Clinical features and biomarker research advances in immunoglobulin 4-related digestive system disorders

Figure 1 Presents differences in the location of plasma cell infiltration between gastritis caused by Helicobacter pylori and immunoglobulin G4-related gastrointestinal disease. IgG4: Immunoglobulin G4.

Figure 2 Algorithmic flowchart for pancreatobiliary differentiation: Integrating translational biomarkers to exclude malignancy. IgG4: Immunoglobulin G4; CT: Computed tomography; MRI: Magnetic resonance imaging; ULN: Upper limit of normal; TARC: Thymus and activation-regulated chemokine; Tph: Peripheral helper T cells; IgG4-DSD: Immunoglobulin G4-related digestive system disorders; EUS-FNA/FNB: Endoscopic ultrasound-guided fine-needle aspiration/fine-needle biopsy; ERCP: Endoscopic retrograde cholangiopancreatography; MDT: Multidisciplinary team; IFN: Interferon; IL: Interleukin.

Figure 3 Schematic diagram of the immunopathogenic cascade in immunoglobulin G4-related digestive system disorders. The inflammatory process is initiated by antigen presentation involving M2-polarized macrophages and plasmacytoid dendritic cells (pDCs). Activated pDCs secrete interferon-α and interleukin (IL)-33, establishing a pro-fibrotic microenvironment. Naïve CD4⁺ T cells differentiate into distinct pathogenic subsets: Th2 cells (producing IL-4/IL-13), T follicular helper cells (producing IL-21), and the recently identified peripheral helper T cells (CD4⁺CXCR5^-PD-1^hi). These T cell subsets promote the massive expansion of B cells and their class-switching to IgG4-secreting plasma cells via IL-4 and IL-21 signaling. Finally, storiform fibrosis is orchestrated by transforming growth factor-β (secreted by M2 macrophages) and the IL-33/ST2 axis, which activates fibroblasts and mast cells. Chemokines such as thymus and activation-regulated chemokine (CCL17) and CCL18 further recruit lymphocytes, perpetuating the cycle of chronic inflammation. IgG4: Immunoglobulin G4; IgG4-RD: Immunoglobulin G4-related disease; TARC: Thymus and activation-regulated chemokine; IL: Interleukin; TGF-β: Transforming growth factor β; Treg: Regulatory T cells.