scholarly journals Regulatory T Cells in Type 1 Autoimmune Pancreatitis

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Kazushige Uchida ◽  
Takeo Kusuda ◽  
Masanori Koyabu ◽  
Hideaki Miyoshi ◽  
Norimasa Fukata ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Autoimmune Pancreatitis ◽  
Plasma Cells ◽  
Costimulatory Molecule ◽  
International Consensus ◽  
Serum Igg4 ◽  
Storiform Fibrosis ◽  
Type 1 Autoimmune Pancreatitis

Autoimmune pancreatitis (AIP) is a newly recognized pancreatic disorder. Recently, International Consensus Diagnostic Criteria for AIP (ICDC) was published. In this ICDC, AIP was classified into Type 1 and Type 2. Patients with Type 1 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, the bile duct is the most common, exhibiting sclerosing cholangitis (IgG4-SC). However, the role of IgG4 is unclear. 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 cells toward IgG4, producing plasmacytes. Our study showed that Tregs were increased in the pancreas with Type 1 AIP and IgG4-SC compared with control. In the patients with Type 1 AIP and IgG4-SC, the numbers of infiltrated Tregs were significantly positively correlated with IgG4-positive plasma cells. In Type 1 AIP, inducible costimulatory molecule (ICOS)+and IL-10+Tregs significantly increased compared with control groups. Our data suggest that increased quantities of ICOS+Tregs may influence IgG4 production via IL-10 in Type 1 AIP.

Interleukin-35 promotes the differentiation of regulatory T cells and suppresses Th2 response in IgG4-related type 1 autoimmune pancreatitis

2020 ◽  
Vol 55 (8) ◽  
pp. 789-799 ◽  
Author(s):  
Takashi Ito ◽  
Toshihiro Tanaka ◽  
Koh Nakamaru ◽  
Takashi Tomiyama ◽  
Takashi Yamaguchi ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Autoimmune Pancreatitis ◽  
Th2 Response ◽  
Type 1 Autoimmune Pancreatitis

Immunostaining With Immunoglobulin G Subclass Antibody Cocktail for Diagnosis of Type 1 Autoimmune Pancreatitis

2020 ◽  
Vol 28 (8) ◽  
pp. 844-849
Author(s):  
Rie Nakata ◽  
Takeshi Uehara ◽  
Mai Iwaya ◽  
Shiho Asaka ◽  
Shota Kobayashi ◽  
...  
Keyword(s):  
Autoimmune Pancreatitis ◽  
Plasma Cells ◽  
Tumor Formation ◽  
Mean Values ◽  
Serum Igg4 ◽  
Type 1 Autoimmune Pancreatitis ◽  
Immunoglobulin G Subclass ◽  
Antibody Cocktail ◽  
Focal Tumor

Background. Immunoglobulin (Ig) G4-related diseases (RDs) are systemic diseases in which serum IgG4 levels are frequently elevated. They can cause diffuse or focal tumor formation, organ swelling, and tissue thickening in organs infiltrated by IgG4 + plasma cells. The diagnostic criteria for IgG4-RDs include an IgG4/IgG ratio >40%, but counting IgG+ cells can be difficult because of the weakness of IgG staining density. We hypothesized that an antibody cocktail of mixed IgG1, IgG2, IgG3, and IgG4 (AC-IgG) might give immunohistochemistry results comparable with those of IgG in IgG4-RD. Methods. We compared AC-IgG reactivity with IgG expression in type 1 autoimmune pancreatitis (AIP), a representative IgG4-RD. We compared immunohistochemistry results using AC-IgG and IgG-only in 10 cases of AIP. The coefficient of variation (Cv) was used to analyze differences between AC-IgG and IgG findings in AIP by 13 board-certified pathologists. Results. Although mean values for IgG+ cells did not significantly differ between AC-IgG (34.3; range = 27.4-37.1) and IgG (30.0; range = 23.0-45.6; P = .6254), Cv was lower for AC-IgG (33.4%) than for IgG (51.4%; regression equation; y[IgG] = 0.988 x + 0.982; correlation coefficient = 0.907). The data showed that the results of both methods were largely consistent. Conclusion. AC-IgG could replace IgG to count IgG+ cells because of its lower Cv.

