Pan Y, Jiang YZ. Clinical features and biomarker research advances in immunoglobulin 4-related digestive system disorders. World J Gastroenterol 2026; 32(23): 118782 [DOI: 10.3748/wjg.v32.i23.118782]
Corresponding Author of This Article
Yu-Zhang Jiang, Professor, Department of Laboratory Medicine, The Affiliated Huai’an No. 1 People’s Hospital of Nanjing Medical University, No. 1 West Huanghe Road, Huai’an 223300, Jiangsu Province, China. jyz8848@163.com
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Gastroenterology & Hepatology
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review-article
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Pan Y, Jiang YZ. Clinical features and biomarker research advances in immunoglobulin 4-related digestive system disorders. World J Gastroenterol 2026; 32(23): 118782 [DOI: 10.3748/wjg.v32.i23.118782]
World J Gastroenterol. Jun 21, 2026; 32(23): 118782 Published online Jun 21, 2026. doi: 10.3748/wjg.v32.i23.118782
Clinical features and biomarker research advances in immunoglobulin 4-related digestive system disorders
Yue Pan, Yu-Zhang Jiang
Yue Pan, Yu-Zhang Jiang, Department of Laboratory Medicine, The Affiliated Huai’an No. 1 People’s Hospital of Nanjing Medical University, Huai’an 223300, Jiangsu Province, China
Author contributions: Pan Y was responsible for the literature review, data collection, and drafting the manuscript; Jiang YZ was responsible for conceptualization, review, and editing. All authors have read and approved the final manuscript.
AI contribution statement: During the preparation of this work, the authors used ChatGPT in order to improve language. After using this tool, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication.
Supported by Open Research Project of the Huai’an ‘Tian Yixing’ Key Laboratory of Medical Laboratory Science, No. HAP202004.
Conflict-of-interest statement: The authors declare no conflict of interest.
Corresponding author: Yu-Zhang Jiang, Professor, Department of Laboratory Medicine, The Affiliated Huai’an No. 1 People’s Hospital of Nanjing Medical University, No. 1 West Huanghe Road, Huai’an 223300, Jiangsu Province, China. jyz8848@163.com
Received: January 12, 2026 Revised: January 31, 2026 Accepted: March 16, 2026 Published online: June 21, 2026 Processing time: 148 Days and 21.2 Hours
Abstract
Immunoglobulin G4 (IgG4)-related disease is a systemic fibro-inflammatory condition characterized by tumefactive lesions, dense lymphoplasmacytic infiltration, and storiform fibrosis. Among its various presentations, IgG4-related digestive system disorders (IgG4-DSD) are the most prevalent, frequently mimicking malignancies and posing significant diagnostic challenges. This review synthesizes advances over the past five years in the clinical spectrum, pathogenesis, and biomarker landscape of IgG4-DSD. We detail the specific features of key manifestations, particularly type 1 autoimmune pancreatitis and IgG4-related sclerosing cholangitis, which often coexist and manifest as painless jaundice. Differentiating these from pancreatic cancer relies on identifying characteristic radiological signs, such as the “sausage-like” pancreatic enlargement, and excluding conditions like primary sclerosing cholangitis. Furthermore, we explore the immunopathogenic mechanisms driving tissue fibrosis, emphasizing the upregulation of Th2 cytokines [interleukin (IL)-4, IL-13] and the roles of T follicular helper cells and M2 macrophages. Recognizing the limitations of serum IgG4, including the prozone effect and potential false negatives, we critically evaluate novel biomarkers with higher sensitivity and specificity. Promising candidates include circulating plasmablasts (CD19+CD24−CD38hi), peripheral helper T cells, chemokines such as thymus and activation-regulated chemokine/CCL17, and the interferon-α/IL-33 axis. Integrating these novel markers with clinical and radiological findings is essential for early diagnosis, monitoring disease activity, and implementing personalized therapeutic strategies.
Core Tip: Given that immunoglobulin-related digestive system disorders frequently mimic malignancies, leading to misdiagnosis, this review systematically maps the clinical spectrum from classical (pancreato-biliary) to rare (esophageal/mesenteric) manifestations. A key highlight is the paradigm shift from single-marker diagnosis to multidimensional biomarker assessment (e.g., plasma blasts, interferon-α-interleukin-33 axis). It focuses on the utility of these novel markers in monitoring disease activity and predicting fibrosis, providing evidence-based strategies for early recognition and personalized management.
