Sumimoto Kimi, Uchida Kazushige, Kusuda Takeo, Mitsuyama Toshiyuki, Sakaguchi Yutaku, Fukui Toshiro, Matsushita Mitsunobu, Takaoka Makoto, Nishio Akiyoshi, Okazaki Kazuichi
The Third Department of Internal Medicine, Division of Gastroenterology and Hepatology, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka 573-1191, Japan.
The Third Department of Internal Medicine, Division of Gastroenterology and Hepatology, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka 573-1191, Japan.
Pancreatology. 2014 May-Jun;14(3):193-200. doi: 10.1016/j.pan.2014.02.004. Epub 2014 Feb 25.
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.
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.
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.
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.
1型自身免疫性胰腺炎（AIP）患者存在多种免疫和组织学异常。已知利妥昔单抗清除B细胞对治疗IgG4相关疾病（IgG4-RD）如1型AIP有效，这表明B细胞可能是IgG4-RD的关键因素。然而，调节性B细胞（Bregs）在1型AIP中的作用尚不清楚，本文的目的是通过分析循环Bregs来阐明Bregs在1型AIP病理生理学中的作用。
我们招募了21例根据AIP国际共识诊断标准（ICDC）确定的1型AIP患者。没有患者接受过皮质类固醇治疗。为了进行比较，我们招募了14例慢性胰腺炎（CP）患者、20例胰腺癌患者和25名健康受试者作为对照。我们通过流式细胞术分析外周血中作为CD19+ CD24高 CD38高和CD19+ CD24高 CD27+的Bregs。
在外周血中，与CP、胰腺癌和健康对照相比，1型AIP患者中CD19+ CD24高 CD38高的Bregs显著增加。虽然差异不显著，但1型AIP的CD19+ CD24高 CD27+ Bregs与其他组相比有所减少。IL-10(+) B细胞在1型AIP患者和健康对照之间没有显著差异。在未经治疗的1型AIP患者中，CD19+ CD24高 CD38高的Bregs数量与IgG4不相关。
我们的数据表明，CD19+ CD24高 CD38高的Bregs似乎是为了抑制疾病活动而反应性增加，这与CD19+ CD24高 CD27+ Bregs可能参与1型AIP发生发展的假设一致，尽管CD19+ CD24高 CD27+细胞的减少是AIP的原因还是结果仍不清楚。
