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

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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.

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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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Acknowledgments

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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  1. Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, Kansai Medical University, Shinmachi, Hirakata, Osaka, 573-1197, Japan

    Kazuichi Okazaki, Kazushige Uchida, Masanori Koyabu, Hideaki Miyoshi & Makoto Takaoka

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  1. Kazuichi Okazaki
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Okazaki, K., Uchida, K., Koyabu, M. et al. Recent advances in the concept and diagnosis of autoimmune pancreatitis and IgG4-related disease. J Gastroenterol 46, 277–288 (2011). https://doi.org/10.1007/s00535-011-0386-x

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