The American journal of medicine · 2026
Serum gastrin levels, stratified on PPI use, improve diagnosis of pernicious anemia in the absence of intrinsic factor antibodies.
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Lacombe Valentin, Vinatier Emeline, Aurrière Jade, Blanchet Odile, Annweiler Cédric, Lavigne Christian, Reynier Pascal, Urbanski Geoffrey
Аннотация
BACKGROUND: Diagnosis of pernicious anemia remains challenging in patients with vitamin B12 deficiency and isolated anti-parietal cell antibodies (APCA) because of their limited specificity. Prior biomarker studies mostly excluded patients receiving proton pump inhibitors (PPIs). We aimed to assess the diagnostic performance of pernicious anemia biomarkers while accounting for PPI use.
METHODS: We prospectively enrolled 86 patients with B12 deficiency, categorized into three groups: confirmed pernicious anemia with intrinsic factor antibodies (IFA group), suspected pernicious anemia with APCA only (APCA group), and non-pernicious anemia controls with chronic PPI use (PPI group). Serum gastrin, chromogranin A, pepsinogen I and II, and ghrelin were evaluated, with analyses stratified by PPI use.
RESULTS: Among APCA patients, both gastrin and chromogranin A were associated with pernicious anemia, but were strongly correlated. Gastrin was the most informative biomarker and remained independently associated with pernicious anemia. PPI use significantly affected gastrin levels, supporting stratified thresholds. Diagnostic accuracy of gastrin was excellent (AUC 0.98 without PPI; 0.88 with PPI), with optimal thresholds of ≥ 75 pg/mL (Se 92%, Sp 100%) without PPI and ≥ 500 pg/mL (Se 67%, Sp 96%) with PPI.
CONCLUSION: In B12 deficient patients with isolated APCA, gastrin improves non-invasive diagnosis of pernicious anemia and may reduce the need for endoscopy by helping exclude the diagnosis.
METHODS: We prospectively enrolled 86 patients with B12 deficiency, categorized into three groups: confirmed pernicious anemia with intrinsic factor antibodies (IFA group), suspected pernicious anemia with APCA only (APCA group), and non-pernicious anemia controls with chronic PPI use (PPI group). Serum gastrin, chromogranin A, pepsinogen I and II, and ghrelin were evaluated, with analyses stratified by PPI use.
RESULTS: Among APCA patients, both gastrin and chromogranin A were associated with pernicious anemia, but were strongly correlated. Gastrin was the most informative biomarker and remained independently associated with pernicious anemia. PPI use significantly affected gastrin levels, supporting stratified thresholds. Diagnostic accuracy of gastrin was excellent (AUC 0.98 without PPI; 0.88 with PPI), with optimal thresholds of ≥ 75 pg/mL (Se 92%, Sp 100%) without PPI and ≥ 500 pg/mL (Se 67%, Sp 96%) with PPI.
CONCLUSION: In B12 deficient patients with isolated APCA, gastrin improves non-invasive diagnosis of pernicious anemia and may reduce the need for endoscopy by helping exclude the diagnosis.