IgG4-Related Disease Diagnosis and Management

IgG4-related disease (IgG4-RD) is a systemic fibroinflammatory condition marked by tissue infiltration of IgG4-secreting plasma cells and varying degrees of fibrosis. It may involve the pancreas, biliary tract, retroperitoneum, salivary glands, large vessels and more. Diagnosis requires integration of clinical presentation, characteristic imaging features, elevated serum IgG4 and hallmark histopathological findings. Early recognition and distinction from mimicking conditions are critical to prevent irreversible organ damage. First-line management consists of glucocorticosteroids for remission induction, followed by immunomodulators or B-cell depletion therapy for maintenance and relapse prevention. Ongoing research has elucidated molecular pathways driving fibrosis and inflammation, refined diagnostic imaging techniques and identified novel biomarkers to enable more personalised treatment strategies. A multidisciplinary approach underpins optimal long-term outcomes worldwide.

Research from Nature Portfolio

Recent studies have unveiled a central role for ubiquitin-specific protease 25 (USP25) in IgG4-RD pathogenesis. Reduced USP25 expression in patient immune cells and knockout models was shown to enhance SMAD3 signalling, driving tissue fibrosis, while simultaneously promoting interleukin-1β–mediated inflammation. Loss of USP25 also led to ubiquitination and degradation of RAC1, altering glycolytic pathways, and diminished LYN expression, impacting B-cell activation. These insights position USP25 as both a promising diagnostic marker and a potential therapeutic target for modulating the dual fibroinflammatory phenotype of IgG4-RD.

IgG4-Related Disease Diagnosis and Management publication trend

The graph below shows the total number of articles in igg4-related disease diagnosis and management across all publications each year (not limited to Nature Index journals).

Technical terms

IgG4-related disease (IgG4-RD): A multisystem disorder characterised by fibrotic lesions and infiltration by IgG4-secreting plasma cells.

Plasmablasts: Short-lived, proliferating B-cell precursors that secrete antibodies and serve as markers of active IgG4-RD.

Ubiquitin-specific protease 25 (USP25): An enzyme that removes ubiquitin from proteins; its downregulation in IgG4-RD enhances profibrotic and proinflammatory pathways.

18F-FDG PET/CT: A metabolic imaging technique using fluorodeoxyglucose to detect and quantify inflammatory and fibrotic lesions in IgG4-RD.

Glucocorticosteroids: Anti-inflammatory agents used as first-line therapy to induce remission in IgG4-RD by suppressing immune-mediated tissue injury.

B-cell depletion therapy: Treatment, typically with rituximab, targeting CD20+ B cells to reduce plasmablast formation and maintain disease remission.

References

1. A novel clinical entity, IgG4-related disease (IgG4RD): general concept and details. Modern Rheumatology (2011).
2. Expression of USP25 associates with fibrosis, inflammation and metabolism changes in IgG4-related disease. Nature Communications (2024).
3. IgG4-related cholangitis – a mimicker of fibrosing and malignant cholangiopathies. Journal of Hepatology (2023).
4. Characterizing IgG4-related disease with 18F-FDG PET/CT: a prospective cohort study. European Journal of Nuclear Medicine and Molecular Imaging (2014).
5. Long-term efficacy and safety of rituximab in IgG4-related disease: Data from a French nationwide study of thirty-three patients. PLOS ONE (2017).