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


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.
Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, Kansai Medical University, 10-15 Fumizono, Moriguchi, Osaka, 570-8507, Japan.
Yuri
Y
Fukui
Kazushige
K
Uchida
Kimi
K
Sumimoto
Takeo
T
Kusuda
Hideaki
H
Miyoshi
Masanori
M
Koyabu
Tsukasa
T
Ikeura
Yutaku
Y
Sakaguchi
Masaaki
M
Shimatani
Toshiro
T
Fukui
Mitsunobu
M
Matsushita
Makoto
M
Takaoka
Akiyoshi
A
Nishio
Nobuaki
N
Shikata
Noriko
N
Sakaida
Yoshiko
Y
Uemura
Sohei
S
Satoi
A-Hon
AH
Kwon
Kazuichi
K
Okazaki
D000230:Adenocarcinoma / Q000276:immunology* / Q000473:pathology*; D000368:Aged; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology*; D021441:Carcinoma, Pancreatic Ductal / Q000276:immunology* / Q000473:pathology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000276:immunology* / Q000473:pathology*; D010195:Pancreatitis / Q000145:classification / Q000276:immunology*; D010950:Plasma Cells / Q000473:pathology*
D007074:Immunoglobulin G