Clinical Evaluation of International Consensus Diagnostic Criteria for Type 1 Autoimmune Pancreatitis in Comparison With Japanese Diagnostic Criteria 2011

Pancreas ◽  
2013 ◽  
Vol 42 (8) ◽  
pp. 1238-1244 ◽  
Author(s):  
Itaru Naitoh ◽  
Takahiro Nakazawa ◽  
Kazuki Hayashi ◽  
Katsuyuki Miyabe ◽  
Shuya Shimizu ◽  
...  
Keyword(s):  
Diagnostic Criteria ◽  
Clinical Evaluation ◽  
Autoimmune Pancreatitis ◽  
International Consensus ◽  
Type 1 Autoimmune Pancreatitis

scholarly journals Kidney Involvement in Patients with Type 1 Autoimmune Pancreatitis

2019 ◽  
Vol 8 (2) ◽  
pp. 258
Author(s):  
Miroslav Vujasinovic ◽  
Raffaella Pozzi Mucelli ◽  
Roberto Valente ◽  
Caroline Verbeke ◽  
Stephan Haas ◽  
...  
Keyword(s):  
Autoimmune Pancreatitis ◽  
Lymphocytic Infiltration ◽  
Normal Serum ◽  
International Consensus ◽  
Kidney Involvement ◽  
Type 1 Autoimmune Pancreatitis ◽  
Elevated Creatinine ◽  
Imaging Signs

Introduction: Autoimmune pancreatitis (AIP) type 1 is a special form of chronic pancreatitis with a strong lymphocytic infiltration as the pathological hallmark and other organ involvement (OOI). IgG4-related kidney disease (IgG4-RKD) was first reported as an extrapancreatic manifestation of AIP in 2004. The aim of the present study was to determine the frequency and clinical impact of kidney lesions observed in patients with AIP type 1. Methods: We performed a single-centre retrospective study on a prospectively collected cohort of patients with a histologically proven or highly probable diagnosis of AIP according to the International Consensus Diagnostic Criteria (ICDC) classification. Results: Seventy-one patients with AIP were evaluated. AIP type 1 was diagnosed in 62 (87%) patients. Kidney involvement was present in 17 (27.4%) patients with AIP type 1: 15 (88.2%) males and 2 (11.8%) females. Laboratory and/or imaging signs of kidney involvement were presented at the time of AIP diagnosis in eight (47.1%) patients. In other patients, the onset of kidney involvement occurred between four months and eight years following diagnosis. At the time of the diagnosis of kidney involvement, eight (47.1%) patients showed elevated creatinine, and nine (52.9%) patients showed normal serum creatinine. None of the patients were treated with dialysis. Conclusions: IgG4-RKD was present in 27.4% of patients with AIP type 1, with male gender predominance. In cases of early diagnosis and cortisone treatment, the clinical course was mild in most cases. Regular laboratory control of renal function should be a part of the follow-up of patients with AIP type 1.

scholarly journals Identification of serum IFN-α and IL-33 as novel biomarkers for type 1 autoimmune pancreatitis and IgG4-related disease

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Kosuke Minaga ◽  
Tomohiro Watanabe ◽  
Akane Hara ◽  
Ken Kamata ◽  
Shunsuke Omoto ◽  
...  
Keyword(s):  
Autoimmune Pancreatitis ◽  
Characteristic Curve ◽  
Elevated Serum ◽  
Normal Serum ◽  
Related Disease ◽  
Igg4 Related Disease ◽  
Number Of Patients ◽  
Serum Igg4 ◽  
Type 1 Autoimmune Pancreatitis

