Background

Atrophic gastritis is a histopathologic entity characterized by chronic

inflammation of the gastric mucosa with loss of the gastric glandular cells and
replacement by intestinal-type epithelium, pyloric-type glands, and fibrous
tissue. [1] Atrophy of the gastric mucosa is the endpoint of chronic processes,
such as chronic gastritis associated with Helicobacter pylori infection, other
unidentified environmental factors, and autoimmunity directed against gastric
glandular cells. [1] See the images below.

Atrophic gastritis. Helicobacter pylori–

associated chronic active gastritis (Genta stain, 20x). Multiple organisms
(brown) are observed adhering to gastric surface epithelial cells. A
mononuclear lymphoplasmacytic and polymorphonuclear cell infiltrate is
observed in the mucosa.
View Media Gallery
 Atrophic gastritis. Intestinal
metaplasia of the gastric mucosa (Genta stain, 20x). Intestinal-type epithelium
with numerous goblet cells (stained blue with the Alcian blue stain) replace the
gastric mucosa and represent gastric atrophy. Mild chronic inflammation is
observed in the lamina propria. This pattern of atrophy is observed both in
Helicobacter pylori–associated atrophic gastritis and autoimmune gastritis.
View Media Gallery
The 2 main causes of atrophic gastritis result in distinct topographic types of
gastritis, which can be distinguished histologically. H pylori–associated
atrophic gastritis is usually a multifocal process that involves both the antrum
and the oxyntic mucosa of the gastric corpus and fundus, whereas
autoimmune gastritis essentially is restricted to the gastric corpus and fundus.
Individuals with autoimmune gastritis [2] may develop pernicious anemia
because of extensive loss of parietal cell mass and anti-intrinsic factor
antibodies.
H pylori–associated atrophic gastritis is frequently asymptomatic, but
individuals with this disease are at increased risk of developing gastric
carcinoma, which may decrease following H pylori eradication. [3] Patients with
chronic atrophic gastritis develop low gastric acid output and
hypergastrinemia, which may lead to enterochromaffin-like (ECL) cell
hyperplasia and carcinoid tumors. [4]
For patient education resources, see the Digestive Disorders Center, as well
as Gastritis.
The infection is usually acquired during childhood and progresses over the lifespan of
the individual if left untreated. The host response to the presence of H pylori is
composed of a T-lymphocytic and B-lymphocytic response, followed by infiltration of the
lamina propria and gastric epithelium by polymorphonuclear leukocytes (PMNs) that
eventually phagocytize the bacteria.
Significant damage associated with the release of bacterial and inflammatory toxic
products is inflicted on the gastric epithelial cells, resulting in increasing cell loss or
gastric atrophy over time. Weck published a study supporting their hypothesis that the
association between H pylori and chronic atrophic gastritis was greatly underestimated
due to the clearance of the infection in advanced stages of the disease.  [5] These results
suggest that the association is much stronger than estimated by most epidemiologic
studies to date. Another study also reported that mannan-binding lectin allele (MBL2
codon 54 B) is associated with a higher risk of developing more severe gastric mucosal
atrophy in H pylori–infected Japanese patients. [6]
During the process of gastric mucosal atrophy, some glandular units develop an
intestinal-type epithelium, and intestinal metaplasia eventually occurs in multiple foci
throughout the gastric mucosa when atrophic gastritis is fully established. Other glands
are simply replaced by fibrous tissue, resulting in an expanded lamina propria.  [7] Loss of
gastric glands in the corpus, or corpus atrophy, reduces parietal cell numbers, which
results in significant functional changes with decreased levels of acid secretion and
increased gastric pH. [8] Hypochloridia or achloridia raises serum gastrin levels, thereby
increasing the risk for the development of neuroendocrine tumors.  [8] Studies have also
reported that moderate alcohol consumption may be associated with atrophic gastritis
by facilitating H pylori clearance. [9]
H pylori–associated chronic gastritis progresses with 2 main topographic patterns that
have different clinicopathologic consequences.
The first is antral predominant gastritis. Inflammation that is mostly limited to the antrum
characterizes antral predominant gastritis. Individuals with peptic ulcers usually develop
this pattern of gastritis, and it is the most frequently observed pattern in Western
countries.
The second is multifocal atrophic gastritis. Involvement of the corpus, fundus, and
gastric antrum with progressive development of gastric atrophy (ie, loss of gastric
glands) and partial replacement of gastric glands by intestinal-type epithelium (intestinal
metaplasia) characterize multifocal atrophic gastritis. Individuals who develop gastric
carcinoma and gastric ulcers usually have this pattern of gastritis. This pattern is
observed more often in developing countries and in Asia.
Autoimmune atrophic gastritis
The development of chronic atrophic gastritis limited to corpus-fundus mucosa and
marked diffuse atrophy of parietal and chief cells characterize autoimmune atrophic
gastritis, as shown in the following two images.
 Patterns of atrophic gastritis
associated with chronic Helicobacter pylori infection and autoimmune gastritis.
View Media Gallery

