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Autoimmune pancreatitis—a new evolving pancreatic disease?

  • New Surgical Horizons
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Abstract

Introduction

Recent advances support the concept of autoimmune pancreatitis as a unique systemic disease because occasional extrapancreatic lesions such as sclerosing cholangitis, sclerosing sialoadenitis, and retroperitoneal fibrosis show similar pathological features with fibrosis and abundant infiltration of IgG4-positive plasma cells, and are steroid responsive. Based on these findings, several diagnostic criteria have been proposed.

Materials and methods

Although AIP is accepted worldwide as a unique clinical entity, pathogeneic mechanism still remains unclear. To clarify it, genetic background, humoral immunity, candidates of target antigens including self-antigens and molecular mimicry from microbes, cellular immunity including regulatory T cells, complement system, and experimental models are reviewed.

Results

Based on these findings, we have proposed a hypothesis for the pathogenesis of AIP in the biphasic mechanism of “induction” and “progression.” In the early stage, initial response to self-antigens (LF, CA-II, CA-IV, PSTI, or α-fodrin) or molecular mimicry (Helicobacter pylori) is induced by decreased naive regulatory T cells (Tregs), and Th1 cells release proinflammatory cytokines (IFN-γ, IL-1b, IL-2, and TNF-α).

Discussion

In the chronic stage, progression is supported by increased memory Tregs and Th2 immune responses. The classical pathway of complement system may be activated by IgG1 immune complex.

Conclusion

As Tregs seem to take important roles in progression as well as induction of the disease, further studies are necessary to clarify the pathogenesis.

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Abbreviations

Anti-CA-II:

Carbonic anhydrase II

AIP:

Autoimmune pancreatitis

LF:

Lactoferrin

AMA:

Anti-mitochondrial antibody

ANA:

Antinuclear antibody

CA-II:

Carbonic anhydrase II

ERCP:

Endoscopic retrograde cholangio-pancreatography

IFN-γ:

Interferon-γ

IL-4:

Interleukin-4

LF:

Lactoferrin

PBC:

Primary biliary cirrhosis

PSC:

Primary sclerosing cholangitis

RF:

Rheumatoid factor

SjS:

Sjögren’s syndrome

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Acknowledgments

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

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Authors and Affiliations

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

    Kazuichi Okazaki, Kazushige Uchida, Toshiro Fukui, Makoto Takaoka & Akiyoshi Nishio

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  1. Kazuichi Okazaki
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  2. Kazushige Uchida
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Correspondence to Kazuichi Okazaki.

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Okazaki, K., Uchida, K., Fukui, T. et al. Autoimmune pancreatitis—a new evolving pancreatic disease?. Langenbecks Arch Surg 395, 989–1000 (2010). https://doi.org/10.1007/s00423-010-0714-2

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