Journal of Gastroenterology

, Volume 48, Issue 6, pp 751–761 | Cite as

The similarity of Type 1 autoimmune pancreatitis to pancreatic ductal adenocarcinoma with significant IgG4-positive plasma cell infiltration

  • Yuri Fukui
  • Kazushige Uchida
  • Kimi Sumimoto
  • Takeo Kusuda
  • Hideaki Miyoshi
  • Masanori Koyabu
  • Tsukasa Ikeura
  • Yutaku Sakaguchi
  • Masaaki Shimatani
  • Toshiro Fukui
  • Mitsunobu Matsushita
  • Makoto Takaoka
  • Akiyoshi Nishio
  • Nobuaki Shikata
  • Noriko Sakaida
  • Yoshiko Uemura
  • Sohei Satoi
  • A-hon Kwon
  • Kazuichi Okazaki
Original Article—Liver, Pancreas, and Biliary Tract

Abstract

Background

High serum immunoglobulin G4 (IgG4) levels and infiltration of IgG4-positive cells are characteristic of Type 1 autoimmune pancreatitis (AIP). We previously reported that increased regulatory T cells (Tregs) may regulate IgG4 production in AIP. Although an increased serum IgG4 concentration is observed in some patients with pancreatic ductal adenocarcinoma (PDA), clarification is still necessary. We have therefore studied the correlations between IgG4-positive cells and Tregs in patients with PDA.

Subjects and methods

A total of 21 PDA and nine AIP patients were enrolled in our study. The numbers and ratios of Tregs, IgG4-positive, and IgG-positive cells immunohistochemically stained with anti-Foxp3, IgG4, and IgG antibodies, respectively, were counted in three areas of resected pancreata in PDA, peritumoral pancreatitis (PT), and obstructive pancreatitis (OP).

Results

In PDA, PT, OP area, the number of IgG4-Positive cells (5.183 ± 1.061, 2.250 ± 0.431, 4.033 ± 1.018, respectively; p < 0.05) and the ratio of IgG4/IgG (0.391 ± 0.045, 0.259 ± 0.054, 0.210 ± 0.048, respectively; p < 0.05) were significantly lower than those in AIP (21.667 ± 2.436 and 0.306 ± 0.052, respectively). The numbers of IgG4-positive cells did not differ significantly among the three areas of resected pancreata examined. However, the IgG4/IgG (0.391 ± 0.045) and Foxp3/monocyte (0.051 ± 0.008) ratios in PDA area were significantly (p < 0.05) higher than those in OP area (IgG4/IgG: 0.210 ± 0.048; oxp3/monocyte: 0.0332 ± 0.005), but not in PT area. Of the 21 cases of PDA, the ratio of IgG4/IgG was >40 % in nine (43 %), six (29 %) and three (14 %) cases in PDA, PT and OP area, respectively. Foxp3 and IgG4 were positively correlated in OP area, but not in PDA and PT area.

Conclusions

Clinicians should be careful when basing a differential diagnosis of PDA and AIP on the numbers of IgG4-positive cells and the ratio of IgG4/IgG, especially when determined using a small biopsied sample.

Keywords

Autoimmune pancreatitis IgG4 Regulatory T cells Forkhead box P3 Pancreatic ductal adenocarcinoma 

Notes

Acknowledgments

This study was partially supported by (1) Grant-in-Aid for Scientific Research (C) of the Ministry of Culture and Science of Japan (20590810, 24591020), (2) the Research Program on Intractable Diseases, from the Ministry of Labor and Welfare of Japan, and (3) grants-in-aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan, from CREST Japan Science and Technology Agency.

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer 2012

Authors and Affiliations

  • Yuri Fukui
    • 1
  • Kazushige Uchida
    • 1
  • Kimi Sumimoto
    • 1
  • Takeo Kusuda
    • 1
  • Hideaki Miyoshi
    • 1
  • Masanori Koyabu
    • 1
  • Tsukasa Ikeura
    • 1
  • Yutaku Sakaguchi
    • 1
  • Masaaki Shimatani
    • 1
  • Toshiro Fukui
    • 1
  • Mitsunobu Matsushita
    • 1
  • Makoto Takaoka
    • 1
  • Akiyoshi Nishio
    • 1
  • Nobuaki Shikata
    • 2
  • Noriko Sakaida
    • 2
  • Yoshiko Uemura
    • 2
  • Sohei Satoi
    • 3
  • A-hon Kwon
    • 3
  • Kazuichi Okazaki
    • 1
  1. 1.Division of Gastroenterology and Hepatology, The Third Department of Internal MedicineKansai Medical UniversityMoriguchiJapan
  2. 2.Department of PathologyKansai Medical UniversityMoriguchiJapan
  3. 3.Department of SurgeryKansai Medical UniversityMoriguchiJapan

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