Helicobacter pylori, iron deficiency, and gastric autoimmunity

We read with interest the article by Hershko et al,¹  which reported that the hematologic presentation of autoimmune gastritis (AIG) is age-related and progresses from iron-deficiency to cobalamin depletion. This study is an important contribution to the understanding of the natural history of AIG. We wish to comment on aspects that are related to Helicobacter pylori and may have clinical relevance.

The relation between H pylori and AIG is not fully understood. AIG is mediated by CD4⁺ T cells reactive to the H⁺K⁺-ATPase, and H pylori probably triggers the autoimmune process by molecular mimicry.²  Hershko and colleagues¹  provide strong epidemiologic evidence in support of this model. In their study, almost 90% of AIG patients younger than 20 years were infected. The low prevalence of infection among old patients with pernicious anemia (12%) does not argue against a relation of H pylori to AIG, but can be explained by the observation that the microenvironment of the atrophic stomach is hostile to the growth and colonization of H pylori, with progressive atrophy leading to a loss of the bacterial niche.³  Indeed, in patients with pernicious anemia an anti–Helicobacter–immunoglobulin G (IgG) seroreversion rate of 6% per year has been observed.³ 

Although H pylori is potentially involved in the induction of AIG and has its own inhibitory effect on cobalamin absorption,⁴  there are no recommendations for the management of infection in AIG. The observations of Hershko and colleagues that iron-deficiency anemia (IDA) is the presenting feature in more than 50% of patients with AIG, and that these patients are mainly young and H pylori–positive, provides a basis for new therapeutic considerations. In AIG, IDA develops mainly as a consequence of reduced acid secretion. Acid is indispensable for solubilization, reduction, and subsequent absorption of nonheme dietary iron. Several lines of evidence suggest that AIG patients with IDA would benefit from H pylori eradication: (1) H pylori suppresses acid secretion through induction of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), which are potent inhibitors of gastric parietal and enterochromaffin-like (ECL) cell function.^5-8 H pylori causes loss of acid secreting parietal cells through induction of apoptosis.⁹  Thus, hypochlorhydria and atrophy, main features of AIG, are synergistically promoted by H pylori. (2) Eradication of infection restores acid secretion even in patients with severe atrophy.⁷  (3) H pylori inhibits secretion of ascorbic acid into the gastric juice, another important factor for iron absorption. (4) Recent studies show an association of H pylori with unexplained IDA, and antibiotic treatment frequently leads to improvement of this disease.¹⁰  Therefore, the new guidelines of the European Helicobacter pylori Study Group for the management of infection recommend bacterial eradication in unexplained IDA.¹¹ 

Long-term prospective studies are needed to define the influence of H pylori eradication on the presentation and progression of AIG. Currently available data, however, suggest that at least in AIG patients with IDA, diagnosis and treatment of infection would be beneficial. Finally, the recognition of AIG¹  and H pylori¹⁰  as possible causes of iron deficiency will probably have a strong impact on the clinical management of unexplained IDA.