Autoimmune Gastritis (AIG) is a chronic, progressive condition where the body’s immune system mistakenly targets the acid-producing parietal cells in the gastric corpus and fundus. This destruction leads to chronic inflammation and gradual atrophy, or thinning, of the stomach mucosa. Because this process is insidious, AIG often remains asymptomatic in its early stages, resulting in a delayed diagnosis. Accurate identification requires a sequential, multi-step diagnostic process moving from initial suspicion to definitive confirmation.
Initial Clinical Assessment and Differential Diagnosis
The journey toward an AIG diagnosis typically begins when a patient presents with vague symptoms or abnormal blood test results suggesting a deficiency. Common complaints that prompt investigation include persistent fatigue, weakness, dizziness, or heart palpitations, often linked to anemia. The physical examination is usually non-contributory in uncomplicated cases, though a doctor may check for signs like a pale appearance or epigastric tenderness.
A physician must first use differential diagnosis to rule out more common causes of gastric inflammation. The most frequent cause of atrophic gastritis is a long-term Helicobacter pylori infection, which typically affects the antrum first. Ruling out this bacterial infection, often through breath or stool tests, is an important early step because its management differs significantly from AIG. Once other environmental and infectious triggers are excluded, clinical suspicion for AIG, which is characterized by corpus-restricted atrophy, increases enough to order specific serological tests.
Serological Testing for Autoantibodies and Biomarkers
The next phase involves non-invasive serological testing, which screens the blood for markers of the autoimmune attack and resulting nutrient malabsorption. The primary targets are two specific autoantibodies: Parietal Cell Antibodies (PCA) and Intrinsic Factor Antibodies (IFA). PCA targets the H+/K+-ATPase proton pump and is found in 60% to 90% of AIG patients.
While PCA is sensitive for AIG, IFA is considered more specific for pernicious anemia, a condition that frequently co-occurs with the disease. Intrinsic factor is produced by parietal cells and is necessary for Vitamin B12 absorption; IFA directly blocks this function. IFA is present in 30% to 50% of patients, but its presence strongly supports the diagnosis of advanced AIG with B12 malabsorption.
The destruction of parietal cells impairs stomach acid production, leading to measurable deficiencies. Low serum Vitamin B12 levels are a hallmark of advanced AIG due to the lack of intrinsic factor. Elevated levels of methylmalonic acid (MMA) and homocysteine are also measured, as these compounds accumulate when B12 is deficient, providing a sensitive indicator of the deficiency’s functional impact. Furthermore, the lack of stomach acid impairs iron absorption, meaning many AIG patients also present with iron deficiency anemia and low ferritin levels.
Definitive Confirmation Through Endoscopy and Biopsy
Although serology provides strong evidence, the definitive diagnosis of Autoimmune Gastritis relies on a histological examination of the stomach lining. This requires an upper endoscopy, where a flexible tube with a camera is passed into the stomach to visually inspect the mucosa. During the procedure, the physician takes tissue samples, or biopsies, from specific areas of the stomach, typically the gastric corpus and antrum, following standardized protocols.
Visual inspection during endoscopy may reveal subtle signs of AIG, such as a pale appearance or increased visibility of submucosal blood vessels due to mucosal thinning. However, these visual findings are not reliable enough alone, making the biopsy necessary to visualize microscopic changes. The pathologist examines the tissue to confirm the characteristic physical damage caused by the autoimmune process.
The hallmark histological finding of AIG is atrophy—the loss of specialized glands, including parietal cells, specifically in the corpus and fundus. This atrophy is accompanied by a dense infiltration of chronic inflammatory cells, predominantly lymphocytes. A key feature distinguishing AIG is that the inflammation and atrophy are typically restricted to the body and fundus, while the antrum is spared.
As the normal oxyntic glands are destroyed, the stomach lining may attempt to heal by transforming into cell types that resemble other parts of the digestive tract, a process known as metaplasia. Common findings in advanced AIG include pseudopyloric metaplasia (cells resembling the pyloric region) and intestinal metaplasia (cells resembling intestinal cells). The combination of corpus-restricted atrophy, inflammatory infiltrate, and metaplasia provides the conclusive evidence needed to confirm the diagnosis.