Abstract IgG4-related disease (IgG4-RD) is a multi-organ autoimmune disease characterized by elevated serum IgG4 concentration. Although serum IgG4 concentration is widely used as a biomarker for IgG4-RD and type 1 autoimmune pancreatitis (AIP), a pancreatic manifestation of IgG4-RD, a significant number of patients have normal serum IgG4 levels, even in the active phase of the disease. Recently, we reported that the development of experimental AIP and human type 1 AIP is associated with increased expression of IFN-α and IL-33 in the pancreas. In this study, we assessed the utility of serum IFN-α and IL-33 levels as biomarkers for type 1 AIP and IgG4-RD. Serum IFN-α and IL-33 concentrations in patients who met the diagnostic criteria for definite type 1 AIP and/or IgG4-RD were significantly higher than in those with chronic pancreatitis or in healthy controls. Strong correlations between serum IFN-α, IL-33, and IgG4 concentrations were observed. Diagnostic performance of serum IFN-α and IL-33 concentrations as markers of type 1 AIP and/or IgG4-RD was comparable to that of serum IgG4 concentration, as calculated by the receiver operating characteristic curve analysis. Induction of remission by prednisolone treatment markedly decreased the serum concentration of these cytokines. We conclude that serum IFN-α and IL-33 concentrations can be useful as biomarkers for type 1 AIP and IgG4-RD.

IgG4-related disease responder index but not serum IgG4 correlates with disease activity and the risk of 1-year relapse in type 1 autoimmune pancreatitis

Pancreatology ◽  
2019 ◽  
Vol 19 ◽  
pp. S135
Author(s):  
Filippo Vieceli ◽  
Giulia De Marchi ◽  
Antonio Amodio ◽  
Lorenzo Brozzi ◽  
Pietro Campagnola ◽  
...  
Keyword(s):  
Disease Activity ◽  
Autoimmune Pancreatitis ◽  
Related Disease ◽  
Igg4 Related Disease ◽  
Serum Igg4 ◽  
Type 1 Autoimmune Pancreatitis

scholarly journals Utility of endoscopic ultrasound-guided fine-needle biopsy in the diagnosis of type 1 autoimmune pancreatitis

2020 ◽  
Vol 08 (12) ◽  
pp. E1855-E1861
Author(s):  
Kofi W. Oppong ◽  
Pardeep Maheshwari ◽  
Manu K. Nayar ◽  
Antony Darne ◽  
Daniel Parkinson ◽  
...  
Keyword(s):  
Endoscopic Ultrasound ◽  
Autoimmune Pancreatitis ◽  
Needle Biopsy ◽  
Final Diagnosis ◽  
Fine Needle Biopsy ◽  
Pathological Feature ◽  
International Consensus ◽  
Fine Needle ◽  
Type 1 Autoimmune Pancreatitis

Abstract Background and study aims Endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) performs poorly in the histological diagnosis of type 1 autoimmune pancreatitis (AIP). The aim of this study was to assess the performance of fine-needle biopsy (FNB) comparing reverse bevel (RB) and fork-tip (FT) needles. Patients and methods A retrospective study of prospectively maintained databases was performed. Patients with a final diagnosis of type 1 AIP who underwent EUS-FNB during diagnostic workup were included. Pathology reports were reviewed and classified as per international consensus diagnostic criteria (ICDC). The Primary outcome was EUS-FNB sensitivity in diagnosing type 1 AIP. Results Between March 2011 and December 2018, 24 patients with a final diagnosis of type 1 AIP underwent FNB. Six patients underwent biopsy with the RB needle and 18 with the FT needle. Mean age (± SD) 62.2 (± 11.4), 17 (70.8 %) male. No RB samples were diagnostic compared to 14 (78 %) FT; P = 0.001; of which 13 (72 %) were level 1. In eight (44 %) of FT cases a diagnosis was not possible without histology. Initial biopsy was diagnostic in five (62.5 %) of these cases. Including repeat biopsy, seven (87 %) had a diagnosis made by FT needle. Obliterative phlebitis (44 %) was the least frequently identified pathological feature and immunoglobulin (IgG)4 + plasma cells > 10 per high power field (78 %) the most common. Conclusion The FT needle demonstrated good performance for diagnosing type 1 AIP. The results support the preferential use of this core biopsy needle for EUS pancreatic tissue sampling.

scholarly journals Can the wet suction technique change the efficacy of EUS-FNA for diagnosing autoimmune pancreatitis type 1? A prospective single-arm study

2019 ◽  
Author(s):  
Mitsuru Sugimoto ◽  
Tadayuki Takagi ◽  
Rei Suzuki ◽  
Naoki Konno ◽  
Hiroyuki Asama ◽  
...  
Keyword(s):  
Autoimmune Pancreatitis ◽  
Patient Characteristics ◽  
Needle Aspiration ◽  
P Value ◽  
The West ◽  
International Consensus ◽  
Surgical Biopsy ◽  
Lymphoplasmacytic Infiltrate ◽  
Storiform Fibrosis

