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Waht is IgG4 Waht is IgG4

Discover the science behind IgG4-RD pathophysiology

Understanding IgG4-RD Pathophysiology Understanding IgG4-RD Pathophysiology

B-Cells Play an Important Role in the IgG4-RD Immunopathogenesis19

B-Cells, Including Plasmablasts and Plasma Cells, Promote Inflammation and Fibrosis That Drives IgG4-RD19,20

Tissue Inflammation Tissue Inflammation

Image adopted from Lanzillotta et al9,20, Della-Torre et al17, and Maehara et al.19

  • 1 Plasmablasts undergo IgG4 class switch and oligoclonal expansion, leading to increased circulating plasmablasts and IgG4.23*
  • 2Plasmablasts activate CD4+ and CD8+ T cells which turn into cytotoxic T lymphocytes (CTLs) and cytolitic and pro-fibrotic molecules (IL-1β, IL-6, TGFβ, IFNγ).9,20,22
Tissue Fibrosis Tissue Fibrosis
  • 3 Plasmablasts secrete collagenous proteins and molecules that stimulate fibroblasts into secreting collagen.19
  • 4Plasmablasts secrete enzymes that crosslink collagen molecules, regulating extracellular matrix stiffness.19
  • 5Plasmablasts secrete chemokines, attracting inflammatory cells (e.g., CD4+ CTLs, eosinophils, and M2 macrophages) and further stimulating fibroblasts to secrete these chemokines.19

B-cells that drive IgG4-RD express specific cell markers, including CD197

Discover the science behind IgG4-RD pathophysiology

  • CD19 in IgG4-RD

    CD19 Is Expressed Widely Across the B-Cell Lineage24

    CD19 in IgG4-RD CD19 in IgG4-RD

    CD19+ plasmablasts and plasma cell levels increase
    during IgG4-RD flares.

    CD, cluster of differentiation; IgD, immunoglobulin D; IgM, immunoglobulin M; IgG, immunoglobulin G; IgG4, immunoglobulin 4; IgG4-RD, immunoglobulin
    G4–related disease.

Over time, IgG4-RD-driven inflammation and progressive fibrosis can lead to organ dysfunction and failure—early recognition of disease manifestation and intervention are key to preventing irreversible damage.6

Learn about the multiple ways that
IgG4-RD can manifest

* 60–70% of patients with IgG4-RD have elevated serum IgG4.
CCL, CC chemokine ligand; CD, cluster of differentiation; CTL, cytotoxic T lymphocyte; Ig, immunoglobulin; IGF, insulin-like growth factor; IFN, interferon; IgG1, immunoglobulin 1; IgG4-RD, immunoglobulin 4; IgG4-RD, immunoglobulin G4–related disease; IL, interleukin; IFN, interferon; LOXL2, lysyl oxidase-like 2; PDGF-B, platelet-derived growth factor B; Th2, T helper 2; Treg, regulatory T cell. IgG4, immunoglobulin 4; TGF, transforming growth factor.

  • References:

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