Oxyntic Gland Intraepithelial T Lymphocytes as Progression Marker of Potential Autoimmune Gastritis

Autoimmune gastritis (AIG) is a chronic immune-mediated disease with potential for serious clinical consequences, yet early identification remains challenging. We aimed to assess whether deep oxyntic gland intraepithelial CD3 + T lymphocytosis may serve as a predictive histological marker of progression from potential -i.e., parietal cell antibody-positive patients without baseline gastric atrophy- to overt AIG.

We prospectively enrolled 45 adult parietal cell antibody-positive patients without histological evidence of mucosal atrophy between 2020 and 2022. All underwent upper gastrointestinal endoscopy with biopsies, and deep CD3 + intraepithelial lymphocytes (IELs) were quantified by immunohistochemistry. Patients were followed clinically and endoscopically for a median of 25 months. The primary end point was progression to overt AIG, defined histologically. Receiving operator curve analysis determined the optimal IEL cutoff for predicting progression. Gastrin-17 levels were assessed at baseline and follow-up.

Thirteen of 45 patients (28.9%) progressed to overt AIG. Progressors had significantly higher baseline deep CD3 + IEL counts (median 12.2 vs 3.9 per 100 epithelial cells, P < 0.01). A threshold of >7.1 IELs/100 cells yielded 92.3% sensitivity and 87.5% specificity (area under curve = 0.97). Baseline gastrin-17 levels did not differ significantly, but follow-up levels were markedly elevated in progressors (median 248 vs 37.4 pg/mL, P < 0.01). Patients who have not yet progressed are being followed up.

Deep intraepithelial CD3 + lymphocytosis in the oxyntic mucosa is a strong predictor of AIG progression in patients with potential AIG. According to our preliminary results, IEL quantification should be considered in routine histological assessment to guide early risk stratification and follow-up strategies in potential AIG.