The role of CD19+ CD24high CD38high and CD19+ CD24high CD27+ regulatory B cells in patients with type 1 autoimmune pancreatitis.
BACKGROUND
Patients with type 1 autoimmune pancreatitis (AIP) have several immunologic and histologic abnormalities. It is known that depletion of B cells by rituximab is effective for treatment of IgG4-related disease (IgG4-RD) such as type 1 AIP, suggesting that B cells may be a key player in IgG4-RD. However, the role of regulatory B cells (Bregs) in type 1 AIP is unclear, and the objective of this paper is to clarify the role of Bregs in the pathophysiology of type 1 AIP by analyzing circulating Bregs.


METHODS
We recruited 21 patients with type 1 AIP as determined by the International Consensus Diagnostic Criteria for AIP (ICDC). No patients received corticosteroid treatments. For comparison, we recruited 14 patients with chronic pancreatitis (CP), 20 patients with pancreatic cancer, and 25 healthy subjects as controls. We analyzed Bregs as CD19+ CD24high CD38high and CD19+ CD24high CD27+ from peripheral blood by flow cytometry.


RESULTS
In peripheral blood, CD19+ CD24high CD38high Bregs were significantly increased in type 1 AIP patients compared with CP, pancreatic cancer, and healthy controls. Although not significant different, CD19+ CD24high CD27+ Bregs of type 1 AIP were decreased compared to those of other groups. IL-10(+) B cells were not significantly different from type 1 AIP patients and healthy controls. In untreated type 1 AIP patients, the number of CD19+ CD24high CD38high Bregs and IgG4 were not correlated.


CONCLUSIONS
Our data suggested that CD19+ CD24high CD38high Bregs seemed to increase reactively to suppress the disease activity, and are consistent with the hypothesis that CD19+ CD24high CD27+ Bregs might be involved in the development of type 1 AIP, although it still remains unclear whether the decrease of CD19+ CD24high CD27+ cells is cause or effect of AIP.
The Third Department of Internal Medicine, Division of Gastroenterology and Hepatology, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka 573-1191, Japan.
Kimi
K
Sumimoto
The Third Department of Internal Medicine, Division of Gastroenterology and Hepatology, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka 573-1191, Japan.
Kazushige
K
Uchida
The Third Department of Internal Medicine, Division of Gastroenterology and Hepatology, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka 573-1191, Japan.
Takeo
T
Kusuda
The Third Department of Internal Medicine, Division of Gastroenterology and Hepatology, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka 573-1191, Japan.
Toshiyuki
T
Mitsuyama
The Third Department of Internal Medicine, Division of Gastroenterology and Hepatology, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka 573-1191, Japan.
Yutaku
Y
Sakaguchi
The Third Department of Internal Medicine, Division of Gastroenterology and Hepatology, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka 573-1191, Japan.
Toshiro
T
Fukui
The Third Department of Internal Medicine, Division of Gastroenterology and Hepatology, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka 573-1191, Japan.
Mitsunobu
M
Matsushita
The Third Department of Internal Medicine, Division of Gastroenterology and Hepatology, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka 573-1191, Japan.
Makoto
M
Takaoka
The Third Department of Internal Medicine, Division of Gastroenterology and Hepatology, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka 573-1191, Japan.
Akiyoshi
A
Nishio
The Third Department of Internal Medicine, Division of Gastroenterology and Hepatology, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka 573-1191, Japan. Electronic address: okazaki@hirakata.kmu.ac.jp.
Kazuichi
K
Okazaki
D051997:ADP-ribosyl Cyclase 1 / Q000097:blood; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018941:Antigens, CD19 / Q000097:blood; D001327:Autoimmune Diseases / Q000276:immunology*; D060151:B-Lymphocytes, Regulatory / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D051927:CD24 Antigen / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016753:Interleukin-10 / Q000097:blood; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood; D008875:Middle Aged; D010195:Pancreatitis / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000097:blood
D018941:Antigens, CD19; D015415:Biomarkers; D051927:CD24 Antigen; C508609:IL10 protein, human; D008562:Membrane Glycoproteins; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D016753:Interleukin-10; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1
Interleukin-10 (IL-10); Regulatory B cells (Bregs); Type 1 autoimmune pancreatitis (AIP)