M1398 Possible Role of Regulatory T Cells in Producing IgG4 in the Involved Organs With Autoimmune Pancreatitis

Abstract

Background & Aim: Autoimmune pancreatitis (AIP) is a newly recognized pancreatic disorder. Patients with AIP have several immunologic and histologic abnormalities specific to the disease, including increased levels of serum IgG4 and storiform fibrosis with infiltration of lymphocytes and IgG4-positive plasmacytes in the involved organs. Among the involved organs showing extrapancreatic lesions, bile duct is the most common, exhibiting sclerosing cholangitis (IgG4-SC). However, the role of IgG4 is unclear in the pancreas and involved organs. Recently, it has been reported that regulatory T cells (Tregs) are involved in both the development of various autoimmune diseases and the shift of B-cell toward IgG4 producing plasmacytes. For this report, we analyzed the infiltrated Tregs and IgG4-positive plasma cells in the pancreas and liver by immunohistochemistory and IL-10 producing Tregs by flowcytometry to clarify the role of IgG4 and Tregs in AIP. Subjects and Methods: The 6 AIP patients were obtained from Kansai Medical University. 6 cases of chronic pancreatitis were served as disease control. Hepatic tissue was sectioned from 16 IgG4-SC patients and 26 patients with PSC. All AIP and 14 IgG4-SC patients were diagnosed by Asian criteria. One IgG4-SC patient was diagnosed by Mayo (HISORt) criteria and other was diagnosed by biopsy. We studied infiltrating IgG4-positive cells and Tregs in the pancreas and liver by immunohistochemistry. IL-10 producing Tregs were analyzed from peripheral blood by flow cytometry. Results: In the pancreas, Tregs were increased in the pancreas with AIP (24.6±18.0 cells/HPF) compared with controls (5.1±4.3 cells/HPF). The numbers of IgG4positive plasma cells were significantly higher in AIP (18.6±10.3 cells/HPF) than in controls (1.1±0.7 cells/HPF). However, there were no significant differences in CD3+, CD4+, or CD79+ cells between the AIP (CD3: 63.1±27.1, CD4: 48.2±32.9, CD79: 24.1±9.2 cells/ HPF) and control sections (CD3: 73.6±37.1, CD4: 34.0±23.8, CD79: 14.5±14.6 cells/HPF). In the liver, the numbers of IgG4-positive plasma cells were significantly higher in IgG4SC (16.6±7.7 cells/HPF) than in PSC (4.0±0.7 cells/HPF). Tregs in the patients with IgG4SC (5.4±1.5 cells/HPF) were also significantly increased compared with PSC (2.0±0.3 cells/ HPF). In the patients with IgG4-SC, the numbers of infiltrated Tregs were significantly positively correlated with IgG4-positive plasma cells (R=0.75). In patients with the untreated AIP, IL-10 producing Tregs and IgG4 also positively correlated (R=0.53). Conclusion: In AIP, abundant infiltration of Tregs may affect the switching of B cells to IgG4-producing plasmacytes.