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
Review

Abstract

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.

Keywords

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

Abbreviations

AIP

Autoimmune pancreatitis

ANA

Anti-nuclear antibody

CA-II

Carbonic anhydrase-II

CTLA-4

Cytotoxic T lymphocyte antigen-4

ERCP

Endoscopic retrograde cholangio-pancreatography

FCRL

Fc-receptor-like

IFN-γ

Interferon-γ

IL-4

Interleukin-4

LF

Lactoferrin

LPSP

Lymphoplasmacytic sclerosing pancreatitis

MD

Mikulicz disease

MHC

Major histocompatibility complex

MOLPS

Multiorgan lymphoproliferative disease

PBP

Plasminogen-binding protein

SjS

Sjögren’s syndrome

PSC

Primary sclerosing cholangitis

RF

Rheumatoid factor

SIPS

Systemic IgG4 plasmacytic syndrome

SLE

Systemic lupus erythematosus

Treg

Regulatory T cell

UBR2

Ubiquitin-protein ligase E3 component n-recognin 2

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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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