Immune mechanisms of fibrosis and inflammation in IgG4-related disease

Curr Opin Rheumatol. 2020 Mar;32(2):146-151. doi: 10.1097/BOR.0000000000000686.


Purpose of review: To summarize recent advances in the understanding of the pathogenesis of IgG4-related disease.

Recent findings: Limited data exist to explain genetic susceptibility to IgG4-related disease and the underlying triggers for this disease have not yet been identified. Cytotoxic CD4 T cells and activated B cells infiltrate affected organs and express proinflammatory and profibrotic molecules. Antigen presented by activated B cells likely reactivates cytotoxic CD4 T cells in disease tissues and these T cells in turn induce the targeted apoptotic death of host cells in certain organs - which presumably present the same antigenic peptide on human leukocyte antigen class II molecules of relevance that was also presented on B cells during reactivation. A subsequent exaggerated tissue remodeling process is orchestrated by cytokines, chemokines, and enzymes secreted by both activated B cells and CD4CTLs. These molecules induce an overexuberant repair process resulting in fibrosis and loss of target organ function.

Summary: In IgG4-related disease, presumably self-reactive cytotoxic CD4 T cells infiltrate tissues, are reactivated by T cells and induce apoptotic death. Molecules secreted by activated B cells and by CD4CTLs drive an exaggerated wound healing response resulting in fibrosis and compromised tissue function.

Publication types

  • Review

MeSH terms

  • B-Lymphocytes / immunology*
  • Fibrosis / immunology
  • Fibrosis / pathology
  • Humans
  • Immunoglobulin G / immunology*
  • Immunoglobulin G4-Related Disease / immunology*
  • Immunoglobulin G4-Related Disease / pathology
  • Inflammation / immunology
  • Inflammation / pathology
  • Lymphocyte Activation / immunology


  • Immunoglobulin G