Biomarkers in autoimmune pancreatitis and immunoglobulin G4-related disease

Figure 1 Immunopathogenesis of autoimmune pancreatitis and immunoglobulin G4-related disease. Plasmacytoid dendritic cells produce interferon-α and interleukin-33 and thereby mediate chronic fibroinflammatory responses in the pancreas. T helper type 2 cells expressing GATA-binding protein 3, regulatory T cells expressing forkhead box P3, follicular helper T cells expressing B cell lymphoma 6, and CD4⁺ cytotoxic T cells expressing T-box-expressed-in-T-cells are involved in the development of autoimmune pancreatitis and immunoglobulin G4-related disease. IgG4: Immunoglobulin G4; pDCs: Plasmacytoid dendritic cells; IFN: Interferon; IL: Interleukin; Th2: T helper type 2 cells; Tregs: Regulatory T cells; GATA3: GATA-binding protein 3; FOXP3: Forkhead box P3; Tfh: Follicular helper T; BCL6: B cell lymphoma 6; T-bet: T-box-expressed-in-T-cells.

Figure 2 Biomarkers in autoimmune pancreatitis and immunoglobulin G4-related disease. Left panel: Interferon-a (IFN-α) is produced by plasmacytoid dendritic cells (pDCs). Interleukin-33 (IL-33) is produced by pDCs and macrophages. B cell-activating factor (BAFF) is produced by pDCs, monocytes, and basophils; Right panel: IL-4, IL-5, and IL-13 are produced by T helper type 2 cells expressing GATA-binding protein 3 (GATA3). IL-10 and transforming growth factor-β1 (TGF-β) are produced by regulatory T cells (Tregs) expressing forkhead box P3. IL-21 is produced by follicular helper T cells expressing B cell lymphoma 6. TGF-β is produced by Tregs and CD4⁺ cytotoxic T cells (CTLs) expressing T-box-expressed-in-T-cells. IFN-γ is produced by CD4⁺ CTLs. Plasma cells produce immunoglobulin G1 (IgG1) and IgG4 Ab. These cytokines are possible biomarkers for autoimmune pancreatitis and IgG4-related disease. IgG: Immunoglobulin G; pDCs: Plasmacytoid dendritic cells; IFN: Interferon; IL: Interleukin; BAFF: B cell-activating factor; Th2: T helper type 2 cells; Tregs: Regulatory T cells; GATA3: GATA-binding protein 3; FOXP3: Forkhead box P3; Tfh: Follicular helper T; BCL6: B cell lymphoma 6; T-bet: T-box-expressed-in-T-cells; CTLs: CD4⁺ cytotoxic T cells.

Figure 3 Diagnostic algorithm for autoimmune pancreatitis and immunoglobulin G4-related disease. Serum concentration of cytokines and chemokines or the presence of serum auto-antibodies may be useful for diagnosis of autoimmune pancreatitis and immunoglobulin G4 (IgG4)-related disease displaying normal or slightly elevated concentrations of IgG4. AIP: Autoimmune pancreatitis; IgG4-RD: Immunoglobulin G4-related disease; IFN: Interferon; IL: Interleukin; BAFF: B cell-activating factor; CCL17: C-C motif chemokine ligand 17.