IgG4-related disease

Annu Rev Pathol. 2014:9:315-47. doi: 10.1146/annurev-pathol-012513-104708. Epub 2013 Oct 2.


Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is an immune-mediated condition that can affect almost any organ and is now being recognized with increasing frequency. IgG4-RD is characterized by a lymphoplasmacytic infiltrate composed of IgG4(+) plasma cells, storiform fibrosis, obliterative phlebitis, and mild to moderate eosinophilia. The diagnosis of IgG4-RD unifies many eponymous fibroinflammatory conditions that had previously been thought to be confined to single organs. IgG4-RD lesions are infiltrated by T helper cells, which likely cause progressive fibrosis and organ damage. IgG4 antibodies are generally regarded as noninflammatory. Although autoreactive IgG4 antibodies are observed in IgG4-RD, there is no evidence that they are directly pathogenic. Rituximab-induced B cell depletion in IgG4-RD leads to rapid clinical and histological improvement accompanied by swift declines in serum IgG4 concentrations. Although IgG autoantibodies against various exocrine gland antigens have been described in IgG4-RD, whether they are members of the IgG4 subclass is unknown. The contribution of autoantibodies to IgG4-RD remains unclear.

Publication types

  • Review

MeSH terms

  • Autoantibodies / immunology
  • Autoimmune Diseases / blood
  • Autoimmune Diseases / immunology*
  • Autoimmune Diseases / pathology*
  • Fibrosis / pathology
  • Humans
  • Hypergammaglobulinemia
  • Immunoglobulin G / blood*
  • Immunoglobulin G / immunology*
  • Inflammation / blood
  • Inflammation / immunology*
  • Inflammation / pathology*
  • Plasma Cells / immunology
  • Plasma Cells / pathology
  • Serologic Tests


  • Autoantibodies
  • Immunoglobulin G