Autoimmune Gastritis: Unveiling the Mystery

Abstract

Atrophic gastritis is primarily caused by Helicobacter pylori infection and autoimmune mechanisms. In South Korea, where H. pylori infections remain highly prevalent, standardized guidelines for the use of serological testing or biopsies for diagnosing autoimmune gastritis (AIG) have not been developed. Recently, as H. pylori infection rates have declined and trends associated with gastric cancer and gastric neuroendocrine neoplasms (gNENs) have shifted, interest in AIG has increased, particularly in Asia. However, AIG diagnoses are often delayed owing to a lack of suspicion; even when AIG is considered, the limited understanding of the disease hampers its accurate diagnosis. Furthermore, the absence of established treatments and standardized follow-up protocols pose significant challenges for patient management. The loss of gastric acid secretion, a critical component of digestive function, and destruction of the gastric corpus mucosa are caused by autoimmune mechanisms, leading to incomplete protein digestion, micronutrient deficiencies, gut microbiota imbalances, and elevated gastrin levels that eventually contribute to neoplastic lesions, such as gNENs and gastric cancer. Although AIG is an immunerelated gastrointestinal disorder, it intersects with various disciplines, including pathology, genetics, microbiology, endocrinology, hematology, and oncology, and many unresolved issues remain in these areas. Research to address unanswered questions about the disease pathogenesis, the relationship between AIG and H. pylori, appropriate diagnostic methods and the risk of gastric neoplasms has previously been published. This review provides an overview of the current findings and explores unanswered questions surrounding AIG to help elucidate its complex pathogenesis, clinical implications, and potential management strategies.

Keywords: Autoimmune diseases; Gastric parietal cells; Gastritis; Helicobacter pylori; Stomach neoplasms.

Fig. 1.

Pathogenetic interactions in autoimmune gastritis. This figure has been reproduced from Lenti et al. Nat Rev Dis Primers 2020;6:56 [3]., with permission of the Springer Nature. HCl, hydrogen chloride; ATPase, adenosine triphosphatase; MHC II, major histocompatibility complex class II; TCR, T cell receptor; FasL, Fas ligand; CD, cluster of differentiation; Th, helper T cell; IFN, interferon; TNF, tumor necrosis factor; IL, interleukin; TGF, tumor growth factor; PCA, anti-parietal cell antibody; IFA, intrinsic factor antibody.

Fig. 2.

Sixty-three-year-old woman with autoimmune gastritis, florid stage. Blood test results were as follows: pepsinogen I, 8.3 ng/mL; pepsinogen II, 12.3 ng/mL; pepsinogen I/II ratio, 0.7; serum gastrin, >1000 pg/mL; Helicobacter pylori antibody (IgG), equivocal; anti-parietal cell antibody, positive (1:80). A: The fundic mucosa is diffusely atrophic. B: The antral mucosa appears relatively normal. No endoscopic evidence of atrophy is seen (case and endoscopic images courtesy of Professor Jun Haeng Lee from the Department of Medicine at Sungkyunkwan University School of Medicine, Samsung Medical Center). C: The corporal mucosa shows extensive loss of oxyntic glands and lymphoplasmacytic infiltrates in the deeper portion of the mucosa (hematoxylin and eosin [H&E] staining, 4×). D: The atrophic corporal mucosa has been replaced by pyloric metaplasia, pancreatic metaplasia (white arrow), and intestinal metaplasia (black arrow) (H&E staining, 10×). E: Chromogranin immunohistochemistry demonstrates enterochromaffin-like cell hyperplasia (10×). F: The antral mucosa appears normal (H&E staining, 4×) (histological images courtesy of Professor Soomin Ahn from the Department of Pathology and Translational Genomics at Sungkyunkwan University School of Medicine, Samsung Medical Center).

Fig. 3.

Endoscopic findings in the early stage of autoimmune gastritis. A: A bamboo joint-like appearance is observed in the greater curvature of the gastric body. B: Pseudopolyps are observed in the greater curvature of the gastric body.

Fig. 4.

Flowchart for the diagnosis of autoimmune gastritis. DM, diabetes mellitus; GERD, gastroesophageal reflux disease.