Journal of Gastroenterology

, Volume 46, Issue 3, pp 277–288 | Cite as

Recent advances in the concept and diagnosis of autoimmune pancreatitis and IgG4-related disease

  • Kazuichi Okazaki
  • Kazushige Uchida
  • Masanori Koyabu
  • Hideaki Miyoshi
  • Makoto Takaoka


Recent studies have suggested the existence of two subtypes of autoimmune pancreatitis (AIP): type 1 AIP, related to IgG4 (lymphoplasmacytic sclerosing pancreatitis); and type 2 AIP, related to a granulocytic epithelial lesion (idiopathic duct-centric chronic pancreatitis). Compared with type 2 AIP, the clinicopathological features of type 1 AIP, with increased serum IgG4/IgE levels, abundant infiltration of IgG4 + plasmacytes and lymphocytes, autoantibodies, and steroid responsiveness, are more suggestive of abnormal immunity such as allergy or autoimmunity. Moreover, patients with type 1 AIP often have extrapancreatic lesions, such as sclerosing cholangitis, sclerosing sialadenitis, or retroperitoneal fibrosis, showing pathological features similar to those of the pancreatic lesions. Based on these findings, an international concept of and diagnostic criteria for AIP have been proposed recently. Of interest, many synonyms have been proposed for the conditions of AIP and extrapancreatic lesions associated with IgG4, such as “multifocal idiopathic fibrosclerosis,” “IgG4-related autoimmune disease,” “IgG4-related sclerosing disease,” “systemic IgG4-related plasmacytic syndrome (SIPS),” and “IgG4-related multiorgan lymphoproliferative syndrome,” all of which may refer to the same conditions. Therefore, the Japanese Research Committee for “Systemic IgG4-Related Sclerosing Disease” proposed a disease concept and clinical diagnostic criteria based on the concept of multifocal fibrosclerosing disease, in 2009, in which the term “IgG4-related disease” was agreed upon as a minimal consensus to cover these conditions. Although the significance of IgG4 in the development of “IgG4-related disease” remains unclear, we have proposed a hypothesis for the development of type 1 AIP, one of the IgG4-related diseases. The concept and diagnostic criteria of “IgG4-related disease” will be changed in accordance with future studies.


IgG4 IgG4-related disease Autoimmune pancreatitis Mikulicz disease Regulatory T cell (Treg) 



Autoimmune pancreatitis


Anti-nuclear antibody


Carbonic anhydrase-II


Cytotoxic T lymphocyte antigen-4


Endoscopic retrograde cholangio-pancreatography










Lymphoplasmacytic sclerosing pancreatitis


Mikulicz disease


Major histocompatibility complex


Multiorgan lymphoproliferative disease


Plasminogen-binding protein


Sjögren’s syndrome


Primary sclerosing cholangitis


Rheumatoid factor


Systemic IgG4 plasmacytic syndrome


Systemic lupus erythematosus


Regulatory T cell


Ubiquitin-protein ligase E3 component n-recognin 2



This study was partly supported by a Grant-in-Aid for Scientific Research from the Ministry of Culture and Science of Japan (20590810), and a Grant-in-Aid for the “Research for Intractable Disease” Program from the Ministry of Health, Labor and Welfare of Japan.


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Copyright information

© Springer 2011

Authors and Affiliations

  • Kazuichi Okazaki
    • 1
  • Kazushige Uchida
    • 1
  • Masanori Koyabu
    • 1
  • Hideaki Miyoshi
    • 1
  • Makoto Takaoka
    • 1
  1. 1.Division of Gastroenterology and Hepatology, The Third Department of Internal MedicineKansai Medical UniversityHirakataJapan

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