Page 1042 - Clinical Immunology_ Principles and Practice ( PDFDrive )

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Immunological Diseases of the

Gastrointestinal Tract

Peter J. Mannon

The gastrointestinal (GI) tract contains the largest mass of pylori infection (up to 30%) occur in PA, with antigastric antibod-
immune cells of any organ in the body. To manage the continuous ies present in up to 65% of patients with H. pylori infection
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exposure to environmental and dietary antigens as well as (and none in noninfected patients with gastritis). In addition,
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pathogens, commensal microbes, and their metabolic products, gastric mucosal CD4 T cells can display cross-reactivity to H -
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the gut uses a number of strategies that support mucosal structural K -ATPase and H. pylori antigens. The actual identity of H.
integrity and immune regulation to maintain homeostasis. In pylori infection as the major causal link to PA has not been
spite of these defenses, the GI tract is susceptible to chronic established.
immune-mediated inflammation from pathogens, autoimmunity,
and immunodeficiency. This chapter discusses some of the most Helicobacter pylori Gastritis
frequent immunological diseases of the GI tract likely to be H. pylori infection of the gastric mucosa has been identified as the
encountered in the clinic, including autoimmune gastritis, chronic leading cause of peptic ulcer disease and is a WHO-designated
Helicobacter pylori gastritis, celiac disease, inflammatory bowel class I carcinogen for gastric carcinoma. Current data consistently
diseases (IBDs; Crohn disease, ulcerative colitis [UC], microscopic show that primary infection is largely acquired in childhood,
colitis, and eosinophilic esophagitis) and GI complications of at which stage in life poor sanitation enhances acquisition via
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primary immunodeficiency. The coverage focuses on the clinical fecal/gastrooral pathways. Although acute infection can cause
presentation, mechanisms of disease, and approaches to diagnosis abdominal pain and dyspepsia, there is typically no clinical
and treatment of these conditions. recognition of acute infection. Rather, the burden of H. pylori
results from chronic infection of the stomach; H. pylori is uniquely
GASTRITIS adapted to the acidic environment of the stomach through
its ability to metabolize urea to ammonia, which provides a
Gastritis is a histological term that describes stomach inflam- buffered microenvironment that allows prolonged asymptomatic
mation resulting from toxic exposures, infection, idiopathic colonization.
inflammation, and autoimmunity. Although symptoms tend to The ability of H. pylori to confer risk of peptic ulcer disease
be very nonspecific, the etiology and treatment of gastritis can in 15% of chronically infected persons has been linked to H.
be extremely specific, particularly for H. pylori infection, which pylori infection lowering the mucus pH adjacent to the gastric
has important implications for outcomes and natural history. epithelium and increasing the permeability of the mucus to
hydrogen ions. In addition to inhibition of bicarbonate secretion
Atrophic Gastritis/Pernicious Anemia by the epithelium, expression of cytotoxins (vacuolating cytotoxin,
The most classic autoimmune disease of the GI tract is atrophic VacA) and upmodulation of the mucosal inflammatory response
gastritis characterized by antiintrinsic factor and antiparietal cell by virulence factors, such as CagA, may contribute to pathogenesis.
autoantibodies and an association with autoimmune thyroiditis, The recognition of H. pylori as a causative agent in the vast
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vitiligo, and type I diabetes. Loss of acid-producing parietal cells majority of recurrent peptic ulcers and that its elimination could
leads to atrophic gastritis or “pernicious anemia (PA).” The age-old cure this disease led to the Nobel Prize in Medicine or Physiology
stereotype of the patient with atrophic gastritis/PA is an older to Marshall and Warren in 2005.
Caucasian woman with progressive effects of iron and vitamin The development of peptic ulcer disease and adenocarcinoma
B 12 deficiency. However, a female preponderance (approximately caused by chronic H. pylori infection correlates with the anatomi-
2 : 1) notwithstanding, 25% of cases are diagnosed below age 50 cal distribution of inflammation. When H. pylori chronic gastritis
years, and disease does occur in African and Asian ethnicities. affects the antrum predominantly, there is an association with
The detection of both antiintrinsic factor and antiparietal cell duodenal ulcers, increased serum gastrin levels and excess acid
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serum antibodies has 73% sensitivity and 100% specificity for PA. 2 production, and no gastric mucosal atrophy. However, when
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Murine models suggested that induced immunity to H -K - H. pylori affects the body and the antrum in a confluent or
ATPase (the parietal cell membrane protein that secretes H ions patchy manner, intestinal metaplasia develops, oxyntic mucosa
into the gastric lumen) may result in PA. Although potentially atrophies, and acid production decreases. This latter type of
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pathogenic H -K -ATPase–responsive CD4 T cells can be isolated H. pylori chronic gastritis is associated with gastric ulcerations
from the gastric mucosa of patients with PA, it remains unclear and increased risk for adenocarcinoma and mucosa-associated
how these cells arise, but observations implicate a role for H. lymphoreticular tissue (MALT) B-cell lymphoma. Although
pylori infection. Antral inflammation (up to 92%) and mucosal eradication of H. pylori can reverse the mucosal atrophy and
atrophy (up to 30%) together with histological evidence of H. restore acid production in this setting, mucosal restoration occurs
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