corpus atrophy, PCA and IF antibodies were detected in four. Among the patients with low to moderate grade atrophic gastritis (all except one with an ongoing H. pylori infection), serum markers for gastric atrophy and autoimmunity were seldom detected. However, one H. pylori negative patient with mild atrophic gastritis had PCA and IF antibodies suggestive of a pre-atrophic autoimmune gastritis. Signs of H. pylori infection in autoimmune gastritis, and positive autoimmune serum markers in H. pylori gastritis suggest an etiological role for H. pylori in autoimmune gastritis.World Journal of Gastroenterology 01/2010; 16(1):83-8. · 2.55 Impact Factor