{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T15:53:03Z","timestamp":1790610783509,"version":"4.1.0"},"reference-count":21,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T00:00:00Z","timestamp":1753660800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Zolbetuximab (ZOL), a monoclonal antibody targeting Claudin-18.2, is a promising therapeutic agent for the treatment of advanced gastric cancer. We report the first case of ZOL-induced acute gastritis leading to protein-losing gastroenteropathy, characterized by severe hypogammaglobulinemia and hypoalbuminemia, possibly mediated by IgA vasculitis. A 41-year-old woman with metastatic Claudin-18.2-positive gastric cancer was treated with ZOL in combination with chemotherapy. On day 8 of the second treatment cycle, she developed severe gastrointestinal symptoms and immunologic abnormalities. Laboratory tests revealed marked hypogammaglobulinemia (IgG 193 mg\/dL) and hypoalbuminemia (albumin 1.9 g\/dL). Esophagogastroduodenoscopy showed severe acute gastritis, and biopsy specimens demonstrated infiltration of CD4<jats:sup>+<\/jats:sup> lymphocytes into the stroma and CD8<jats:sup>+<\/jats:sup> lymphocytes into both the epithelium and stroma, as well as IgA deposition along interstitial capillaries. Protein leakage from the stomach was confirmed by <jats:sup>99m<\/jats:sup>Tc-HSA-D scintigraphy. These findings suggest that ZOL-induced mucosal injury and increased vascular permeability, likely driven by an IgA-mediated vasculitic mechanism, contributed to the protein loss. The patient\u2019s symptoms and laboratory abnormalities improved with supportive care. Upon ZOL rechallenge, gastrointestinal symptoms and protein loss recurred in a milder form, reinforcing a causal relationship. This case highlights a novel pathophysiological link between ZOL-induced gastritis and systemic immunoglobulin loss, underscoring the importance of careful monitoring of serum protein levels during ZOL therapy. Further studies are warranted to elucidate the immune-mediated mechanisms and optimize management strategies.<\/jats:p>","DOI":"10.3389\/fonc.2025.1644263","type":"journal-article","created":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T09:04:08Z","timestamp":1753693448000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Case Report: Zolbetuximab-induced gastritis with protein-losing gastroenteropathy and hypogammaglobulinemia: a case implicating IgA 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