CASE REPORT article
Front. Oncol.
Sec. Gastrointestinal Cancers: Gastric and Esophageal Cancers
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1644263
Zolbetuximab-Induced Gastritis with Protein-Losing Gastroenteropathy and Hypogammaglobulinemia: A Case Implicating IgA Vasculitis
Provisionally accepted
Yasuhiro Mitsui
Yasushi Sato*
Ryo Shinomiya
Satoshi Sumida
Shota FujimotoAkiko OkadaTakeshi MitsuhashiTomoyuki KawaguchiKaizo KagemotoYoshifumi KidaKoichi OkamotoHisanori Uehara
Tetsuji Takayama*- Tokushima University, Tokushima, Japan
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
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 41year-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⁺ lymphocytes into the stroma and CD8⁺ lymphocytes into both the epithelium and stroma, as well as IgA deposition along interstitial capillaries. Protein leakage from the stomach was confirmed by ⁹⁹ᵐTc-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's 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.
Keywords: gastric cancer, zolbetuximab, Claudin-18.2, Gastritis, Protein-losing gastroenteropathy, hypogammaglobulinemia, Hypoalbuminemia, IgA vasculitis
Received: 10 Jun 2025; Accepted: 30 Jun 2025.
Copyright: © 2025 Mitsui, Sato, Shinomiya, Sumida, Fujimoto, Okada, Mitsuhashi, Kawaguchi, Kagemoto, Kida, Okamoto, Uehara and Takayama. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yasushi Sato, Tokushima University, Tokushima, Japan
Tetsuji Takayama, Tokushima University, Tokushima, Japan
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.