Atrophic gastritis. Intestinal

metaplasia of the gastric mucosa (Genta stain, 20x). Intestinal-type epithelium
with numerous goblet cells (stained blue with the Alcian blue stain) replace the
gastric mucosa and represent gastric atrophy. Mild chronic inflammation is
observed in the lamina propria. This pattern of atrophy is observed both in
Helicobacter pylori–associated atrophic gastritis and autoimmune gastritis.
View Media Gallery
Autoimmune gastritis is associated with serum antiparietal and anti-intrinsic factor
antibodies that cause intrinsic factor (IF) deficiency, which, in turn, causes decreased
availability of cobalamin (vitamin B-12) and, eventually, pernicious anemia in some
patients.
Palladino reported that methylenetetrahydrofolate reductase (MTHFR) polymorphisms
may be associated with B12 deficiency and autoimmune atrophic
gastritis. [10] Autoantibodies are directed against at least 3 antigens, including IF,
cytoplasmic (microsomal-canalicular), and plasma membrane antigens. Two types of IF
antibodies are detected (types I and II). Type I IF antibodies block the IF-cobalamin
binding site, thus preventing the uptake of vitamin B12. Cell-mediated immunity also
contributes to the disease. [11]
T-cell lymphocytes infiltrate the gastric mucosa and contribute to the epithelial cell
destruction and resulting gastric atrophy. Stummvoll reported that Th17 cells induced
the most destructive disease with cellular infiltrates composed primarily of eosinophils
accompanied by high levels of serum IgE.  [12] Polyclonal Treg also suppresses the
capacity of Th1 cells and moderately suppresses Th2 cells, but it can suppress Th17-
induced disease only at early time points.
The major effect of Treg was to inhibit the expansion of the effector T cells. However,
effector cells isolated from protected animals were not anergic and were fully competent
to proliferate and produce effector cytokines ex vivo.  [12] The strong inhibitory effect of
polyclonal Treg on the capacity of some types of differentiated effector cells to induce
disease provides an experimental basis for the clinical use of polyclonal Treg in the
treatment of autoimmune disease in humans.
The above findings led to an interesting study by Huter et al, who reported that antigen-
specific-induced Treg are potent suppressors of autoimmune gastritis induced by both
fully differentiated Th1 and Th17 effector cells. The investigators analyzed the
suppressive capacity of different types of Treg to suppress Th1- and Th17-mediated
autoimmune gastritis by comparing nTreg with polyclonal TGFbeta-induced WT Treg
(iTreg) or TGFbeta-induced antigen-specific TxA23 iTreg in cotransfer experiments with
Th1 or Th17 TxA23 effector T cells. [13] Th1-mediated disease was prevented by
cotransfer of nTreg and also antigen-specific iTreg, whereas WT iTreg did not show an
effect. However, Th17-mediated disease was only suppressed by antigen-specific iTreg.
Preactivation of nTreg in vitro before the transfer did not increase their suppressive
activity in Th17-mediated gastritis, supporting the investigators' hypothesis.  [