Oxyntic gland intraepithelial T lymphocytes as progression marker of potential autoimmune gastritis

Background: 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 (PCA)-positive patients without baseline gastric atrophy- to overt AIG. Methods: We prospectively enrolled 45 adult PCA-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 via immunohistochemistry. Patients were followed clinically and endoscopically for a median of 25 months. The primary endpoint was progression to overt AIG, defined histologically. ROC analysis determined the optimal IEL cut-off for predicting progression. Gastrin-17 levels were assessed at baseline and follow-up. Results: 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 (AUC=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. Conclusions: Deep intraepithelial CD3+ lymphocytosis in the oxyntic mucosa is a strong predictor of AIG progression in potential AIG patients. 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.