{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T15:06:48Z","timestamp":1793200008817,"version":"4.5.0"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T00:00:00Z","timestamp":1770249600000},"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. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Immunoglobulin G4-related sclerosing cholangitis (IgG4-SC), also termed IgG4-related cholangitis (IRC), is a challenging immune-mediated biliary disease, frequently mimicking malignancies such as cholangiocarcinoma (CCA) or other sclerosing cholangitides like primary sclerosing cholangitis (PSC). Accurate diagnosis is critical to avoid unnecessary surgical interventions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This mini-review aims to synthesize the most current evidence on the pathogenesis, diagnostic pitfalls, and management strategies for IgG4-SC, with a focused discussion on overcoming diagnostic dilemmas and addressing the significant challenge of disease relapse.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key findings<\/jats:title>\n                    <jats:p>The pathogenesis of IgG4-SC involves a complex interplay of genetic predisposition, environmental triggers (e.g., industrial vapors, dust, gases, fumes, and asbestos), and dysregulated adaptive immunity. A distinctive CD4+ T-cell response, dominated by T-helper 2 (Th2), follicular helper T (Tfh) cells, and regulatory T cells (Tregs), drives B-cell activation, oligoclonal expansion of IgG4+ plasmablasts, and progressive fibrosis. Notably, the discovery of IgG4\/IgG1 autoantibodies against annexin A11 and laminin 511-E8 has provided insight into potential direct pathogenic mechanisms. Diagnosis relies on a multimodal approach integrating clinical presentation, characteristic imaging findings, elevated serum IgG4 levels (with levels &amp;gt;2\u00d7 ULN being suggestive, and &amp;gt;4\u00d7 ULN being highly specific), the IgG4\/IgG1 ratio (&amp;gt;0.24), other organ involvement (notably type 1 autoimmune pancreatitis, AIP), supportive histopathology, and a rapid response to corticosteroid therapy. Despite high initial response rates to steroids, relapse occurs in 30%\u201350% of patients. Maintenance therapy with steroid-sparing immunomodulators (e.g., azathioprine, mycophenolate mofetil) or B-cell depleting agents such as rituximab is often required. The anti-CD19 monoclonal antibody inebilizumab has emerged as a potent new option for maintaining remission.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Maintaining a high index of clinical suspicion for IgG4-SC is essential in patients with obstructive jaundice and biliary strictures. Future efforts should focus on validating specific biomarkers (e.g., circulating plasmablasts, autoantibody profiles) and developing evidence-based protocols for long-term management to prevent fibrotic complications and reduce the relapse rate.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1732637","type":"journal-article","created":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T06:45:15Z","timestamp":1770273915000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["IgG4-related sclerosing cholangitis: navigating diagnostic dilemmas and the challenge of relapse"],"prefix":"10.3389","volume":"13","author":[{"given":"Xiangxiang","family":"Ren","sequence":"first","affiliation":[{"name":"Department of General Surgery, Affiliated Hospital of Hebei University, Baoding","place":["Hebei, 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