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Publications

Journal Article Ahead of print

PubMed: 41666976 DOI: 10.1016/j.amjmed.2026.02.005

Serum gastrin levels, stratified on PPI use, improve diagnosis of pernicious anemia in the absence of intrinsic factor antibodies.

Am J Med

Authors: Valentin Lacombe, Emeline Vinatier, Jade Aurrière, Odile Blanchet, Cédric Annweiler, Christian Lavigne, Pascal Reynier, Geoffrey Urbanski

Affiliations

  • Service de Médecine interne et polyvalente, Centre Hospitalier du Haut-Anjou, Château-Gontier, France; Univ Angers, Inserm, CNRS, MITOVASC, Equipe MitoLab, SFR ICAT, F-49000 Angers, France; Service de Médecine interne et Immunologie clinique, Centre Hospitalier Universitaire d'Angers, Angers, France.
  • Laboratoire d'Immunologie, Centre Hospitalier Universitaire d'Angers, Angers, France; Univ Angers, Nantes Université, Inserm, CNRS, CRCI2NA, SFR ICAT, F-49000 Angers, France.
  • Univ Angers, Inserm, CNRS, MITOVASC, Equipe MitoLab, SFR ICAT, F-49000 Angers, France.
  • Centre de Ressources Biologiques, Centre Hospitalier Universitaire d'Angers, Angers, France, BB-0033-00038.
  • Service de Médecine Gériatrique, Centre Hospitalier Universitaire d'Angers, Angers, France; UNIV ANGERS, UR 4638, Laboratoire de Psychologie des Pays de la Loire, Angers, France.
  • Service de Médecine interne et Immunologie clinique, Centre Hospitalier Universitaire d'Angers, Angers, France.
  • Laboratoire de Biochimie et biologie moléculaire, Centre Hospitalier Universitaire d'Angers, Angers, France.
  • Service de Médecine interne et Immunologie clinique, Centre Hospitalier Universitaire d'Angers, Angers, France; Service d'Immunologie et d'allergologie, Hôpitaux universitaires de Genève, Genève, Suisse; Department of Orofacial Sciences, University of California, San Francisco, CA, United States.

Abstract

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.

MeSH

Cells, Pepsinogen A, Anemia, Pernicious, Serum, Absenteeism, Antibodies, Anemia, Chromogranins, Biomarkers, Diagnosis, Intrinsic Factor