Abstract Background: Other than surgical biopsy, endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is the only method for histologically diagnosing autoimmune pancreatitis (AIP). However, adequate specimens are difficult to obtain. Recently, more adequate specimens were reported to be obtained with a wet suction technique (WEST) of EUS-FNA than with the conventional method of EUS-FNA. This study aimed to histologically diagnose AIP by EUS-FNA with a WEST. Methods: Eleven patients with possible type 1 AIP between February 2016 and August 2018 underwent WEST EUS-FNA (WEST group) with four punctures with 19 or 22 G needles. As a historical control, 23 type 1 AIP patients who underwent no fewer than four punctures with 19 or 22 G needles were selected (DRY group). Patient characteristics and histological findings were compared between the two groups. Results: Three histopathological items of the International Consensus Diagnostic Criteria were significantly greater in the WEST group than the DRY group (n (%), lymphoplasmacytic infiltrate without granulocytic infiltration: 9 (81.8) vs 6 (26.1), p value=0.003, storiform fibrosis: 5 (45.5.) vs 1 (4.3), p value=0.008, abundant (>10 cells/HPF) IgG4-positive cells: 7 (63.6) vs 5 (21.7), p value=0.026). Level 1 or level 2 histopathological findings were observed more in the WEST group than in the DRY group (n (%) 8 (72.7) vs 3 (13.0), p value=0.001). Conclusions: WEST EUS-FNA was more useful than standard EUS-FNA for histologically diagnosing AIP.Trial registration: UMIN000019768Date of registration: November 12, 2015

Intraductal Tubulopapillary Epithelial Proliferation Associated with Type 1 Autoimmune Pancreatitis

2018 ◽  
Vol 27 (1) ◽  
pp. 83-87 ◽  
Author(s):  
Shinya Fujie ◽  
Hiroyuki Matsubayashi ◽  
Hirotoshi Ishiwatari ◽  
Hiromasa Hazama ◽  
Takaaki Ito ◽  
...  
Keyword(s):  
Pancreatic Duct ◽  
Autoimmune Pancreatitis ◽  
Fibrous Tissue ◽  
Ductal Adenocarcinoma ◽  
Epithelial Proliferation ◽  
Pancreatic Body ◽  
Gastric Type ◽  
Serum Igg4 ◽  
Type 1 Autoimmune Pancreatitis

A 70-year-old man was referred to our hospital with exacerbation of diabetes. His blood tests showed elevated levels of serum IgG4 and HbA1c. Computed tomography of the pancreatic body demonstrated a weakly enhanced mass, 2 cm in size, with indistinct borders. Magnetic resonance cholangiopancreatography revealed a narrowing of the main pancreatic duct (MPD) at the pancreatic body, a markedly dilated upstream duct, and a slightly dilated downstream duct. Endoscopic ultrasonography demonstrated an iso-hypoechoic heterogeneous mass, protruding and spreading in the pancreatic duct. The histology of a fine needle aspiration sample demonstrated fibrous tissue containing abundant IgG4-positive plasma cells and atypical epithelial cells. The imaging findings and histology were not typical for either pancreatic ductal adenocarcinoma or type 1 autoimmune pancreatitis (AIP), but these were not completely excluded, and a distal pancreatectomy was performed. Histological examination showed an intraductal tubulopapillary epithelial proliferation, which contained cytoplasmic mucin (MUC5AC and MUC6), and severe IgG4-positive lymphoplasmacytic infiltration in the interstitium around the MPD. Next-generation sequencing using DNA extracted from the tumor revealed no mutation of K-ras, GNAS, or TP53. The entire lesion was ultimately diagnosed as AIP with an intraductal tubular and papillary epithelial hyperplasia producing gastric-type mucin. Some recent reports have described AIP development in the background of intraductal papillary mucinous neoplasms, and some have hypothesized a paraneoplastic occurrence of IgG4-related disease. The current case indicates issues in the clinical diagnosis of rare variants of AIP, and raises questions about the relationship between AIP and pancreatic epithelial lesions.

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